Search results for: reporter mice

Authors: Kun Chun, Jin-Chun Heo, Sang-Han Lee

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Asthma is a chronic airway inflammatory disease characterized by the infiltration of inflammatory cells and tissue remodeling. In this study, we examined the anti-asthmatic activity of a derivative of L-allo threonine by in vitro and in vivo anti-asthmatic assays. Ovalbumin (OVA)-induced C57BL/6 mice were used to analyze lung inflammation and cytokine expressions for exhibiting anti-atopic activity of the derivative. LX519290, a derivative of L-allo threonine, induced an increased IFN-γ and a decreased IL-10 mRNA level. This compound exhibited potent anti-asthmatic activity by decreasing immune cell infiltration in the lung, and IL-4 and IL-13 cytokine levels in the serum of OVA-induced mice. These results indicated that chronic airway injury was decreased by LX519290. We also assessed that LX519290 inhibits infiltration of immune cell, mucus release and cytokine expression in an in vivo model. Our results collectively suggest that the L-allo threonine is effective in alleviating asthmatic symptoms by treating inflammatory factors in the lung.

Keywords: asthma, L -allo threonine, LX519290, mice

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Authors: Xingxin Wu, Fenli Shao, Tao Tan, Yang Tan, Yang Sun, Qiang Xu

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Psoriasis is a chronic inflammatory skin disease that affects about 2% of the world's population. IL-23 signaling plays a key role in the pathogenesis of psoriasis. Control of IL-23 release by small molecule compounds during developing psoriasis has not been well established. Here, we show that compound 1, a small molecule nature product, protected mice from imiquimod-induced psoriasis with improved skin lesions, reduced skin thickness, and reduced IL-23 mRNA expression in the skin tissue. FACS results showed compound 1 reduced the number of dendritic cells in the skin. Interestingly, compound 1 was not able to ameliorate IL-23-induced psoriasis-like skin inflammation in mice. Further, compound 1 inhibited MyD88-dependent IL-23 mRNA expression induced by LPS, CpG and imiquimod in BMDC cells, but not MyD88-independent CD80 and CD86 expression induced by LPS. The methods included real-time PCR, western blot, H & E staining, FACS and ELISA et al. In conclusion, compound 1 regulates MyD88-dependent signaling to control IL-23 release in dendritic cells, which improves imiquimod-induced psoriasis.

Keywords: dendritic cells, IL-23, toll-like receptor signaling, psoriasis

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Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

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We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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Authors: Alireza Barari, Ahmad Abdi

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The aim of this study was to determine the effects of the effects of six weeks endurance training and Aloe Vera on cyclooxygenase 2 (COX-2) and VEGF levels in mice with breast cancer. For this purpose, 35 rats were randomly divided into 5 groups: control (healthy), control (cancer), training (cancer), Aloe Vera (cancer) and Aloe Vera + training (cancer). Induction of breast cancer tumors were done in mice by planting method. The training program includes six weeks of swimming training was done in three sessions per week. Training time from 10 minutes on the first day increased to 60 minutes in second week, and by stabilizing this time, the water flow rate was increased from 7 to 15 liters per minute. 300 mg per kg body weight of Aloe Vera extract was injected into the peritoneal. Sampling was done 48 hours after the last exercise session. K-S test to determine the normality of the data and analysis of variance for repeated measures and Tukey test was used to analyze the data. A significant difference in the p<0.05 accepted. The results showed that induction of cancer cells significantly increased levels of COX-2 in aloe group and VEGF in training and Aloe Vera + training groups. The results suggest that swimming exercise and Aloe Vera can reduce levels of COX-2 and VEGF in mice with breast cancer.The results of this study, Induction of cancer cells significantly increased levels of COX-2 and MMP-9 in the control group compared with the cancer control group. The results suggest that Aloe Vera can probably inhibit the cyclooxygenase pathway and thus production of prostaglandin E2 decrease of arachidonic acid.

Keywords: endurance training, aloe vera, COX-2, VEGF

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Authors: Yusha'u Shu'aibu Baraya, Kah Keng Wong, Nik Soriani Yaacob

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Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‘Pecah kaca’ or ‘Jin batu’ which have demonstrated potent anticancer effects in both in vitro and in vivo models. In particular, S. crispus subfraction (SCS) significantly reduced tumor growth in N-methyl-N-Nitrosourea-induced breast cancer rat model. However, there is paucity of information on the effects of SCS in breast cancer metastasis. Thus, in this study, the antimetastatic effects of SCS (100 mg/kg) was investigated following 30 days of treatment in 4T1-induced mammary tumor (n = 5) model. The response to treatment was assessed based on the outcome of the tumour growth, body weight and hematological parameters. The results demonstrated that tumor bearing mice treated with SCS (TM-S) had significant (p<0.05) reduction in the mean tumor number and tumor volume as well as tumor weight compared to the tumor bearing mice (TM), i.e. tumor untreated group. Also, there was no secondary tumor formation or tumor-associated lesions in the major organs of TM-S compared to the TM group. Similarly, comparable body weights were observed among the TM-S, normal (uninduced) mice treated with SCS and normal (untreated/control) mice (NM) groups compared to the TM group (p<0.05). Furthermore, SCS administration does not cause significant changes in the hematological parameters as compared to the NM group, which indicates no sign of anemia and toxicity related effects. In conclusion, SCS significantly inhibited the overall tumor growth and metastasis in 4T1-induced breast cancer mouse model suggesting its promising potentials as therapeutic agent for breast cancer treatment.

Keywords: 4T1-cells, breast cancer, metastasis, Strobilanthes crispus

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Authors: Sahar Essa, Hussain A. Safar, Raj Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications in immunologically immature and immunocompromised hosts. Effective CMV vaccines that help diminish CMV disease in transplant patients and avoid congenital infection are of great importance. Though the exact roles of defense mechanisms are unidentified, viral-specific antibodies and cytokine responses are known to be involved in controlling CMV infections. CMV envelope glycoprotein B (UL55/gB), matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. We immunized mice intraperitoneally with these five CMV-related proteins (commercial) for their ability to induce specific antibody responses (in-house immunoassay) and cytokine production (commercial assay) in a mouse model. We observed a significant CMV-antigen-specific antibody response to pp38 and pp65 (E/C ˃2.0, p˂0.001). Mice immunized with pp38 had significantly higher concentrations of GM-CSF, IFN-α, IL-2 IL-4, IL-5, and IL-17A (p˂0.05). Mice immunized with pp65 showed significantly higher concentrations of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF-α. Th1 to Th2 cytokines ratios revealed a Th1 cytokine bias in mice immunized with pp38, pp65, pp150, and gB. We suggest that stimulation with multiple CMV-related proteins, which include pp38, pp65, and gB antigens, will allow both humoral and cellular immune responses to be efficiently activated, thus serving as appropriate CMV antigens for future vaccines.

Keywords: cytomegalovirus, UL99/pp28, UL80a/pp38, UL83/pp65, UL32/pp150, UL55/gB, CMV-antigen-specific antibody, CMV antigen-specific cytokine responses

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Sangeeta Pilkhwal Sah, C. S. Mathela, Kanwaljit Chopra

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Valeriana wallichii DC, an ayurvedic traditional medicine, popularly named as Indian valerian exist as three chemotypes. GC-MS analysis of V. wallichii essential oil in present study showed maaliol as the major constituent followed by the presence of β-gurjunene, acoradiene, guaiol and α-santalene. The results thus confirmed it to be a maaliol chemotype. Further, the antidepressant-like effect of root essential oil (10, 20 and 40 mg/kg p.o.) was investigated in both acute and chronic treatment study using forced swim test in mice. Single administration of different doses produced an inverted U shaped curve and significantly inhibited the immobility period (39.7% and 58%) at doses 10 and 40 mg/kg respectively. Standard drug imipramine significantly decreased immobility period (59.8%). None of the doses altered locomotor activity except a significant decrease of 44.9% was observed with 40 mg/kg (p < 0.05). Similarly, daily administration of essential oil for 14 days produced a dose dependent effect with significantly reduced immobility period (70.9%) at 40 mg/kg dose only whereas imipramine produced 86% decrease (p < 0.05). The neurotransmitter levels in mouse brain were estimated on day 14 after the behavioral study. Significant increase in the level of norepinephrine (10%) and dopamine (23%) (p < 0.05) was found at 40 mg/kg dose, while no change was observed at 10 and 20 mg/kg doses. The antidepressant-like effect of essential oil (40 mg/kg) was prevented by pretreatment of mice with L-arginine (750 mg/kg i.p.) and sildenafil (5 mg/kg i.p). On the contrary, pretreatment of mice with L-NAME (10 mg/kg i.p.) or methylene blue (10 mg/kg i.p.) potentiated the antidepressant action of essential oil (20 mg/kg). The findings thus demonstrated that nitric oxide pathway is involved in mediating antidepressant like effect of essential oil from this chemotype.

Keywords: Valeriana wallichii DC chemotype, essential oil, forced swim test, nitric oxide modulators, neurotransmitters

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Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

Abstract:

Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: Inflammation is widely distributed in patients with Duchenne muscular dystrophy (DMD), and ultimately leads to progressive deterioration of muscle function with the co-effects of chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzymes, heme oxygenase-1 (HO-1). However, whether Nrf2/HO-1 pathway can attenuate muscle inflammation on DMD remains unknown. The purpose of this study was to determine the anti-inflammatory effects of Sulforaphane (SFN) on DMD. Methods: 4-week-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 4 weeks. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Immune cell infiltration in skeletal muscles was analyzed by H&E staining and immuno-histochemistry. Moreover, the expressions of inflammatory cytokines,pro-inflammatory cytokines and Nrf2/HO-1 pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment increased the expression of muscle phase II enzymes HO-1 in Nrf2 dependent manner. Inflammation in mdx skeletal muscles was reduced by SFN treatment as indicated by decreased immune cell infiltration and lower expressions of the inflammatory cytokines CD45, pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the skeletal muscles of mdx mice. Conclusions: Collectively, these results show that SFN can ameliorate muscle inflammation in mdx mice by Nrf2/HO-1 pathway, which indicates Nrf2/HO-1 pathway may represent a new therapeutic target for DMD.

Keywords: sulforaphane, Nrf2, HO-1, inflammation

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Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Sophio Kalmakhelidze, Eka Shekiladze, Tamar Sanikidze, Mikheil Gogebashvili, Nazi Ivanishvili

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Radiation-induced various degrees of brain injury and cognitive impairment have been described after cranial radiotherapy of brain tumors. High doses of ionizing radiation have a severe impact on the central nervous system, resulting in morphological and behavioral impairments. Structures of the limbic system are especially sensitive to radiation exposure. Hence, compounds or drugs that can reduce radiation-induced impairments can be used as promising antioxidants or radioprotectors. In our study Mice whole-body irradiation with 137Cs was performed at a dose rate of 1,1 Gy/min for a total dose of 5 Gy with a “Gamma-capsule-2”. Irradiated mice were treated with Herniarin (20 mg/kg) for five days before irradiation and the same dose was administrated after one hour of irradiation. The immediate and delayed effects of ionizing radiation, as well as, protective effect of Herniarin was evaluated during early and late post-irradiation periods. The results reveal that ionizing radiation (5 Gy) alters the structure of the hippocampus in adult mice during the late post-irradiation period resulting in the decline of memory formation and learning process. Furthermore, Simple Coumarin-Herniarin reveals a radiosensitizing effect reducing morphological and behavioral alterations.

Keywords: ionizing radiation, cognitive impairments, hippocampus, limbic system, Herniarin

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Authors: Cyoung-Huei Huang, Chiu-Li Yeh, Man-Hui Pai, Sung-Ling Yeh

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This study evaluated the effect of different dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups in this study. Mice were fed for 24 d with an AIN-93G diet either with soybean oil (S), a mixture of soybean oil and low fish oil content (LF) or high fish oil content (HF). The ratio of n-6/n-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups provided 2% DSS in drinking water during day 15-19. All mice drank distilled water from day 20-24 for recovery and sacrificed on day 25. The results showed that colitis resulted in higher Th1, Th2, and Th17 and lower Treg percentages in the blood. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Further, the percentages of Th1, Th2, and Th17 cells in the blood were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with n-6/n-3 PUFA ratio 2:1 had more pronounce effects than ratio 4:1. These results suggest that diets with an n-6/n-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared to the n-6/n-3 PUFA ratio 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

Keywords: inflammatory bowel disease, n-3 polyunsaturated fatty acids, helper T lymphocyte, regulatory T lymphocyte

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Authors: Chanya Inprasit, Yi-Wen Lin

Abstract:

Motion sickness (MS) is an acute disorder that occurs in healthy persons without considering gender, age or ethnicity worldwide. All signs and symptoms of MS are the results of confliction and mismatch among neural signal inputs. It is known that no singular remedy works for everybody, and electroacupuncture (EA) is one of the popular alternative therapies used for MS. Our study utilized a mouse model in order to exclude any psychological factors of MS and EA. Mice lack an emetic reflex. Therefore pica behavior, which is a normal consumption of non-nutritive substances, was found to measure the response of MS in mice. In the laboratory, Kaolin was used as a non-nutrient food substance instead of natural substances lacking nutritional value such as wood, cloth, charcoal, soil or grass. It was hypothesized that EA treatment could reduce the symptoms of MS through the TRPV1 pathways. The results of pica behavior showed a significantly increased intake of kaolin in the MS group throughout the experiment period. Moreover, the Kaolin intake of the EA group decreased to the average baseline of the control group. There was no recorded difference in the food and water intake of each group. The results indicated an increase of the TRPV1, pERK, pJNK and pmTOR protein levels in the thalamus after MS stimulation, and a significant decrease in the EA group compared with that of the control group. These findings suggest that TRPV1 pathways are associated in MS mechanisms and can be reduced by EA.

Keywords: electroacupuncture, motion sickness, Thalamus, TRPV1

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Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

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The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

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Authors: Govindan Sudha, Mathumitha Subramaniam, Alamelu Govindasamy, Sasikala Gunasekaran

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The aim of this study was to investigate the protective effect of Hypsizygus ulmarius polysaccharides (HUP) on reducing oxidative stress, cognitive impairment and neurotoxicity in D-galactose induced aging mice. Mice were subcutaneously injected with D-galactose (150 mg/kg per day) for 6 weeks and were administered HUP simultaneously. Aged mice receiving vitamin E (100 mg/kg) served as positive control. Chronic administration of D-galactose significantly impaired cognitive performance oxidative defence and mitochondrial enzymes activities as compared to control group. The results showed that HUP (200 and 400 mg/kg) treatment significantly improved the learning and memory ability in Morris water maze test. Biochemical examination revealed that HUP significantly increased the decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), mitochondrial enzymes-NADH dehydrogenase, malate dehydrogenase (MDH), isocitrate dehydrogenase (ICDH), Na+K+, Ca2+, Mg2+ATPase activities, elevated the lowered total anti-oxidation capability (TAOC), glutathione (GSH), vitamin C and decreased the raised acetylcholinesterase (AChE) activities, malondialdehyde (MDA), hydroperoxide (HPO), protein carbonyls (PCO), advanced oxidation protein products (AOPP) levels in brain of aging mice induced by D-gal in a dose-dependent manner. In conclusion, present study highlights the potential role of HUP against D-galactose induced cognitive impairment, biochemical and mitochondrial dysfunction in mice. In vitro studies on the effect of HUP on scavenging DPPH, ABTS, DMPD, OH radicals, reducing power, B-carotene bleaching and lipid peroxidation inhibition confirmed the free radical scavenging and antioxidant activity of HUP. The results suggest that HUP possesses anti-aging efficacy and may have potential in treatment of neurodegenerative diseases.

Keywords: aging, antioxidants, mushroom, neurotoxicity

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Authors: Alvin Han, Reema Shafi, Alishba Afaq, Jennifer Gommerman, Valeria Ramaglia, Shannon E. Dunn

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Adolescents engaged in contact-sports can suffer from recurrent brain concussions with no loss of consciousness and no need for hospitalization, yet they face the possibility of long-term neurocognitive problems. Recent studies suggest that head concussive injuries during adolescence can also predispose individuals to multiple sclerosis (MS). The underlying mechanisms of how brain concussions predispose to MS is not understood. Here, we hypothesize that: (1) recurrent brain concussions prime microglial cells, the tissue resident myeloid cells of the brain, setting them up for exacerbated responses when exposed to additional challenges later in life; and (2) brain concussions lead to the sensitization of myelin-specific T cells in the peripheral lymphoid organs. Towards addressing these hypotheses, we implemented a mouse model of closed head injury that uses a weight-drop device. First, we calibrated the model in male 12 week-old mice and established that a weight drop from a 3 cm height induced mild neurological symptoms (mean neurological score of 1.6+0.4 at 1 hour post-injury) from which the mice fully recovered by 72 hours post-trauma. Then, we performed immunohistochemistry on the brain of concussed mice at 72 hours post-trauma. Despite mice having recovered from all neurological symptoms, immunostaining for leukocytes (CD45) and IBA-1 revealed no peripheral immune infiltration, but an increase in the intensity of IBA1+ staining compared to uninjured controls, suggesting that resident microglia had acquired a more active phenotype. This microglia activation was most apparent in the white matter tracts in the brain and in the olfactory bulb. Immunostaining for the microglia-specific homeostatic marker TMEM119, showed a reduction in TMEM119+ area in the brain of concussed mice compared to uninjured controls, confirming a loss of this homeostatic signal by microglia after injury. Future studies will test whether single or repetitive concussive injury can worsen or accelerate autoimmunity in male and female mice. Understanding these mechanisms will guide the development of timed and targeted therapies to prevent MS from getting started in people at risk.

Keywords: concussion, microglia, microglial priming, multiple sclerosis

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Authors: Zahid Hussain, Nayyab Sultan

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This study describes the preparation of zinc oxide nanoparticles and their anti-diabetic effect individually and with the combination of Momordica charantia plant extract. This plant is termed bitter melon, balsam pear, bitter gourd, or karela. Blood glucose levels in mice were monitored in their random state before and after the administration of zinc oxide nanoparticles and plant extract. The powdered form of nanoparticles and the selected plant were used as an oral treatment. Diabetes was induced in mice by using a chemical named as streptozotocin. It is an artificial diabetes-inducing chemical. In the case of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg); the maximum anti-diabetic effect observed was 70% ± 1.6 and 75% ± 1.3, respectively. In the case of the combination of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg), the maximum anti-diabetic effect observed was 86% ± 2.0. The results obtained were more effective as compared to standard drugs Amaryl (3mg/kg), having an effectiveness of 52% ± 2.4, and Glucophage (500mg/kg), having an effectiveness of 29% ± 2.1. Results indicate that zinc oxide nanoparticles and plant extract in combination are more helpful in treating diabetes as compared to their individual treatments. It is considered a natural treatment without any side effects rather than using standard drugs, which shows adverse side effects on health, and most probably detoxifies in liver and kidneys. More experimental work and extensive research procedures are still required in order to make them applicable to pharmaceutical industries.

Keywords: albino mice, amaryl, anti-diabetic effect, blood glucose level, Camellia sinensis, diabetes mellitus, Momordica charantia plant extract, streptozotocin, zinc oxide nanoparticles

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Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

Abstract:

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

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Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

Abstract:

Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

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Authors: Levylee Bautista, Dawn Grace Santos, Aishwarya Veluchamy, Jesusa Santos, Ghafoor, Jr. I Haque, Rodolfo Rafael

Abstract:

The booming interest in using natural compounds as an alternative to conventional medications has paved way to focus the attention on plants that provide rich sources of bioactive phytochemicals. For regulatory purposes, evaluation of the genotoxic effects of such alternatives is therefore empirical as part of the plant’s hazard assessment. Sesbania grandiflora is among the plants used as a traditional remedy in folk medicine and a subject of research for its medicinal benefits. This study aimed to evaluate the genotoxic potential induced by S. grandiflora flower methanol extract (SGFME) in terms of the frequency of micronucleus (MN) in polychromatic erythrocyte (PCE) (MNPCE) and PCE ratio employing the micronucleus assay. The frequency of MN was examined in bone marrow cells (BMCs) obtained from male Swiss albino mice exposed in vivo to four different concentrations (11.25, 22.5, 40, and 90 mg/kg) of SGFME and MMC (70 mg/kg; positive control) and sacrificed 24 hours post-intraperitoneal injection. Results showed a significant (p < 0.01) rate of MNPCEs for 11.25 and 22.5 tested concentrations of SGFME and is comparable with the MMC-treated mice. Although PCE ratio values in all doses of SGFME-treated mice were over 0.20, it is worth noting that 40 and 90 tested concentrations of SGFME-treated mice exhibited the lowest value, i.e., 0.22 and 0.28, respectively. The present study has demonstrated that S. grandiflora possesses genotoxic potential for murine BMCs. Such activity could be ascribed from the bioactive compounds present in S. grandiflora that require further isolation and characterization of the active molecules. Likewise, findings of this study warrant a caution of the use of S. grandiflora insomuch as further investigations do not demonstrate their safety.

Keywords: genotoxicity, micronucleus, phytochemicals, Sesbania grandiflora

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Authors: S. Essa, H. Safar, R. Raghupathy

Abstract:

Human cytomegalovirus (CMV) continues to be a source of severe complications to immunologically immature and immune-compromised hosts. Effective CMV vaccine that diminishes CMV disease in transplant patients and avoids congenital infection remains of high importance as no approved vaccines exist. Though the exact links of defense mechanisms are unidentified, viral-specific antibodies and Th1/Th2 cytokine responses have been involved in controlling viral infections. CMV envelope glycoprotein B (UL55/gB), the matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and the assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. In this study, mice were immunized with five HCMV antigens (UL32/pp150, UL80a/pp38, UL99/pp28, and UL83/pp65), and serum samples were collected and evaluated for eliciting viral-specific antibody responses. Moreover, Splenocytes were collected, stimulated, and assessed for cytokine responses. The results demonstrated a CMV-antigen-specific antibody response to pp38 and pp65 (E/C >2.0). The highest titers were detected with pp38 (average E/C 16.275) followed by pp65 (average E/C 7.72). Compared to control cells, splenocytes from PP38 antigen immunized mice gave a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-5, and IL-17A (P<0.05). Also, splenocytes from pp65 antigen immunized mice resulted in a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF- α. The designation of target CMV peptides by identifying viral-specific antibodies and cytokine responses is vital for understanding the protective immune mechanisms during CMV infection and identifying appropriate viral antigens to develop novel vaccines.

Keywords: hepatitis C virus, peripheral blood mononuclear cells, neutrophils, cytokines

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Authors: Santram Lodhi, Alok Pal Jain, Awesh K. Yadav, Gopal Rai

Abstract:

Rhodiola rosea L. (Crassulaceae) is commonly known as golden root or rose root. It is a perennial herbaceous plant and most investigated species of the genus Rhodiola. Rhodiola rosea contains flavonoids, terpenoids, phenylpropanoid glycosides and phenylethanol derivatives in the roots of the plant. The objective of present study was to investigate the protective effect of hydroalcoholic extract from Rhodiola rosea roots in DSS induced colitis in mice. The ulcerative colitis was induced by DSS (3%, w/v) in mice and estimated weight loss and stool consistency. Various parameters including Colon length, spleen weights and ulcer index were also measured. The histological observations were observed by H&E staining. Effect of hydroalcoholic extract on various antioxidant parameter of rat colon such as tissue myeloperoxidase (MPO), reduced GSH, SOD concentrations and lipid peroxidation were determined. Pro-inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and nitric oxide (NO) were determined by ELISA. In DSS induced group, mice body weight decreased gradually as compared to the control group. Redness and edema were observed in the colons intensely and scores representing inflammation in this group. The extract treated showed with tissue levels of TNF-α, IL-6 and MPO activity were significantly (p<0.05) increased. The mice treated with higher doses of hydroalcoholic extract (300 mg/kg) significantly reduced the activity compared with standard drug sulfasalazine (100 mg/kg. B.wt). Conclusion: Results of this study were suggested that the efficacy of hydroalcoholic extract, especially at the higher dose, was similar to that of standard drug, which concerned its potential application as a natural medicine for the treatment of ulcerative colitis.

Keywords: phenylpropanoid, Rhodiola rosea, sulfasalazin, ulcerative colitis

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Authors: Suparmi, Israhnanto Isradji, Dina Fatmawati, Iwang Yusuf

Abstract:

Kepel (Stelechocarpus burahol) is one of the traditional plants originating from Indonesia that can be used to prevent pregnancy, launched urine and kidney inflammation. Kepel pulp has compounds alkaloid, triterpenoid, tannin, saponin, and flavonoid, when used will give the hormonal and cytotoxic effect. This study was aimed at evaluating ethanol extract of kepel in vivo for anti-implantation activities. In this experimental study with post test only control group design, 20 female mice were randomly divided into 4 groups. It was divided into the control, the 0,65 mg dose, 1,3 mg dose, and 3,6 mg dose of kepel pulp extract group. The extract soluted in DMSO’s solution and was given 1 ml per mice. The extract was given 10 days before copulation until 18 days of pregnancy. Then, the number of implantation, presence of fetus, and embrio resorbtion were recorded and used to calculate the percentage anti-implantation effect. The results were tested by One-way ANOVA. The mean number of implantation in group control, 0,65 mg;1,3 mg; and 2,6 mg were 5,60±1,14; 6,20± 1,64; 7,60±1,51; 8,00± 1,58, respectively. One way Annova test showed that there is no significant difference in the number of implantation between the group (p > 0,05). The administration of kepel pulp ethanol extract had no effect on the percentage anti-implantation effect and the number of and embrio resorbtion.

Keywords: antiimplantation, fetus, Stelechocarpus burahol, flavonoid

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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

Abstract:

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: Fui Ping Lim, Wen Choong Chua, Toan Thang Phan

Abstract:

Aim: This study investigates the roles of Cord Lining Stem Cells (CLSCs) as potential therapeutic agents for diabetic wounds. Method: 20 genetically diabetic db/db mice were randomly assigned to two arms; (i) control group received placebo treatment (sham media or cells delivery material), and (ii) active comparator received CLSCs. Two full-thickness wounds, each sized 10mm X 10mm were created, one on each side of the midline on the back of the mice. Digital pictures were taken on day 1, 3, 7, 10, 14, 17, 21, 24, 28. Wound areas were analyzed with ImageJ TM software and calculated as percentage of the original wound. Time to closure was defined as the day the wound bed was completely epithelized and filled with new tissues. Results: The CLSCs-treated wounds, showed a significant increase in the percentage of wound closure and achieved 100% closure of the wound sooner than the control group by an average of 3.7 days. The mice treated with CLSCs have a shorter wound closure time (mean closure day: 19.8 days) as compared to the control group (mean closure day: 23.5 days). Conclusion: Our preliminary findings inferred that CLSCs treated wound achieved higher percentage of wound closure within a shorter duration of time.

Keywords: cord lining stem cell, diabetic wound, stem cell, wound

Procedia PDF Downloads 283

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

Abstract:

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, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that 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) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in 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 a novel principle to harness the power of uncouplers for the treatment of DN.

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

Procedia PDF Downloads 82

Authors: O. M. Alabi, F. A. Aderemi, M. O. Ayoola

Abstract:

An aspect of biosecurity measures to ensure good welfare for chickens is rodents’ control. Rats and mice are rodents commonly found in poultry houses in most of the African countries. More than 20,000 species of rat have been identified in Africa among which are; Black house rats (Rattus rattus), East African mole rat (Tachyorcytes splendens), Naked mole rat (Heterocephalus glaber), Zambian mole rat (Fukomys mechowii), African grass rat (Arvicanthis niloticus), Nigerian mole rat (Cryptomys foxi), Target rat (Stochomys longicaudatus) and West African Shaggy rat (Dasymis rufulus). Apart from being destructive, rats and mice are voracious in that they compete with chickens for feed and water thereby causing economical losses to the farmer, they are also vectors to many pathogens of poultry diseases such as Salmonellosis, colibacillosis, ascaridiasis, coryza, pasteurellosis and mycoplasmosis. As bad as these rodents are to the poultry farmers, they are good sources of animal protein to local hunters and other farmers in most African countries. Rat is considered a delicacy in Nigeria and many other African countries hence the need to investigate into how the rats species will not go into extinction. Rodents are usually controlled by poultry farmers with the use of rodenticides which can either be anticoagulant or stomach poison, and with the use of baits. However, elimination of rats and mice is being considered as callous act against these species of animal and their natural existence as human food also. This paper therefore suggests that sanitation methods such as feed removal from rats and mice, controlling feed and water spillage, proper disposal of waste eggs, dead birds and garbage, keeping the surroundings of the poultry clean; rodent proofing by making it difficult for rodents to enter the poultry houses are some of the humane ways of controlling rodents in poultry production to avoid improving the welfare of a particular animal at the expense of the other.

Keywords: management, poultry, rodents, welfare

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Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

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