Effects of Exercise and Zinc Supplementation on Cytokine Release in Young Wrestlers

The present study aims to examine the effect of zinc supplementation on the release of some cytokines in young wrestlers actively involved in wrestling. A total of 40 male subjects of the same age group were included in the study: half were wrestlers and the other half were not involved in sports. The subjects were equally divided into four groups and treated during an 8-week period as follows: group 1, zinc-supplemented athletes; group 2, non-supplemented athletes; group 3, zinc-supplemented sedentary subjects, and group 4, non-supplemented sedentary group. Blood samples were taken from each subject at the beginning and at the end of the study period. The serum tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interpheron-γ levels (IFN-γ) were determined using the enzyme-linked immunosorbent assay method. At the beginning of the study, there were no significant differences of the measured parameters between the four study groups. At the end of the study, the levels of TNF-α, IL-2, and IFN-γ were significantly higher in the two zinc-supplemented groups compared to those that did not receive supplementation, regardless of the activity status (p < 0.01).     

Alleviation of dimethylnitrosamine-induced liver injury and fibrosis by betaine supplementation in rats

Previous studies suggested that betaine intake might antagonize the induction of oxidative stress-mediated acute liver injury through regulation of the sulfur-amino acid metabolism. In this study we examined the protective effects of betaine on chronic liver injury and fibrosis induced by dimethylnitrosamine (DMN). Male rats were supplemented with betaine (1%, w/v) in drinking water from 2 weeks prior to the initiation of DMN treatment (10 mg/(kg day), i.p., 3 days/week, for 1, 2, or 4 weeks) until sacrifice. Induction of liver injury was determined by quantifying serum alanine aminotransferase, aspartate aminotransferase activities, bilirubin levels, hepatic xenobiotic-metabolizing capacity, histopathological changes and 4-hydroxyproline levels. Development of oxidative injury was estimated by malondialdehyde (MDA) levels and total oxyradical scavenging capacity (TOSC) of liver and serum toward hydroxyl, peroxyl radicals, and peroxynitrite. Progressive changes in the parameters of liver injury and fibrosis were evident in the rats challenged with DMN. Elevation of MDA levels in liver was significant before the onset of a change in any parameters determined in this study. Betaine supplementation markedly attenuated the induction of hepatotoxicity and fibrosis by DMN. Elevation of MDA and the reduction of TOSC were also depressed significantly. Development of liver injury corresponded well with the induction of oxidative stress in rats treated with DMN, both of which are inhibited effectively by betaine supplementation. It is suggested that betaine may protect liver from fibrogenesis by maintaining the cellular antioxidant capacity.     

Effect of soybean oil on atherogenic metabolic risks associated with estrogen deficiency in ovariectomized rats

The aim of the present study was to investigate the cardiac biomarker changes in experimental bilateral ovariectomized (OVX) rats in addition to evaluating the role of soybean oil-supplemented diet to attenuate these alterations. Female rats were divided into four groups and treated for 2 months as follows: groups 1 and 2 fed with standard diet with or without 15% soybean oil. Groups 3 and 4 were bilateral OVX and received the standard diet with or without 15% soybean oil. The results revealed that rats subjected to ovariectomy exhibited an inhibition in estrogen and high-density lipoprotein cholesterol levels and marked increase of lipid profile, low-density lipoprotein cholesterol, and VLDL-C accompanied with a marked elevation in atherogenic index, cardiac enzyme activity, tumor necrosis factor-α, and C-reactive protein. Signs of cardiovascular injury which included an increase in cardiac thiobarbituric acid-reactive substances were concomitantly noticed with a reduction in the reduced glutathione, total antioxidant capacity, and superoxide dismutase. However, supplementation of soybean oil resulted in the restoration of the changed lipid profile and improved cardiac biomarkers near to normal values as well as improved inflammatory and antioxidant status. It was concluded that consumption of soybean oil may have a role in retarding atherosclerosis and risk of cardiovascular disorders associated with estrogen deficiency in ovariectomy status.     

Zinc prevention and treatment of alcoholic liver disease

Alcoholic liver disease (ALD) is associated with decreases in zinc (Zn) and its major binding protein, metallothionein (MT), in the liver. Studies using animal models have shown that Zn supplementation prevents alcohol-induced liver injury under both acute and chronic alcohol exposure conditions. There are hepatic and extrahepatic actions of Zn in the prevention of alcoholic liver injury. Zn supplementation attenuates ethanol-induced hepatic Zn depletion and suppresses ethanol-elevated cytochrome P450 2E1 (CYP2E1) activity, but increases the activity of alcohol dehydrogenase in the liver; an action that is likely responsible for Zn suppression of alcohol-induced oxidative stress. Zn also enhances glutathione-related antioxidant capacity in the liver. At the cellular level, Zn inhibits alcohol-induced hepatic apoptosis partially through suppression of the Fas/FasL-mediated pathway. Zn supplementation preserves intestinal integrity and prevents endotoxemia, leading to inhibition of endotoxin-induced tumor necrosis factor-alpha (TNF-alpha) production in the liver. Zn also directly inhibits the signaling pathway involved in endotoxin-induced TNF-alpha production. These hepatic and extrahepatic effects of Zn are independent of MT. However, low levels of MT in the liver sensitize the organ to alcohol-induced injury, and elevation of MT enhances the endogenous Zn reservoir and makes Zn available when oxidative stress is imposed. Zn has a high potential to be developed as an effective agent in the prevention and treatment of ALD.     

Identification of protein kinase C inhibitory activity associated with a polypeptide isolated from a phage display system with homology to PCM-1, the pericentriolar material-1 protein

L-arginine may aid in the liver detoxification and may benefit in the treatment of liver disorders such as liver injury. The present study was to investigate the possible protective and curative effects of L-arginine on carbon tetrachloride (CCl(4)) induced hepatotoxicity. Mice received a single dose of CCl(4). L-arginine treatment was given for 6 days prior or post to CCl(4) injection. CCl(4)-intoxication caused marked liver cell necrosis with inflammatory and apoptotic lesions. L-arginine treatment reduced hepatic necrosis and inflammation. CCl(4)-intoxication also enhanced hepatic lipid peroxidation, decreased hepatic GSH level and inhibited the activities of antioxidant enzymes. Pre-treatment and post-treatment with L-arginine decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results suggest that L-arginine administration has hepatoprotective and hepatocurative effects against CCl(4) induced hepatotoxicity in mice.     

Molecular evidences on the benefit of N-acetylcysteine in experimental colitis

Inflammatory bowel disease (IBD) is a chronic recurrent disease of the digestive tract with an unknown etiology. The aim of this study was to examine the possible protective effects of N-acetylcysteine (NAC) in the mouse model of IBD by measuring specific biomarkers in the colon cells. Colitis was induced by administration of dextran sodium sulfate (DSS) in drinking water (3%) for 7 days. Three doses of NAC (106, 160, and 240 mg/kg) were given after induction of colitis (4 days post DSS) for 4 days by gavage. Lipid peroxides (LP), total antioxidant power (TAP), total thiol molecules (TTM), tumor necrosis factor-α (TNF-α), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT) were measured in the colon homogenate of the treated animals. NAC (160 and 240 mg/kg) significantly decreased LP, TNF-α, NO and increased TTM, SOD, and CAT. The TAP was also increased by NAC (240 mg/kg). It is concluded that moderate to high doses of NAC improves cellular biomarkers of IBD in mice. Further studies should be trialled in humans suffering from two common inflammatory bowel disease called ulcerative colitis and Crohn’s disease.     

Induction of heme oxygenase-1 improves cold preservation effect of liver graft

We have examined the protective effect and mechanisms of heme oxygenase-1 (HO-1) induction in rat liver model of ex vivo cold ischemia preservation using cobalt protoporphyrin (CoPP) as HO-1 inducer and zinc protoporphyrin (ZnPP) as HO-1 inhibitor. There was a decrease in both aspartate transaminase and lactate dehydrogenase activities and in malondialdehyde level in liver of the CoPP-treated group compared with controls (p < 0.05). In the CoPP-treated rats, the histological signs of reperfusion injury were much lower than in control. Up-regulation of HO-1 expression was also associated with reduced levels of tumor necrosis factor α and interleukin-6. Markedly fewer apoptotic liver cells (determined by TUNEL assay) could be detected in CoPP-treated group compared with the control group. These protective effects were prevented by administration of ZnPP. In conclusion, induction of HO-1 provides protection against liver injury during cold ischemia preservation and improves the preservation of liver graft. The mechanisms underlying these beneficial effects include reduction of oxidative injury and of inflammatory response and prevention of apoptosis. Published in Russian in Biokhimiya, 2007, Vol. 72, No. 5, pp. 674–681.     

Evaluation of possible mechanisms of protective role of Tamarix gallica against DEN initiated and 2-AAF promoted hepatocarcinogenesis in male Wistar rats

We have previously reported that Tamarix gallica caused a marked inhibition of thioacetamide-induced hepatotoxicity, oxidative damage and early tumor promotion related events in the liver. These results strongly indicates that T. gallica may have chemopreventive potential. Therefore, in the present study, we examined the inhibitory effects of T. gallica methanolic extract on diethylnitrosamine (DEN) initiated and 2-acetyl aminofluorene (2-AAF) promoted liver carcinogenesis in male Wistar rats. Interestingly, it was found that T. gallica (25 and 50 mg/kg body wt.) resulted in a marked reduction of the incidence of liver tumors. The study was further histologically confirmed. Furthermore to understand the underlying mechanisms of chemopreventive action by T. gallica we evaluated the levels activities of hepatic antioxidant defense enzymes, ornithine decarboxylase activity and hepatic DNA synthesis as a marker for tumor promotion since direct correlation between these marker parameters and carcinogenicity have been well documented. Treatment of male Wistar rats for five consecutive days with 2-AAF i.p. induced significant hepatic toxicity, oxidative stress and hyperproliferation. Pretreatment of T. gallica extract (25 and 50 mg/kg body wt.) prevented oxidative stress by restoring the levels of antioxidant enzymes and also prevented toxicity at both the doses. The promotion parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF administration in diet with partial hepatectomy (PH) were also significantly suppressed dose-dependently by T. gallica. Therefore, we can conclude that ultimately the protection against liver carcinogenesis by T. gallica methanolic extract might be mediated by multiple actions, which include restoration of cellular antioxidant enzymes, detoxifying enzymes, ODC activity and DNA synthesis.