Search results for: glutathione reductase activity

Authors: Yomna Ibrahim El-Gazzar, Hussien Ibrahim El-Subbagh, Hanan Hanaa Georgey, Ghada S. Hassan Hassan

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Dihydrofolate reductase (DHFR) is an enzyme that has pivotal importance in biochemistry and medicinal chemistry. It catalyzes the reduction of dihydrofolate to tetrahydrofolate and intimately couples with thymidylate synthase. Thymidylate synthase is a crucial enzyme that catalyzes the reductive methylation of (dUMP) to (dTMP) utilizing N5, N10-methylenetetrahydrofolate as a cofactor. A new series of 2-substituted thio-quinazolin-4-one analogs was designed that possessed electron withdrawing or donating functional groups (Cl or OCH3) at position 6- or 7-, 4-methoxyphenyl function at position 3-.The thiol function is used to connect to either 1,2,4-triazole, or 1,3,4-thiadiazole via a methylene bridge. Most of the functional groups designed to be accommodated on the quinazoline ring such as thioether, alkyl to increase lipid solubility of polar compounds, a character very much needed in the nonclassical DHFR inhibitors. The target compounds were verified with spectral data and elemental analysis. DHFR inhibitions, as well as antitumor activity, were applied on three cell lines (MCF-7, CACO-2, HEPG-2).

Keywords: nonclassical antifolates, DHFR Inhibitors, antitumor activity, quinazoline ring

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Authors: Bouaziz H., Soudania N., Essafia M., Ben Amara I., Hakim A., Jamoussi K., Zeghal Km, Zeghal N.

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In this investigation, we have evaluated the effects of arsenic trioxide on hepatic function in pregnant and lactating Swiss albino mice and their suckling pups. Experiments were carried out on female mice given 175 ppm As2O3 in their drinking water from the 14th day of pregnancy until day 14 after delivery. Our results showed a significant decrease in plasma levels of total protein and albumin, cholesterol and triglyceride in As2O3 treated mice and their pups. The hyperbilirubinemia and the increased plasma total alkaline phosphatase activity suggested the presence of cholestasis. Transaminase activities as well as lactate deshydrogenase activity in plasma, known as biomarkers of hepatocellular injury, were elevated indicating hepatic cells’damage after treatment with As2O3. Exposure to arsenic led to an increase of liver thiobarbituric acid reactive substances level along with a concomitant decrease in the activities of superoxide dismutase, catalase and glutathione peroxidase and in glutathione.

Keywords: antioxidant status, arsenic trioxide, hepatotoxicity, mice, oxidative stress

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Authors: Zine Kechrid

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This study was carried out to investigate the antioxidant effect of vitamin C on oxidative stress induced by dietary Zn-deficiency in albino diabetic rats. Thirty two males alloxan-diabetic rats divided into two groups of 16 individuals each; the first group was fed a zinc adequate diet (54 mg zinc/kg). The second group had given low zinc diet (1 mg zinc/kg). Then, half of each group was treated with vitamin C (1 g/l) in drinking water. After four weeks, animals were sacrificed and different parameters were determined. The findings showed that dietary deficiency zinc intake significantly increased serum glucose. Zn-deficiency was also led to an increase in oxidative stress, which was indicated by an increase of MDA level and glutathione-S-transferase activity. Meanwhile it was result in a decrease of reduced glutathione (GSH) content, glutathione peroxidase GSH-Px and catalase activities in liver. However, the administration of vitamin C restored all the previous parameters approximately to their normal values. In conclusion, vitamin C probably played a key role strong as antioxidant factor against oxidative stress provoked by dietary zinc inadequate. Therefore, it might be contributed in reduction diabetes complications.

Keywords: vitamin C, oxidative stress, zinc, experimental diabetes, rats

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Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra

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5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).

Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR

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Authors: Aneta Maćczak, Bożena Bukowska, Jaromir Michałowicz

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Bisphenols are one of the most widely used chemical compounds worldwide. They are used in the manufacturing of polycarbonates, epoxy resins and thermal paper which are applied in plastic containers, bottles, cans, newspapers, receipt and other products. Among these compounds, bisphenol A (BPA) is produced in the highest amounts. There are concerns about endocrine impact of BPA and its other toxic effects including hepatotoxicity, neurotoxicity and carcinogenicity on human organism. Moreover, BPA is supposed to increase the incidence the obesity, diabetes and heart disease. For this reason the use of BPA in the production of plastic infant feeding bottles and some other consumers products has been restricted in the European Union and the United States. Nowadays, BPA analogues like bisphenol F (BPF) and bisphenol S (BPS) have been developed as alternative compounds. The replacement of BPA with other bisphenols contributed to the increase of the exposure of human population to these substances. Toxicological studies have mainly focused on BPA. In opposite, a small number of studies concerning toxic effects of BPA analogues have been realized, which makes impossible to state whether those substituents are safe for human health. Up to now, the mechanism of bisphenols action on the erythrocytes has not been elucidated. That is why, the aim of this study was to assess the effect of BPA and its selected analogues such as BPF and BPS on the activity of antioxidant enzymes, i.e. catalase (EC 1.11.1.6.), glutathione peroxidase (E.C.1.11.1.9) and superoxide dismutase (EC.1.15.1.1) in human erythrocytes. Red blood cells in respect to their function (transport of oxygen) and very well developed enzymatic and non-enzymatic antioxidative system, are useful cellular model to assess changes in redox balance. Erythrocytes were incubated with BPA, BPF and BPS in the concentration ranging from 0.5 to 100 µg/ml for 24 h. The activity of catalase was determined by the method of Aebi (1984). The activity of glutathione peroxidase was measured according to the method described by Rice-Evans et al. (1991), while the activity of superoxide dismutase (EC.1.15.1.1) was determined by the method of Misra and Fridovich (1972). The results showed that BPA and BPF caused changes in the antioxidative enzymes activities. BPA decreased the activity of examined enzymes in the concentration of 100 µg/ml. We also noted that BPF decreased the activity of catalase (5-100 µg/ml), glutathione peroxidase (50-100 µg/ml) and superoxide dismutase (25-100 µg/ml), while BPS did not cause statistically significant changes in investigated parameters. The obtained results suggest that BPA and BPF disrupt redox balance in human erythrocytes but the observed changes may occur in human organism only during occupational or subacute exposure to these substances.

Keywords: antioxidant enzymes, bisphenol A, bisphenol a analogues, human erythrocytes

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Authors: Mustafa Kucukoduk, Evren Yildiztugay, A. Hediye Sekmen, Ismail Turkan, Yavuz Bagci

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In this study, physiological and biochemical responses of Centaurea tuzgoluensis, a Turkish endemic halophyte, to salinity were studied. Therefore, the changes in shoot growth, leaf relative water content (RWC), ion concentrations, lipid peroxidation, hydroxyl (OH.) radical scavenging activity, proline (Pro) content, and antioxidant system [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR)] were investigated. The 60 days (d) old C. tuzgoluensis seedlings were subjected to 0, 150 and 300 mM NaCl for 7 d and 14 d. The relative shoot growth was generally did not change in the 150 mM NaCl, but reduced with 300 mM NaCl stress at 7 d and 14 d. RWC was higher in 150 mM NaCl-treated leaves than that of 300 mM NaCl. Salinity decreased K+/Na+ ratio, but increased Na+, Cl, Ca+2 and Na+/Cl ratio in the leaves. On the other hand, it did not change or increase the K+ content at 150 and 300 mM NaCl, respectively. MDA content in the 150 and 300 mM NaCl-treated leaves remained close to control at 7 d. This was related to enhanced activities of SOD, CAT, APX and GR enzymes, and their isoenzymes especially Fe-SOD in the leaves. On the other hand, the higher sensitivity to 300 mM NaCl at 14 d was associated with inadequate increase in antioxidant enzymes and the decreased OH radical scavenging activity. All these results suggest that C. tuzgoluensis has different antioxidant metabolisms between short- (7 d) and long-term (14 d) salt treatments and salinity tolerance of C. tuzgoluensis might be closely related to increased capacity of antioxidative system to scavenge reactive oxygen species (ROS) and accumulation of osmoprotectant proline under salinity conditions.

Keywords: antioxidant enzymes, endemic halophyte, ion exchange, lipid peroxidation, antioxidant, enzymes, endemic halophyte, ion exchange, lipid peroxidation, proline, Centaurea tuzgoluensis

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Authors: Maryam Bordbar, Yaser Mokhayeri, Sajjad Roosta, Fatemeh Ghasemi, Saeed Choobkar, Hamidreza Nikbakht, Ebrahim Falahi

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Objective: Diabetes mellitus type 2 is the most common metabolic disorder that is growing exponentially worldwide. Satureja Khuzestanica Jamzad is a native plant of Iran that grows widely in the south of Iran. Its antimicrobial, antioxidant, anti-inflammatory and pain-relieving effects have been documented in animal studies. The purpose of this study is to investigate the effect of consumption daily S. khuzestanica on inflammatory and antioxidant indicators in type 2 diabetic patients. Methods and Materials: In a double-blind, placebo-controlled clinical trial, 67 patients with type 2 diabetes were included and divided into two groups. One group received S. khuzestanica (capsule containing 500 mg) and the other group received placebo (500 mg talcum powder) once a day for 12 weeks. After the intervention, the inflammatory and antioxidant indicators of the two groups were compared. Results: In comparison to placebo groups, there was a significant difference in levels of total antioxidant capacity, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase; these antioxidant indicators were higher in the intervention group (P<0.05). Moreover, a considerable decrease in weight, CRP and IL-6 levels were observed in patients in the S.Khuzestanica group. Conclusion: Our findings may provide novel complementary treatments without adverse effects for diabetes complications.

Keywords: Satureja khuzestanica Jamzad, diabetes mellitus, antioxidant indicators, IL-6, C-reactive protein

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Authors: Surendra Bodakhe

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In this investigation, anticataract activity was determined using cataract formation in developing chick embryo by hydrocortisone. Lenses were evaluated firstly for the extent of opacity and secondly, for lens glutathione (GSH) levels. Betulinic acid was isolated from the chloroform fraction of the crude ethanolic extract of Bauhinia variegata bark (SBE). Fourteen days old Australorp fertilized eggs were divided into different groups of six eggs each. After 24 hrs incubation in a humidified incubator (37οC), at 15 days of age; hydrocortisone (0.25µM/0.2ml/egg) was administered to the chorioallantoic membrane of chick embryos through a small hole in the egg shell on the air sack. Ascorbic acid (standard) or Betulinic acid (test) were administered at 3, 10 and 20 hr after hydrocortisone administration at a specified dose. The puncture was sealed with a cellophane tape and eggs were incubated for 48 hrs in a humidified incubator at 37οC. After 48 hrs, the lenses were isolated for the determination of the extent of opacity and Glutathione level. The betulinic acid prevented the opacification of the chick embryo lenses induced by hydrocortisone. The betulinic acid also prevented the decline of GSH content caused by hydrocortisone. The results indicate that betulinic acid protect the cataract formation in chick embryo lenses induced by hydrocortisone.

Keywords: betulinic acid, cataract, cloudiness, ovine

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Authors: Min-Ju Jo, Min-Young Um, Moonsung Choi, Sooim Shin

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Type 2 diabetes (T2D) is characterized by insulin resistance, the inability of β-cell and the dysfunction of mitochondria. To characterize effects of Cassia tora extract on mitochondrial dysfunction related T2D, the reduced glutathione level, amount of mitochondrial complexes and activities of mitochondrial complexes were measured. Three groups of mice were modeled; a control group was fed a normal diet, a diabetic group was fed a diabetic diet high in fat and carbohydrates, and a third group was fed a diabetic diet + 70% ethanol extracted Cassia tora seeds for 12 weeks. The amount of mitochondria was determined by Bradford assay after isolation of mitochondria in liver from each group. During isolation of mitochondria, cytosolic fractions of the tissue were collected to measure the reduced glutathione level. Interestingly, high level of the reduced glutathione was observed in Cassia tora treated group and decreased activities of mitochondrial complexes in Cassia tora treated group compared to the diabetic diet group. It indicates that Cassia tora has the potential to increase the reduced form of glutathione functioned as an important antioxidant in cells, and to reduce mitochondrial metabolic compensatory mechanism.

Keywords: antioxidant, Cassia tora, diabetes, electron transport chain, glutathione, mitochondria, spectrophotometry

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Authors: Alok Nahata

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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Mohamed Amine Aiche, Elkhansa Yahia, Leila Mallem, Mohamed Salah Boulakoud

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Exposure to endocrine disrupting (ED) during life may cause long-term health effects, the population is exposed to chemicals present in air, water, food and in a variety of consumer and personal care products. Previous research indicates that a wide range of pesticides may act as endocrine disrupters. The azole fungicides propiconazole and propineb have been shown to react through several endocrine disrupting mechanisms, and to induce various endocrine disrupting effects. The purpose of this study was to evaluate the effects of two fungicides; propiconazole and propineb tested separately and in combination, on liver function. The experimental was applied on male Wistar rats dosed orally with Propiconazole 60 mg/kg/day, Propineb 100 mg/kg/day and their mixture 30 mg Propiconazole/kg/day + 50 mg Propineb /kg/day for 4 weeks, for result, a significant increase in liver weights in both treated groups with propineb, propiconazole and their mixture by reference with controls group. Also, highly significant mean values of markers of liver function such as transaminases (ALT/AST) and the activity of alkaline phosphatase (ALP) in all treated groups. The antioxidant activity showed a significant decrease in the hepatic glutathione content (GSH) and glutathione peroxidase (GPX) in all treated groups.

Keywords: endocrine disrupting, pesticide mixture, propineb, propiconazole, liver, oxidative stress

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Authors: Ibrahim I. Elshahawy

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The objective of the present study was to investigate the effect of green tea extract on serum oxidant and antioxidant profile, liver and kidney function. 40 Friesian calves are included in this study and allocated into two groups: Group I (n=20) clinically healthy calves showing no clinical abnormalities, not receiving any treatment and served as control; group II (n=20) received green tea extract (GTE) for 30 days. Non-significant changes in blood urea nitrogen (BUN) were detected between groups, on contrary, serum creatinine and activities of liver enzymes aspartate transaminase (AST) and alanine transaminase (ALT) were significantly different between two groups. There were significant increases in the mean values of serum antioxidative parameters (total antioxidant capacity, catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase) in group II. Whereas, the activity of lipid peroxidase significantly decreased in GTE treated calves when compared to control.

Keywords: green tea extract, antioxidants, oxidants, calves

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Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit

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Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.

Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase

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Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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Authors: Dina Atmani-Kilani, Farah Yous, Djebbar Atmani

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The etiology of peptic ulcer is closely related to stress, excessive consumption of nonsteroidal anti-inflammatory drugs, or ethanol. Clematis flammula (Ranunculaceae) is a medicinal plant widely used by rural populations to treat inflammatory disorders. This study was designed to assess the gastroprotective potential of C. flammula extracts. Gastric ulcer was induced by stress, indomethacin, HCl / ethanol, and absolute ethanol on NMRI-type mice. The antioxidant potency of the ethanolic extract of Clematis flammula (EECF) was evaluated on catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities. Glutathione (GSH) and malonaldehyde (MDA) levels were also quantified. The anti-inflammatory potential was evaluated through the effect of EECF on myeloperoxidase activity (MPO) and vascular permeability. Complementary tests concerning the quantification of mucus levels, gastric motility, inhibition of ATPase H+/K+activity, as well as a histopathological study were also undertaken to explore the mechanism of action of the EECF. The EECF exhibited a significant (p <0.001) and optimal (100 mg/kg) gastroprotective effect by elevating SOD, CAT, and GSH levels, thereby minimizing the production of MDA and lowering the activity of MPO and vascular permeability. EECF also increased the rate of mucus production, decreased gastric motility, and completely suppressed the H+/K+ ATPase activity. Histopathological study confirmed the effectiveness of the extract in the prevention of peptic ulcer. The results obtained in this study demonstrated the gastro-protective effect of EECF via acidic antioxidant, anti-inflammatory, cytoprotective and anti-secretory mechanisms, which may justify its use as a substitute in peptic ulcer treatment.

Keywords: clematis flammula, superoxide dismutase, myeloperoxidase, ATPase, pump

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF, and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Matthew Ocheleka Itodo, Ogo Agbo Ogo, Agnes Ogbene Abutu, Bawa Inalegwu

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Hyperlipidemia is characterised by elevated serum total cholesterol and low density and very low-density lipoprotein cholesterol and decreased high-density lipoprotein are the risk factor for coronary heart diseases. There are claims by traditional medicine practitioners in Nigeria that Moringa oleifera plants are used for the treatment of cardiovascular diseases, but it appears there is no scientific research and, publication or documented work to verify these claims. This study aimed to determine the effect of methanol root extracts of Moringa oleifera on Lipid profile, Atherogenic indices and 3 hydroxyl 3 methylglutaryl Coenzyme A reductase activity of poloxamer 407-induced hyperlipidemic rats. The animals were grouped into 8; Group 1: Normal control, Group 2: Hyperlipidemic control. Groups 2 to 8 were induced with Poloxamer 407 1000 mg/Kg body weight. However, group 3 were treated with standard drugs (atorvastatin). Group 4 was treated with crude extract, and groups 5 to 8 were treated with purified fractions from column chromatography. The preliminary antihyperlipidemic study showed Methanol root extract at 200 mg/kg body weight significantly (p≤0.05) decreased total cholesterol, low-density lipoprotein, triacylglyceride, 3 hydroxyls 3 methylglutaryl Coenzyme A reductase, and increase high-density lipoprotein of hyperlipidemic treated groups. Screening the extracts for the most potent anti-hyperlipidemic activity reveals that fraction 1 of Total Cholesterol and Fraction 3 of Triacylglyceride have the highest percentage reduction of 56% and 51%, respectively. The atherogenic risk factor of all induced treated rats shows a significant (p<0.05) decrease in levels of Castelli’s risk index II, atherogenic index of plasma and a significant (p<0.05) higher level of Castelli’s risk index I ratio. The study shows that the methanol extract of root possesses antihyperlipidemic effects and may explain why it has been found to be useful in the management of cardiovascular diseases by traditional medicine practitioners.

Keywords: hyperlipidemia, moringa oleifera, poloxamer 407, lipid profile

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Authors: A. Babaei Zarch, S. Kianbakht, H. Fallah Huseini, P. Changaei, A. Mirjalili, J. Salehi

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Background: Malva Sylvestris L. has antioxidant property and is widely used in the traditional medicine to treat gastrointestinal, respiratory, skin and urological disorders. Objective: In this study the protective effect of Malva Sylvestris against sodium fluoride-induced nephrotoxicity in rat were evaluated. Methods: The Malva Sylvestris flower extract was prepared and injected intraperitoneally at the doses of 100, 200, 400 mg/kg/day to group of rats ( 10 in each group) for 1 week and subsequently 600 ppm sodium fluoride was added to the rats drinking water for 1 additional week. After these steps, the rats’ serum levels of urea, creatinine, reduced glutathione, catalase and malondialdehyde were determined. The histopathologies of the rats’ kidneys were also studied. Results: Sodium fluoride administration increased levels of BUN, creatinine glutathione, catalase activity and decreased malondialdehyde indicating induction of nephrotoxicity in rats. Malva Sylvestris extract pretreatment significantly decreased the BUN and creatinine levels (P<0.05). Moreover, the levels of catalase and glutathione were increased by Malva, and this increase were also statistically significant (P<0.05). All three doses of Malva extract decreased the malondialdehyde level, but it was significant only for the doses of 200 and 400 mg/kg/day (P<0.05). Histopathological findings also showed protective effect of Malva against renal damage induced by sodium fluoride. Conclusion: The results suggest that Malva Sylvestris has protective effect against sodium fluoride-induced nephrotoxicity maybe mediated by its antioxidant property.

Keywords: malva sylvestris, nephrotoxicity, sodium fluoride, rat

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Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty

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Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.

Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat

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Authors: B. Dejanova, S. Petrovska, L. Todorovska, J. Pluncevic, S. Mancevska, V. Antevska, E. Sivevska, I. Karagjozova

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Introduction: Aging process is mainly related to endothelial function which may be impaired by oxidative stress (OS). Exercise is known to be beneficial to aging process, which may improve health and prevent appearance of chronic diseases in elderly. The aim of the study was to investigate the OS markers related to exercise. Methods: A number of 80 subjects (healthy volunteers) were examined (38 male and 32 female), divided in 3 age groups: group I ≤ 30 years (n=24); group II – 31-50 years (n=24); group III - ≥ 51 year (n=32). Each group was divided to subgroups of sedentary subjects (SS) and subjects who exercise (SE). Group I: SS (n=11), SE (n=13); group II: SS (n=13), SE (n=10); group III: SS (n=23) SE (n=9). Lipid peroxidation (LP) as a fluorimetric method with thiobarbituric acid was used to estimate OS. Antioxidative status was determined by cell antioxidants such as enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPx) and glucose 6 phosphate (G-6-PD); and by extra cell antioxidants such as glutathione reductase (GR), nitric oxide (NO) and total antioxidant capacity (TAC). Results: Increased values of LP were noticed along the aging process: group I – 3.30±0.3 µmol/L; group II – 3.91±0.2 µmol/L; group III – 3.94±0.8 µmol/L (p<0.05), while no statistical significance was found between male and female subjects. Statistical significance for OS was not found between SS and SE in group I as it was found in group II (p<0.05) and in group III (p<0.01). No statistical significance was found for all cell antioxidants and GR within the groups, while NO and TAC showed lower values in SS compared to SE in II (p<0.05) and in group III (p<0.05). Discussion and conclusion: Aging process showed increased OS which may be either due to impaired function of scavengers of free radicals or due to their enormous production. Well balanced exercise might be one of the factors that keep the integrity of blood vessel endothelium which slows down the aging process. Possible mechanism of exercise beneficial influence is shear stress by upregulation of genes coding for nitric oxide bioavailability. Thus, due to obtained results we may conclude that OS is found to be diminished in the subject groups who perform exercise.

Keywords: oxidative stress, aging process, exercise, endothelial function

Procedia PDF Downloads 365

Authors: D. M. El-Tanbouly, R. M. Abdelsalam, A. S. Attia, M. T. Abdel-Aziz

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Lipopolysaccharide (LPS) endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis. LPS administration induces systemic inflammation that mimics many of the initial clinical features of sepsis and has deleterious effects on several organs including the liver and eventually leading to septic shock and death. The present study aimed to investigate the protective effect of magnesium, a well-known cofactor in many enzymatic reactions and a critical component of the antioxidant system, on hepatic damage associated with LPS induced- endotoxima in mice. Mg (20 and 40 mg/kg, po) was administered for 7 consecutive days. Systemic inflammation was induced one hour after the last dose of Mg by a single dose of LPS (2 mg/kg, ip) and three hours thereafter plasma was separated, animals were sacrificed and their livers were isolated. LPS-treated mice suffered from hepatic dysfunction revealed by histological observation, elevation in plasma transaminases activities, C-reactive protein content and caspase-3, a critical marker of apoptosis. Liver inflammation was evident by elevation in liver cytokines contents (TNF-α and IL-10) and myeloperoxidase (MPO) activity. Additionally, oxidative stress was manifested by increased liver lipoperoxidation, glutathione depletion, elevated total nitrate/nitrite (NOx) content and glutathione peroxidase (GPx) activity. Pretreatment with Mg largely mitigated these alternations through its anti-inflammatory and antioxidant potentials. Mg, therefore, could be regarded as an effective strategy for prevention of liver damage associated with septicemia.

Keywords: LPS, liver damage, magnesium, septicemia

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Authors: Rim Frikha, Maha Ben Jema, Moez Elloumi, Tarek Rebai

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Background: Acute lymphoblastic leukemia (ALL); a common blood cancer characterized by the interaction between genetic and environmental factors. Methylenetetrahydrofolate reductase (MTHFR) is an essential folate metabolic enzyme in the processes of DNA synthesis and methylation. A common functional variant of the MTHFR gene, the A1298C, which induces disturbances in folate metabolism, may affect susceptibility to ALL. Objective: The present study aimed to assess the prevalence of MTHFR polymorphism A1298 > C in Tunisian children with ALL. Materials and Methods: A total of 28 Tunisian ALL children were enrolled in this study. Genomic DNA was extracted from whole venous blood collected in ethylenediaminetetraacetic acid (EDTA). Genotyping was carried out with restriction fragment length polymorphism (RFLP) using MboII restriction enzyme. Genotype distribution and allele frequency of MTHFR A1298C was calculated in ALL patients. Results: The A1298C variant of MTHFR was found in 11(19.6%) heterozygous and one homozygous patient (3.5%). Conclusions: This result highlights that A1298C polymorphism of MTHFR is common in Tunisian childhood ALL and suggests that this variant may have a potential role in leukemogenesis. Genotyping of large samples and different ethnicities are required to validate these findings.

Keywords: methylenetetrahydrofolate reductase, acute lymphoblastic leukemia, A1298C variant, prevalence

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Chouahda Salima, Soltani Noureddine

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The present study is a part of biological control against mosquitoes. It aims to assess the impact of two xenobiotics (a selective insect growth regulator: halofenozide and heavy metals: cadmium, more toxic and widespread in the region) in mosquitofish: Gambusia affinis. Several approaches were examined: Acute toxicity of cadmium and halofenozide: The acute toxicity of cadmium and halofenozide was examined in juvenile and adult males and females of G. affinis at different concentrations, cadmium causes mortality of the species studied with a relation dose-response. In laboratory conditions, the impact of cadmium was determined on two biomarkers of environmental stress: glutathione and acetylcholinesterase. The results show that the juvenile followed by adult males are more susceptible than adult females, while the halofenozide does not have any effect on the mortality of juvenile and adult males and females of G.affinis. Chronic toxicity of cadmium and halofenozide: both xenobiotics were added to the water fish raising at different doses tested in juveniles and adults males and females during two months of experience. Growth and metric indices; results show that halofenozide added to the water juveniles of G. affinis has no effect on their growth (length and weight). On the other side, the cadmium at the dose 5 µg/L shows a higher toxicity against juvenile, where he appears to reduce significantly their linear growth and weight. In females, the both xenobiotics have significant effects on metric indices, but these effects are more important on the hepatosomatic index that the gonadosomatic index and the coefficient of condition. Biomarkers; acetylcholinesterase (AChE), glutathione S-transferase (GST) and glutathione (GSH) used in assessing of environmental stress were measured in juveniles and adults males and females. The response of these biomarkers reveals an inhibition of AChE specific activity, an induction of GST activity, and decrease of GSH rates in juveniles in the end of experiment and during chronic treatment adult males and females. The effect of these biomarkers is more pronounced in females compared to males and juveniles. These different biomarkers have a similar profile for the duration of exposure.

Keywords: gambusia affinis, insecticide, heavy metal, morphology, biomarkers, chronic toxicity, acute toxicity, pollution

Procedia PDF Downloads 288

Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

Procedia PDF Downloads 331

Authors: Faheema Khan

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We have investigated the effects of salt stress on the stability of plant growth, water relations, photosynthetic variables, lipid peroxidation and antioxidant system in salt-tolerant (PK-327) and salt-sensitive (PK-471) soybean genotypes. Ten-day-old salt-tolerant and salt-sensitive soybean plants were subjected to 0-150 mM NaCl for 15 days. While the growth of genotype PK-327 was not affected significantly up to 75 mM NaCl treatment, the growth of the PK-471 was reduced significantly beyond 25 mM NaCl treatments. Salt stress caused severe impairments in photosynthetic variables like photosynthetic rate, chlorophyll fluorescence and chlorophyll content, being more pronounced in salt-sensitive genotype than in salt-tolerant.The activities of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) were higher in PK-327 than in PK-471 at various levels of salt treatments.It is concluded that tolerance capacity of PK-327 against salinity can be associated with the ability of this genotype in keeping an active photosynthetic system and strong antioxidant defence system.

Keywords: salt stress, soybean, antioxidant, photosynthesis

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Authors: Richa Mardianingrum, Srie R. N. Endah

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In this research, we have designed four isoniazid derivatives i.e., isonicotinohydrazide (1-isonicotinoyl semicarbazide, 1-thiosemi isonicotinoyl carbazide, N '-(1,3-dimethyl-1 h-pyrazole-5-carbonyl) isonicotino hydrazide, and N '-(1,2,3- 4-thiadiazole-carbonyl) isonicotinohydrazide. The docking and molecular dynamic have performed to them in order to study its interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Based on this research, all of the compounds were predicted to have a stable interaction with Mycobacterium tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA) receptor, so they could be used as an anti-tuberculosis drug candidate.

Keywords: anti-tuberculosis, docking, Inhibin alpha subunit, InhA, inhibition, synthesis, isonicotinohydrazide

Procedia PDF Downloads 155

Authors: Hanen Bouaziz, Françoise Croute, Najiba Zeghal

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In order to investigate the toxic effects of fluoride on cerebrum maturity of suckling mice, we treated adult female mice of Swiss Albinos strain by 500 ppm NaF in their drinking water from the 15th day of pregnancy until the day 14 after delivery. All mice were sacrificed on day 14 after parturition. During treatment, levels of thiobarbituric acid reactive substances, the marker of lipid peroxidation extend, increased, while the activities of the antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and catalase and the level of glutathione decreased significantly in cerebellum compared with those of the control group. These results suggested that fluoride enhanced oxidative stress, thereby disturbing the antioxidant defense of nursing pups. In addition, acetylcholinesterase activity in cerebellum was inhibited after treatment with fluoride. In cerebellum of mice, migration of neurons from the external granular layer to the internal granular layer occurred postnatally. Key guidance signals to these migrating neurons were provided by laminin, an extracellular matrix protein fixed to the surface of astrocytes. In the present study, we examined the expression and distribution of laminin in cerebellum of 14-day-old mice. Immunoreactive laminin was disappeared by postnatal day 14 in cerebellum parenchyma of control pups and was restricted to vasculature despite the continued presence of granular cells in the external granular layer. In contrast, in cerebellum of NaF treated pups, laminin was deposited in organised punctuate clusters in the molecular layer. These data indicated that the disruption of laminin distribution might play a major role in the profound derangement of neuronal migration observed in cerebellum of NaF treated pups.

Keywords: acetylcholinesterase activity, cerebellum, laminin, oxidative stress, suckling mice

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