Hepatoprotective effect of allicin on tissue defense system in galactosamine/endotoxin challenged rats

Allicin (diallythiosulfinate) is the main biologically active component of freshly crushed garlic (Alliaceae Allium sativum Linn.) cloves. It is produced by the interaction of the non-protein amino acid alliin with the enzyme alliinase (alliin lyase, EC 4.4.1.4). D-Galactosamine highly sensitizes the host response of the experimental animal to endotoxin (lipopolysaccharide) and causes fulminant hepatitis within 8h after administration. In D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatitis rats, a significant increase of lipid peroxidation and decreased liver antioxidant enzyme levels are observed. Pretreatment with allicin, the active component of freshly crushed garlic cloves, prevented these alterations.     

HIV-related stigma and NGO-isation in India: a historico-empirical analysis

In response to World Bank critiques in 2007, the Indian Ministry of Health and Family Welfare declared that human immunodeficiency virus (HIV)‐related stigma was a barrier to the participation of non‐governmental organisations (NGOs) in the implementation of HIV prevention targeted interventions. Taking a deeper view of HIV‐related stigma as a historically inflected process of devaluation, this article details the history and transformation of NGO involvement in the HIV epidemic from 1986 through economic liberalisation in the 1990s up to the Second National AIDS Control Programme (NACP II 1999–2006). It additionally examines findings from interviews and participant observation of NGO workers (N = 24) from four targeted intervention NGOs in Delhi funded under NACP II. Analysis reveals that a second wave of HIV‐related NGO involvement has mushroomed in the past two decades, affording NGO workers multiple pathways to credibility in the Indian response to the epidemic. Contradictions embedded in the overlap of these pathways produce stigma, reflecting ‘adverse incorporation’ of the NGO workers. Drawing upon noteworthy exceptions to this trend from the first wave of Indian HIV‐related NGOs, the article calls for NGO participation as an explicitly political project of addressing the social inequalities that shape stigma as well as vulnerability to illness writ large.     

Physiological and antioxidant responses of Salvinia natans exposed to chromium-rich wastewater

Salvinia natans possess capacity to accumulate high concentrations of chromium (Cr). Studies were carried out to evaluate physiological efficiency and defensive potential of plant exposed to Cr-rich wastewater. Among photochemical reactions, photosystem I (PS I) and photosystem II (PS II) activity noted an increase in plants exposed to Cr-rich wastewater. Fluorescence ratio F_v/F_m depicted no alteration in plants exposed to Cr. The activity of ribulose-1,5-biphosphate carboxylase–oxygenase (Rubisco) noted a decline, while transthylakoidal pH gradient (ΔpH) (correlative of photophosphorylation) showed increase in plants exposed to Cr-rich wastewater. Plants lacked the ability to produce malondialdehyde, but possessed efficient enzymic and non-enzymic antioxidant defense mechanisms that played important role in curtailing oxidative stress. The activities of antioxidant enzymes showed alleviation in plants exposed to Cr-rich wastewater. The levels of cellular antioxidants noted decline suggesting a defensive role in protection against oxidative stress caused by Cr. The present findings suggest that Salvinia possess efficient antioxidant machinery that curtails oxidative stress caused by Cr-rich wastewater and protects photosynthetic machinery from damage.     

Meta-analysis of patients with hepatitis C virus genotype 6: 48 weeks with pegylated interferon and ribavirin is superior to 24 weeks

Background

Hepatitis C virus genotype 6 (HCV-6) is common in patients from Southeast Asia and the surrounding regions. Optimal treatment duration for HCV-6 is unknown given the inconclusive evidence from studies with varying methodologies and small sample sizes.

Methods

A literature search for ‘genotype 6’ in MEDLINE and EMBASE in October 2013 produced 161 and 251 articles, respectively. Additional abstracts were identified from four major international GI/liver conferences in 2012/2013. Inclusion criteria were original studies with ≥10 HCV-6 treatment-naïve patients treated with pegylated interferon + ribavirin (PEG IFN+RBV). Exclusion criteria were coinfections with HBV, HIV, other HCV genotypes, and/or other liver diseases. Primary outcome was pooled sustained virologic response (SVR). Heterogeneity was defined by Cochrane Q test (p value of 0.10) and I ² statistic (≥50 %).

Results

A total of 13 studies with 641 patients were included. The pooled SVR estimate was 77 % (CI 70–83 %) (Q value = 38.4, p value <0.001, I ² = 68.7 %) overall, 79 % (CI 73–84 %) for the 48-week group and 59 % (CI 46–70 %) for 24-week group, respectively. In studies with direct comparison of the two groups, SVR was superior in patients treated for 48 versus 24 weeks, OR 1.9 (CI 1.08–3.2, p = 0.026). In studies with direct comparison of patients with rapid virologic response (RVR), there was no difference in SVR between 48 versus 24 weeks, OR 1.74 (CI 0.65–4.64, p = 0.27).

Conclusion

Hepatitis C virus genotype 6 patients should be treated for 48 weeks, and those who achieve RVR may receive the shorter 24-week treatment duration. The high SVR (~80 %) with 48 weeks of PEG IFN+RBV therapy may be a cost-effective option for HCV-6 patients from resource-poor regions.     

Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer

The modulatory efficacy of capsaicin on lung mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, key citric acid cycle enzymes and respiratory chain enzymes during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice was studied. Elevations in mitochondrial LPO along with decrements in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and vitamin A), citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (alpha-KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and respiratory chain enzymes (NADH dehydrogenase and Cytochrome c oxidase) were observed in B(a)P (50mg/kg body weight) administered animals. CAP (10mg/kg body weight) pretreatment decreased lung mitochondrial LPO and augmented the activities of enzymic, non-enzymic antioxidants, citric acid cycle enzymes and respiratory chain enzymes to near normalcy revealing its chemoprotective function during B(a)P induced lung cancer.     

Synergistic effect of nicorandil and amlodipine on lysosomal hydrolases during experimental myocardial infarction in rats.

The synergistic effect of nicorandil (K(ATP) channel opener) and amlodipine (calcium channel blocker) on lysosomal hydrolases in serum and heart was examined by determining the activity of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-D and acid phosphatase on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for 2 d showed significant increase in serum and heart lysosomal hydrolases activity. Isoproterenol administration to rats resulted in decreased stability of the membranes, which was reflected by the lowered activity of cathepsin-D and beta-glucuronidase in mitochondrial, nuclear, lysosomal and microsomal fractions. Pretreatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 d significantly prevented these alterations and restored the enzyme activity to near normal. These findings demonstrate that the pretreatment with nicorandil and amlodipine could preserve lysosomal integrity and hence establish the cardioprotective effect of the combination.     

Anti-peroxidative and anti-hyperlipidemic nature of Ulva lactuca crude polysaccharide on d-Galactosamine induced hepatitis in rats

To find whether pretreatment of Ulva lactuca polysaccharide (ULP) extract could be effective against d-Galactosamine (500 mg/kg body weight, i.p.) induced anomaly in rat. Serum total cholesterol (TC), triglycerides (TG), free fatty acid (FFA), phospholipids (PL), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), tissue lipoperoxides (LPO), hepatic protein thiols, non-enzymatic anti-oxidants glutathione (GSH) and vitamins (E and C) were examined using spectrophotometer. The ultra structural changes of liver during d-Galactosamine and protection offered by ULP were examined by electron microscopy. Seaweed histology and chemical composition of polysaccharides in seaweed were examined. Alcian blue staining showed the presence of sulphated polysaccharide with total sugar (65.4%), sulphate (17.4%), and uronic acid (17.2%) content. d-Galactosamine intoxicated rats showed significant (p < 0.01) liver damage with acute aberration in serum lipid profile, hepatic protein thiols and tissue non-enzymatic anti-oxidants. Assorted deposits of lipid droplets and abnormal appearance of mitochondria was observed in electron microscopy study. Rats pretreated with ULP (30 mg/kg body weight/day/for 21 days) showed a significant inhibition (p < 0.05) against abnormality induced by d-Galactosamine. U.lactuca exhibit anti-peroxidative and anti-hyperlipidemic property.     

Correlation of ‘in vitro’ release and ‘in vivo’ absorption characteristics of rifampicin from ethylcellulose coated nonpareil beads

The purpose of this study was to investigate the possibility to develop different levels of correlation between in vitro dissolution parameters and in vivo pharmacokinetic parameters for three rifampicin formulations. A level A correlation of in vitro release and in vivo absorption could be obtained for individual plasma level data by means of the Wagner and Nelson method. Linear correlation could be obtained when percent dose released in vitro was plotted vs percent dose absorbed in vivo with correlation coefficients between 0.954, 0.983 and 0.997 for the formulations studied. A second level correlation between mean in vitro dissolution time (MDT) and mean in vivo residence time (MRT) was performed with a correlation coefficient of 0.536, 0.420 and 0.335. Finally, it was also possible to establish a good in vitro–in vivo correlation when the T_50%hrs (time taken to release 50% of rifampicin) in vitro and C_max, T_max or AUC in vivo were compared.     

Inhibitory effects of histone deacetylase inhibitor depsipeptide on benzo(a)pyrene- and cyclophosphamide-induced genotoxicity in Swiss albino mice

Depsipeptide (FK228 or FR901228) was evaluated in the mouse bone marrow micronucleus test for its possible protective effect against chromosomal damage induced by benzo(a)pyrene and cyclophosphamide. Three doses of depsipeptide (0.5, 1, and 1.5 mg/kg body weight) were given intravenously to mice for 7 consecutive days prior to administration of genotoxins under investigation. All the three doses of depsipeptide were effective in exerting a protective effect against both benzo(a)pyrene and cyclophosphamide. A significant suppression (34.9% to 67.5%) in the micronuclei formation induced by benzo(a)pyrene and (25.7% to 71.5%) cyclophosphamide was observed following intravenous administration of depsipeptide at doses of 0.5, 1, and 1.5 mg/kg in Swiss albino mice.     

Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice

Summary  Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on lung cancer. Hesperidin is one such naturally occurring flavonoid widely found in citrus fruits. The aim of the present study is to divulge the chemopreventive nature of hesperidin during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice. Administration of B(a)P (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lung specific tumor marker carcinoembryonic antigen (CEA) and serum marker enzymes aryl hydrocarbon hydroxylase (AHH), gamma glutamyl transpeptidase (GGT), 5′nucleotidase (5′ND) and lactate dehydrogenase (LDH) with concomitant decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C. Hesperidin supplementation (25 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in lung cancer. Further the antiproliferative effect of hesperidin was confirmed by histopathological analysis and proliferating cell nuclear antigen (PCNA) immunostaining. Overall, these findings substantiate the chemopreventive potential of hesperidin against chemically induced lung cancer in mice.