Search results for: metabolism and excretion–toxicity

Authors: Bendjazia Radia, Samira Kilani-Morakchi, Nadia Aribi

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Azadirachtin is a biorational insecticide commonly reported as selective to a range of beneficial insects. It is one of the most biologically active natural inhibitors of insect growth and development and it is known to be an antagonist of the juvenile hormone and 20-hydroxyecdysone (20E). However, its mechanism of action remains still unknown. In the present study, the toxicity of a commercial formulation of Azadirachtin (Neem Azal, 1% azadirachtine) was evaluated by topical application at various doses (0.1, 0.25, 0.5, 1 and 2 µg/insect) on the third instars larvae of D. melanogaster. Lethal doses (LD25: 0.28µg and LD50: 0.67µg), were evaluated by cumulated mortality at the immature stages. The effects of azadirachtin (LD25 and LD50) were then evaluated on the development (duration of the larval and pupal instars, the weight of larvae, pupa and adults) of Drosophila melanogaster. Results showed that the insecticide increased significantly the larval and pupal instar duration. A reduction of larval and pupal weight is noted under azadirachtin treatment as compared to controls. In addition, the weight of surviving adults at the two tested dose was also reduced. In conclusion, azadirachtin seemed to interfere with the functions of the endocrine system resulting in development defects.

Keywords: azadirachtin, d.melanogaster, toxicity, development

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Authors: Mala Tankam Carine, Kekeunou Sévilor, Nukenine Elias

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Storage and preservation of agricultural products remain the only conditions ensuring the almost permanent availability of foodstuffs. However, infestations due to insects and microorganisms often occur. Callosobruchus maculatus is a pest that causes a lot of damage to cowpea stocks in the tropics. Several methods are adopted to limit their damage, but the use of synthetic chemical insecticides is the most widespread. Biopesticides in sustainable agriculture respond to several environmental, economic and social concerns while offering innovative opportunities that are ecologically and economically viable for producers, workers, consumers and ecosystems. Our main objective is to evaluate the insecticidal efficacy of binary combinations of Fossilshield with root-bark powder of Securidaca longepedunculata against Callosobruchus maculatus in stored cowpea Vigna unguiculata. Laboratory bioassays were conducted in stored grains to evaluate the toxicity of root-bark powder of Securidaca longepedunculata alone or combined with diatomaceous earth Fossil-Shield ® against C. maculatus. Twenty-hour-old adults of C. maculatus were exposed to 50g of cowpea seeds treated with four doses (10, 20, 30, and 40g/kg) of root-bark powder of S. longepedunculata, on the one hand, and (0.5, 1, 1.5, and 2 g/kg) on DE and binary combinations on the other hand. 0g/kg corresponded to untreated control. Adult mortality was recorded up to 7 days (d) post-treatment, whereas the number of F1 progeny was assessed after 30 d. Weight loss and germinative ability were conducted after 120 d. All treatments were arranged according to a completely randomized block with four replicates. The combined mixture of S. longepedunculata and DE controlled the beetle faster compared to the root-bark powder of S. longepedunculata alone. According to the Co-toxicity coefficient, additive effect of binary combinations was recorded at 3-day post-exposure time with the mixture 25% FossilShield + 75% S. longepedunculata. A synergistic action was observed after 3-d post-exposure at mixture 50% FossilShield + 50% S. longepedunculata and at 1-d and 3-d post-exposure periods at mixture 75% FossilShield + 25% S. longepedunculata. The mixture 25% FossilShield + 75% S. longepedunculata induced a decreased progeny of 6 times fewer individuals for 4.5 times less weight loss and 2, 9 times more sprouted grains than with root-bark powder of S. longepedunculata. The combination of FossilShield + S. longepedunculata was more potent than root-bark powder of S. longepedunculata alone, although the root-bark powder of S. longepedunculata caused significant reduction of F1 adults compared to the control. Combined action of botanical insecticides with FossilShield as a grain protectant in an integrated pest management approach is discussed.

Keywords: diatomaceous earth, cowpea, callosobruchus maculatus, securidaca longepedunculata, combined action, co-toxicity coefficient

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C. W. Tang, Lemin Zheng, Min Chen

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Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established an alternative principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Yogesh Bacchaw, Ashish Dabade

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Nowadays oral health is raising concern in society. Acid producing microorganisms changes the oral pH and creates a favorable environment for microbial growth. This growth not only promotes dental decay but also bad breath. Generally Recognized As Safe (GRAS) listed component was incorporated in chewing gum as an antimicrobial agent. The chewing gum produced exhibited up to 9 hours of antimicrobial activity against oral microflora. The toxicity of GRAS component per RACC value of chewing gum was negligible as compared to actual toxicity level of GRAS component. The antibacterial efficiency of chewing gum was tested by using total plate count (TPC) and colony forming unit (CFU). Nine hours were required to microflora to reach TPC/CFU of before chewing gum consumption. This chewing gum not only provides mouth freshening activity but also helps in lowering dental decay, bad breath, and enamel whitening.

Keywords: colony forming unit (CFU), chewing gum, generally recognized as safe (GRAS), microbial growth, microorganisms, oral health, RACC, total plate count (TPC), antimicrobial agent, enamel whitening, oral pH

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Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

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The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.

Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity

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Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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Authors: Chaoge Wang, Xiquan Weng, Yan Meng, Wentao Lin

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Objective: Cold exposure and exercise serve as two physiological stimuli to glycolipid metabolism and insulin sensitivity. So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting glycolipid metabolism and insulin sensitivity. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and sucessfully to establish an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), acute clod control group (AC), acute cold exercise group (AE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; for acute cold exposure, the rats were exposed to cold for only 4h before the end of the experiment; for intermittent cold exposure, the rats were exposed to cold for 4h per day. The protocol for treadmill runnings were as follows: 25m/min (speed), 0°C (slope), 30 mins each time, an interval for 10 mins between two runnings, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. Blood lipids, free fatty acids, blood glucose (FBG), and serum insulin (FINS) were examined, and the insulin resistance index (HOMA-IR = FBG (mmol/L)×FINS(mIU/L)/22.5) was calculated. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (p < 0.05 was significant). Results: (1) Compared with the NC group, the FBG of the rats was significantly declined in the NE, CE, AC, AE, and IE groups (p < 0.05), the FINS of the rats was significantly declined in the AE group (p < 0.05), the HOMA-IR of the rats was significantly declined in the NE, CE, AC, AE and IE groups (p < 0.05). Compared with the NE group, the FBG of the rats was significantly declined in the CE, AE, and IE groups (p < 0.05), the FINS and HOMA-IR of the rats were significantly declined in the AE group (p < 0.05). (2) Compared with the NC group, the CHO, TG, LDL-C, and FFA of the rats were significantly declined in CE and IE groups (p < 0.05), the HDL-C of the rats was significantly higher in NE, CC, CE, AE, and IE groups (p < 0.05). Compared with the NE group, the HDL-C of the rats was significantly higher in the CE and IE groups (p < 0.05). Conclusions: Sedentariness or exercise in the acute cold doesn't make sense in the treatment of type 2 diabetes, which led to one-off increases of the body's insulin sensitivity. Exercise in the continuous and intermittent cold can effectively decline the FBG, TC, TG, LDL-C, and FFA levels and increase the HDL-C level and insulin sensitivity in obese rats. These results can impact the prevention and treatment of type 2 diabetes.

Keywords: cold, exercise, insulin sensitivity, obesity

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Authors: Pui Shan Wong, Kosuke Tashiro, Satoru Kuhara, Sachiyo Aburatani

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Functional genomics and gene regulation inference has readily expanded our knowledge and understanding of gene interactions with regards to expression regulation. With the advancement of transcriptome sequencing in time-series comes the ability to study the sequential changes of the transcriptome. This method presented here works to augment existing regulation networks accumulated in literature with transcriptome data gathered from time-series experiments to construct a sequential representation of transcription factor activity. This method is applied on a time-series RNA-Seq data set from Escherichia coli as it transitions from growth to stationary phase over five hours. Investigations are conducted on the various metabolic activities in gene regulation processes by taking advantage of the correlation between regulatory gene pairs to examine their activity on a dynamic network. Especially, the changes in metabolic activity during phase transition are analyzed with focus on the pagP gene as well as other associated transcription factors. The visualization of the sequential transcriptional activity is used to describe the change in metabolic pathway activity originating from the pagP transcription factor, phoP. The results show a shift from amino acid and nucleic acid metabolism, to energy metabolism during the transition to stationary phase in E. coli.

Keywords: Escherichia coli, gene regulation, network, time-series

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Authors: Alemu Tadesse Feroche

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In this study, some 2, 3 distributed quinazoline -4 (3H) - one derivative were synthesized using a three-step synthetic route. They were obtained in a good yield (59.5-85%) by applying different chemical reactions like cyclization and condensation reactions. The chemical structure of the final compounds was also verified by spectroscopic methods (IR, ¹HNMR) and elemental microanalysis. The in vivo antimalarial activity of these compounds on P. berghei infected mice was found to be moderate to high at an oral dose of 0.04846 mmol/kg /day. This is equal to 25 mg/kg of chloroquine phosphate, which causes 100% inhibition of the parasite. It is worth mentioning that most active compounds (E) -3 Phenyl -2- [2- (pyridine -4- yl) vinyl] -4 (3H) -quinazolinone IVa (64.02%, (E)-2-[2-(4 - Hydroxy-3 - methoxystyryl) - vinyl) -3 - phenyl -4 (3H ) - quinazolinone IVc (77.25%) and (E)-2 –[2 –(Pyridin -4-yl) –vinyl] -3 phenenylamine -4(3H) quinazolinone IVe (73.54%) showed a dose-dependent increase in present suppression in antimalarial activities. Furthermore, the synthesized compounds were screened for their in vitro antileishmanial activity against L. aethiopica isolate (CL/039/09). All tested compounds (IVa (0.03766 ug/ml), IVb (0.00538 ug/ml, IVc (0.00412 ug/ml, IVd (0.00110 ug/ml), IVe (0.03017 ug/ml) and IVf (0.03894 ug/ml)) showed excellent potency that is much better than amphotericin B (IC50 = 0,04359 ug/ml). The results of acute toxicity indicated that all test compounds (IVa –IVf) proved to be nontoxic and well tolerated by the experimental animals up to 300 mg/kg in oral and 140 mg/kg in parental studies.

Keywords: 4(3H)-quinazolinone, in vivo antimalarial activity, in vitro antileishmanial activity, acute toxicity

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Authors: Komal Saini, S. K. Sahoo, B. S. Bajwa

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The Laser Fluorimetery Technique has been used for the microanalysis of uranium content in water samples collected from different sources like the hand pumps, tube wells in the drinking water samples of SW & NE Punjab, India. The geographic location of the study region in NE Punjab is between latitude 31.21º- 32.05º N and longitude 75.60º-76.14º E and for SW Punjab is between latitude 29.66º-30.48º N and longitude 74.69º-75.54º E. The purpose of this study was mainly to investigate the uranium concentration levels of ground water being used for drinking purposes and to determine its health effects, if any, to the local population of these regions. In the present study 131 samples of drinking water collected from different villages of SW and 95 samples from NE, Punjab state, India have been analyzed for chemical and radiological toxicity. In the present investigation, uranium content in water samples of SW Punjab ranges from 0.13 to 908 μgL−1 with an average of 82.1 μgL−1 whereas in samples collected from NE- Punjab, it ranges from 0 to 28.2 μgL−1 with an average of 4.84 μgL−1. Thus, revealing that in the SW- Punjab 54 % of drinking water samples have uranium concentration higher than international recommended limit of 30 µgl-1 (WHO, 2011) while 35 % of samples exceeds the threshold of 60 µgl-1 recommended by our national regulatory authority of Atomic Energy Regulatory Board (AERB), Department of Atomic Energy, India, 2004. On the other hand in the NE-Punjab region, none of the observed water sample has uranium content above the national/international recommendations. The observed radiological risk in terms of excess cancer risk ranges from 3.64x10-7 to 2.54x10-3 for SW-Punjab, whereas for NE region it ranges from 0 to 7.89x10-5. The chemical toxic effect in terms of Life-time average Daily Dose (LDD) and Hazard Quotient (HQ) have also been calculated. The LDD for SW-Punjab varies from 0.0098 to 68.46 with an average of 6.18 µg/ kg/day whereas for NE region it varies from 0 to 2.13 with average 0.365 µg/ kg/day, thus indicating presence of chemical toxicity in SW Punjab as 35% of the observed samples in the SW Punjab are above the recommendation limit of 4.53 µg/ kg/day given by AERB for 60 µgl-1 of uranium. Maximum & Minimum values for hazard quotient for SW Punjab is 0.002 & 15.11 with average 1.36 which is considerably high as compared to safe limit i.e. 1. But for NE Punjab HQ varies from 0 to 0.47. The possible sources of high uranium observed in the SW- Punjab will also be discussed.

Keywords: uranium, groundwater, radiological and chemical toxicity, Punjab, India

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Authors: Anamarel Medina-Hernandez, Teresa Ponce-Noyola, Ileana Vera-Reyes, Ana C. Ramos-Valdivia

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Somatic embryos reproduce original seed characteristics and could be implemented in biotechnological studies. Jatropha curcas L. is an important plant for biodiesel production, but also is used in traditional medicine. Seeds from J. curcas are toxic because contain diterpenoids called phorbol esters, but in Mexico exist a non-toxic variety. Therefore, somatic embryos suspension cultures from non-toxic J. curcas variety were induced. In order to investigate the characteristics of somatic embryos, a differential proteomic analysis was made between pre-globular and globular stages by 2-D gel electrophoresis. 108 spots were differentially expressed (p<0.02), and 20 spots from globular somatic embryos were sequenced by MALDI-TOF-TOF mass spectrometry. A comparative analysis of terpenoids production between the two stages was made by RP-18 TLC plates. The sequenced proteins were related to energy production (68%), protein destination and storage (9%), secondary metabolism (9%), signal transduction (5%), cell structure (5%) and aminoacid metabolism (4%). Regarding terpenoid production, in pre-globular and globular somatic embryos were identified sterols and triterpenes of pharmacological interest (alpha-amyrin and betulinic acid) but also it was found compounds that were unique to each stage. The results of this work are the basis to characterize at different levels the J. curcas somatic embryos so that this system can be used efficiently in biotechnological processes.

Keywords: Jatropha curcas, proteomics, somatic embryo, terpenoids

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Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah

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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.

Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate

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Authors: Antonina A. Shumakova, Sergey A. Khotimchenko

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The relevance of research is associated, on the one hand, with an ever-increasing volume of production and the expansion of the scope of application of engineered nanomaterials (ENMs), and on the other hand, with the lack of sufficient scientific information on the nature of the interactions of nanoparticles (NPs) with components of biogenic and abiogenic origin. In particular, studying the effect of ENMs (TiO2 NPs, SiO2 NPs, Al2O3 NPs, fullerenol) on the toxicometric characteristics of common contaminants such as lead and cadmium is an important hygienic task, given the high probability of their joint presence in food products. Data were obtained characterizing a multidirectional change in the toxicity of model toxicants when they are co-administered with various types of ENMs. One explanation for this fact is the difference in the adsorption capacity of ENMs, which was further studied in in vitro studies. For this, a method was proposed based on in vitro modeling of conditions simulating the environment of the small intestine. It should be noted that the obtained data are in good agreement with the results of in vivo experiments: - with the combined administration of lead and TiO2 NPs, there were no significant changes in the accumulation of lead in rat liver; in other organs (kidneys, spleen, testes and brain), the lead content was lower than in animals of the control group; - studying the combined effect of lead and Al2O3 NPs, a multiple and significant increase in the accumulation of lead in rat liver was observed with an increase in the dose of Al2O3 NPs. For other organs, the introduction of various doses of Al2O3 NPs did not significantly affect the bioaccumulation of lead; - with the combined administration of lead and SiO2 NPs in different doses, there was no increase in lead accumulation in all studied organs. Based on the data obtained, it can be assumed that at least three scenarios of the combined effects of ENMs and chemical contaminants on the body: - ENMs quite firmly bind contaminants in the gastrointestinal tract and such a complex becomes inaccessible (or inaccessible) for absorption; in this case, it can be expected that the toxicity of both ENMs and contaminants will decrease; - the complex formed in the gastrointestinal tract has partial solubility and can penetrate biological membranes and / or physiological barriers of the body; in this case, ENMs can play the role of a kind of conductor for contaminants and, thus, their penetration into the internal environment of the body increases, thereby increasing the toxicity of contaminants; - ENMs and contaminants do not interact with each other in any way, therefore the toxicity of each of them is determined only by its quantity and does not depend on the quantity of another component. Authors hypothesized that the degree of adsorption of various elements on the surface of ENMs may be a unique characteristic of their action, allowing a more accurate understanding of the processes occurring in a living organism.

Keywords: absorption, cadmium, engineered nanomaterials, lead

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Authors: Kayla Fanning

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Theocritus’ use of near-pastoral motifs in creating the lamenting narrative in “The Sorceress” idyll suggests a link between Simaetha and the quintessential shepherd that ultimately transcends the bucolic serenading structure, evident in “The Serenade”, as it pertains to depictions of women. In Theocritus’ “The Serenade”, an anonymous goatherd serenades his beloved, Amaryllis, in hopes of persuading her to reciprocate his love. This serenade soon turns into a vicious lament where all hope for reciprocation dissolves, leaving the goatherd severely melancholic and malignant. In “The Cyclops’ Serenade”, the cyclops, Polyphemus, sings of Galatea in solitude; in so doing, he negotiates between feelings of heartache and anger that eventually subside. His depiction of Galatea, in being less vindictive than the goatherd’s, manifests less toxicity. In adopting, and essentially creating, this serenading structure, Theocritus illustrates his ability to alter portrayals of women while maintaining the premise of the pastoral serenade; that is the shepherd's lament of his indifferent beloved. A thematic intertextual analysis of the idylls reveals a variety of ways in which the toxicity of the goatherd’s relation to Amaryllis is mutated or even inverted. In “The Sorceress”, a powerful witch named Simaetha spellbinds her unfaithful lover and angrily laments his betrayal in a way that is reminiscent of the goatherd's harmful behavior towards Amaryllis.

Keywords: femininity, pastoral, serenade, Theocritus

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Authors: Syeda Hira, Muhammad Gulfraz

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Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.

Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers

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Authors: Tomas Makaras

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Sticklebacks (Gasterosteiformes) are increasingly used in ecological and evolutionary research and become well-established role as model species for biologists. However, ecotoxicology studies concerning behavioural effects in sticklebacks regarding stress responses, mainly induced by chemical mixtures, have hardly been addressed. Moreover, although many authors in their studies emphasised the similarity between three-spined and nine-spined stickleback in morphological, neuroanatomical and behavioural adaptations to environmental changes, several comparative studies have revealed considerable differences between these species in and their susceptibility and resistance to variousstressors in laboratory experiments. The hypothesis of this study was that three-spined and nine-spined stickleback species will demonstrate apparent differences in response patterns and sensitivity to metal-based chemicals stimuli. For this purpose, we investigated the swimming behaviour (including mortality rate based on 96-h LC50 values) of two ecologically similar three-spined (Gasterosteusaculeatus) and nine-spined sticklebacks (Pungitiuspungitius) to short-term (up to 24 h) metal mixture (MIX) exposure. We evaluated the relevance and efficacy of behavioural responses of test species in the early toxicity assessment of chemical mixtures. Fish exposed to six (Zn, Pb, Cd, Cu, Ni and Cr) metals in the mixture were either singled out by the Water Framework Directive as priority or as relevant substances in surface water, which was prepared according to the environmental quality standards (EQSs) of these metals set for inland waters in the European Union (EU) (Directive 2013/39/EU). Based on acute toxicity results, G. aculeatus found to be slightly (1.4-fold) more tolerant of MIX impact than those of P. pungitius specimens. The performed behavioural analysis showed the main effect on the interaction between time, species and treatment variables. Although both species exposed to MIX revealed a decreasing tendency in swimming activity, these species’ responsiveness to MIX was somewhat different. Substantial changes in the activity of G. aculeatus were established after 3-h exposure to MIX solutions, which was 1.43-fold lower, while in the case of P. pungitius, 1.96-fold higher than established 96-h LC50 values for each species. This study demonstrated species-specific differences in response sensitivity to metal-based water pollution, indicating behavioural insensitivity of P. pungitiuscompared to G. aculeatus. While many studies highlight the usefulness and suitability of nine-spined sticklebacks for evolutionary and ecological research, attested by their increasing popularity in these fields, great caution must be exercised when using them as model species in ecotoxicological research to probe metal contamination. Meanwhile, G. aculeatus showed to be a promising bioindicator species in the environmental ecotoxicology field.

Keywords: acute toxicity, comparative behaviour, metal mixture, swimming activity

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Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: Roberta Pecoraro, Elena Maria Scalisi

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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

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Authors: Chia-Jung Li, Kuan-Hao Tsui

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As women age, the quality of their oocytes deteriorates irreversibly, leading to reduced fertility. To better understand the role of Ferroptosis-related genes in ovarian aging, we employed a multi-omics analysis approach, including spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsies. Our study identified excess lipid peroxide accumulation in aging germ cells, metal ion accumulation via oxidative reduction, and the interaction between ferroptosis and cellular energy metabolism. We used multi-histological prediction of ferroptosis key genes to evaluate 75 patients with ovarian aging insufficiency and then analyzed changes in hub genes after supplementing with DHEA, Ubiquinol CoQ10, and Cleo-20 T3 for two months. Our results demonstrated a significant increase in TFRC, GPX4, NCOA4, and SLC3A2, which were consistent with our multi-component prediction. We theorized that these supplements increase the mitochondrial tricarboxylic acid cycle (TCA) or electron transport chain (ETC), thereby increasing antioxidant enzyme GPX4 levels and reducing lipid peroxide accumulation and ferroptosis. Overall, our findings suggest that supplementation intervention significantly improves IVF outcomes in senescent cells by enhancing metal ion and energy metabolism and enhancing oocyte quality in aging women.

Keywords: multi-omics, nutrients, ferroptosis, ovarian aging

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: F. Haddadj, F. Acheuk, S. Hamdi, S. Zenia, A. Smai, H. Saadi, B. Doumandji-Mitiche

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Locust is causing significant losses in agricultural production in the countries concerned by the invasion. Up to the present control strategy has consisted only of the spreaders chemicals; they have proven harmful to the environment and. For this, a new control method appeared it comes to the biological control based mostly by using microorganism. It is in that sense is we've made our contribution by the use of a biopesticide which is entomopathogenic fungus Metarhizium anisopliae var acridium "Green Muscle" on part of the cuticule the larval of fifth instar locust Schistocerca gregaria (Forskål, 1775). Preliminary test on the study of the pathogenicity of M. anisopliae var acridium biocontrol agent, was conducted in the laboratory on L5 S. gregaria, on which we inoculated treatment in the digestive tract and it administrant 20μl of entomopathogenic solution orally at a dose DL50 = 3.25 x107 sp./ ml (median lethal dose estimated at earlier), 5 days after treatment individuals are sacrificed. After dissection cuticles are recovered and then subjected to histological sections. The histological technique followed is that of Martoja Martoja-Pierson (1967). Microscopic observation revealed alterations in the architecture of the cuticule which leads to disorganization of cell layers.

Keywords: biopesticide, cuticle, desert locust, toxicity

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Authors: Jay Ananth

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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.

Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development

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Authors: E. A. Abdel-Hakim

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The corn stemborer Sesamia cretica (Lederer), has been viewed in many parts of the world as a major pest of cultivated maize, graminaceous crops and sugarcane. Its life cycle is comprised of two different phases, one is the growth and developmental phase (non-diapause) and the other is diapause phase which takes place at the last larval instar. Several problems associated with the use of conventional insecticides, have strongly demonstrated the need for applying alternative safe compounds. Prominent among the prototypes of such prospective chemicals are the juvenoids; i.e. the insect (JH) mimics. In fact, the hormonal effect on metabolism has long been viewed as a secondary consequence of its direct action on specific energy-requiring biosynthetic mechanisms. Therefore, the present study was undertaken essentially in a rather systematic fashion as a contribution towards clarifying metabolic and energetic changes taking place during non-diapause wandering larvae as regulated by (JH) mimic. For this purpose, we applied two different doses of JH mimic (Ro 11-0111) in a single (standard) dose of 100µg or in a single dose of 20 µg/g bw in1µl acetone topically at the onset of nondiapause wandering larvae (WL). Energetic data were obtained by indirect calorimetry methods by conversion of respiratory gas exchange volumetric data, as measured manometrically using a Warburg constant respirometer, to caloric units (g-cal/g fw/h). The findings obtained can be given in brief; these treated larvae underwent supernumerary larval moults. However, this potential the wandering larvae proved to possess whereby restoration of larval programming for S. cretica to overcome stresses even at this critical developmental period. The results obtained, particularly with the high dose used, show that 98% wandering larvae were rescued to survive up to one month (vs. 5 days for normal controls), finally the formation of larval-adult intermediates. Also, the solvent controls had resulted in about 22% additional, but stationary moultings. The basal respiratory metabolism (O2 uptake and CO2 output) of the (WL), whether un-treated or larvae not had followed reciprocal U-shaped curves all along of their developmental duration. The lowest points stood nearly to the day of prepupal formation (571±187 µl O2/gfw/h and 553±181 µl CO2/gfw/h) during un-treated in contrast to the larvae treated with JH (210±48 µl O2/gfw/h and 335±81 µl CO2/gfw/h). Un-treated (normal) larvae proved to utilize carbohydrates as the principal source for energy supply; being fully oxidised without sparing any appreciable amount for endergonic conversion to fats. While, the juvenoid-treated larvae and compared with the acetone-treated control equivalents, there existed no distinguishable differences between them; both had been observed utilising carbohydrates as the sole source of energy demand and converting endergonically almost similar percentages to fats. The overall profile, treated and un-treated (WL) utilized carbohydrates as the principal source for energy demand during this stage.

Keywords: juvenile hormone, respiratory metabolism, Sesamia cretica, wandering phase

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Authors: Carolin Anna Joy, Rohith K. R, Rehin Sulay, Parvathy Santhoshkumar, G.Anil Kumar, Vibin Ipe Thomas

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Ullmann coupling reactions are gaining great relevance owing to their contribution in the synthesis of biologically and pharmaceutically important compounds. Palladium and many other heavy metals have proven their excellent ability in coupling reaction, but the toxicity matters. The first-row transition metal also possess toxicity, except in the case of iron and manganese. The suitability of manganese as a catalyst is achieving great interest in oxidation, reduction, C-H activation, coupling reaction etc. In this presentation, we discuss the thermo chemistry of ligand free manganese catalyzed C-O coupling reaction between phenol and aryl halide for the synthesis of biaryl ethers using Density functional theory techniques. The mechanism involves an oxidative addition-reductive elimination step. The transition state for both the step had been studied and confirmed using Intrinsic Reaction Coordinate (IRC) calculation. The barrier height for the reaction had also been calculated from the rate determining step. The possibility of other mechanistic way had also been studied. To achieve further insight into the mechanism, substrate having various functional groups is considered in our study to direct their effect on the feasibility of the reaction.

Keywords: Density functional theory, Molecular Modeling, ligand free, biaryl ethers, Ullmann coupling

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Authors: Shilpi Malik, Ramneek Kaur, Archita Gupta, Deepshikha Yadav, Ashwani Mathur, Manisha Singh

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Glucosamine (GS) is the most abundant naturally occurring amino monosaccharide and is normally produced in human body via cellular glucose metabolism. It is regarded as the building block of cartilage matrix and is also an essential component of cartilage matrix repair mechanism. Besides that, it can also be explored for its prebiotic potential as many bacterial species are known to utilize the amino sugar by acquiring them to form peptidoglycans and lipopolysaccharides in the bacterial cell wall. Glucosamine can therefore be considered for its fermentation by bacterial species present in the gut. Current study is focused on exploring the potential of glucosamine as prebiotic. The studies were done to optimize considerable concentration of GS to reach GI tract and being fermented by the complex gut microbiota and food grade GS was added to various Simulated Fluids of Gastro-Intestinal Tract (GIT) such as Simulated Saliva, Gastric Fluid (Fast and Fed State), Colonic fluid, etc. to detect its degradation. Since it was showing increase in microbial growth (CFU) with time, GS was Further, encapsulated to increase its residential time in the gut, which exhibited improved resistance to the simulated Gut conditions. Moreover, prepared microspehres were optimized and characterized for their encapsulation efficiency and toxicity. To further substantiate the prebiotic activity of Glucosamine, studies were also performed to determine the effect of Glucosamine on the known probiotic bacterial species, i.e. Lactobacillus delbrueckii (MTCC 911) and Bifidobacteriumbifidum (MTCC 5398). Culture conditions for glucosamine will be added in MRS media in anaerobic tube at 0.20%, 0.40%, 0.60%, 0.80%, and 1.0%, respectively. MRS media without GS was included in this experiment as the control. All samples were autoclaved at 118° C for 15 min. Active culture was added at 5% (v/v) to each anaerobic tube after cooling to room temperature and incubated at 37° C then determined biomass and pH and viable count at incubation 18h. The experiment was completed in triplicate and the results were presented as Mean ± SE (Standard error).The experimental results are conclusive and suggest Glucosamine to hold prebiotic properties.

Keywords: gastro intestinal tract, microspheres, peptidoglycans, simulated fluid

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Dalia Jomehpour, Sara Sheikhlary, Esmaeil Heydari, Mohammad Hossien Majles Ara

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In this study, we report fulvic acid-coated iron oxide nanoparticles of 10.7 ± 2.7 nm size, which serve to inhibit amyloid fibrillation formation. Although the effect of fulvic acid on tau fibrils was investigated, to our best knowledge, its inhibitory impacts on amyloid aggregation formation have been assessed neither in-vitro nor in-vivo. On the other hand, iron oxide nanoparticles exhibit anti-amyloid activity on their own. This study investigates the inhibitory effect of fulvic acid coated iron oxide nanoparticles on amyloid aggregations formed from the commonly used in-vitro model, lysozyme from chicken egg white. FESEM, XRD, and FTIR characterization confirmed that fulvic acid was coated onto the surface of the nanoparticles. The inhibitory effects of the fulvic acid coated iron oxide nanoparticles were verified by Thioflavin T assay, circular dichroism (CD), and FESEM analysis. Furthermore, the toxicity of the nanoparticles on the neuroblastoma SH-SY5Y human cell line was assessed through an MTT assay. Our results indicate that fulvic acid coated iron oxide nanoparticles can efficiently inhibit the formation of amyloid aggregations while exhibiting negligible in-vitro toxicity; thus, they can be used as anti-amyloid agents in the development of the potential drug for neurodegenerative diseases.

Keywords: Alzheimer’s disease, fulvic acid coated iron oxide nanoparticles, fulvic acid, amyloid inhibitor, polyphenols

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Authors: Jae Young Jang, Jong Hoon Ahn, Jae-Woong Lim, So Young Kang, Mi Kyeong Lee

Abstract:

Rhus verniciflua is commonly known as a lacquer tree in Korea. Stem barks of R. verniciflua have been used as an immunostimulator in traditional medicine. It contains phenolic compounds and is known for diverse biological activities such as antioxidant and antimicrobial activity. However, it also causes allergic dermatitis due to urushiols derivatives. For the development of active natural resources with less toxicity, the content of phenolic compounds and urushiols of different parts of R. verniciflua such as stem barks, lignum and leaves were quantitated by colorimetric assay and HPLC analysis. The urushiols content were the highest in stem barks, and followed by leaves. The lignum contained trace amount of urushiols. The phenolic contents, however, were the most abundant in lignum, and followed by leaves and stem barks. These results clear showed that the content of urushiols and phenolic differs depending on the parts of R. verniciflua. Antimicrobial activity of different parts of R. verniciflua against fish pathogenic bacteria was also investigated using Edwardsiella tarda. Lignum of R. verniciflua was the most effective in antimicrobial activity against E. tarda and phenolic constituents are suggested to be active constituents for activity. Taken together, phenolic compounds are responsible for antimicrobial activity of R. verniciflua. The lignum of R. verniciflua contains high content of phenolic compounds with less urushiols, which suggests efficient antimicrobial activity with less toxicity. Therefore, lignum of R. verniciflua are suggested as good sources for antimicrobial activity against fish bacterial diseases.

Keywords: different parts, phenolic compounds, Rhus verniciflua, urushiols

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Authors: Shweta Maheshwari, Anish Dua

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Hematological changes reflect the adverse effects of heavy metals on fish. Hematology is a valuable tool to evaluate pathological condition of the fish. It helps in diagnosing the structural and functional status of fish exposed to toxicants. Morphological alteration in erythrocytes due to environmental stress can be studied through ultra-structural analysis. The aim of the present study was to assess the toxicity of mercuric chloride on red blood cells of an air breathing fish, Channa punctatus. Fish were subjected to chronic experiments using three sublethal concentration of mercuric chloride (0.020mg/L, 0.027mg/L, 0.040mg/L) for a period of 15, 30 and 60 days. Exposed fish of all the three concentrations were subjected to a recovery period of 30 days. A control was maintained in tap water simultaneously. For SEM analysis, blood from caudal vein of fish was taken and examined at an accelerating voltage of 20kV. Scanning electron micrographs revealed elliptical shaped erythrocytes of control fish. Alterations in the erythrocyte morphology such as presence of spherocytes, membrane internalization, crenation of membrane and development of lobopodial projections were observed in the exposed fish. The study revealed that ultra-structural analysis appears to be a sensitive method to evaluate the toxicity of various toxicants to fish.

Keywords: Channa punctatus, erythrocytes, mercuric chloride, scanning electron microscopy

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Authors: Dagim Ali Hussen, Adnan A. Bekhit, Ariaya Hymete

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In this study, several pyridine derivatives were synthesized and evaluated for their in vitro antimicrobial activity against gram-positive bacteria (S. aureus and B. Cereus), gram-negative bacteria (P. aeruginosa and E. coli) and fungus (C. albican and A niger). The intermediate chalcone derivative 2a,b was synthesized by condensation of pyrazole aldehydes 1a,b with acetophenone in alcoholic KOH. Cyclization of 2a,b with ethyl cyanoacetate ad ammonium acetate resulted in pyridine carbonitrile derivatives 3a,b. Furthermore, condensation of pyridine-4-carboxaldeyhe with different amino-derivatives gave rise to pyridine derivatives 5a,b, 6a,b. The oxadiazole derivative 7a was prepared by cyclization of 6a with acetic anhydride. Characterization of the synthesized compound was performed using IR, 1H NMR, 13C NMR spectra and elemental microanalyses. The antimicrobial results revealed that compounds 5a, 6b and 7a exhibited half fold antibacterial activity compared to ampicillin, against B. cereus. On the other hand, compound 3b showed an equivalent activity compared to miconazole against candida albican (CANDAL 03) and to clotrimazole against the clinical isolate candida albican 6647. Moreover, this compound 3b was further tested for its acute toxicity profile. The results showed that oral LD50 is more that 300 mg/kg and parentral LD50 is more than 100 mg/kg. Compound 3b is a good candidate for antifungal agent with good toxicity profile, and deserves more chemical derivatization and clinical study.

Keywords: antifungal, antimicrobial, Candida albican, pyridine

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