Effect of glutamine on cisplatin-induced nephrotoxicity and antitumor efficacy in mice

Nephrotoxicity is a dose-limiting factor in clinical use of cisplatin.This study aimed at investigating the protective role of two g1utamine[31n] doses against cisplaun-imlucecI nephrotoxictty in normal mice, and investigating their effect on the antitumor efficacy of ciplatin in mice bearing Ehrlich ascites carcinoma[EAC]. Experiment 1: 60 female albino mice were divided into 6 groups, 10 mice each. The first group received a single i.p. injection with normal saline and served as control. The second group received a single i.p.5 mg/kg body weigt cisplatin injection. The third and fourth groups received oral doses of glutamine 150 and 300mg/kg body weight respectively. The fifth and sixth groups received oral glutamine doses as the third and fourth groups one hour prior to Cs injection respectively. Animals were sacrified 7days after cisplatin injection, sera were collected and kidney were surgically removed and 10% homogenates were prepared for detection of creatinine level, malondialdehyde[MDA], reduced glutathione level[GSH], and glutathione peroxidase[GSH-Px].Experiment II for investigating antitumor efficacy, 60 mice bearing i.p. EAC, were treated as mentioned in experiment I The mean survival time was determined. Experiment III, the effect of such treatments on tumor growth delay was also assessed in 60 mice bearing s.c. EAC. Cisplatin injection alone induced a significant increase in serum creatinine, renal MDA, decrease of GSH levels and GSH-Px activity. Histological examination confirmed renal damage. Pretreatment with glutamine significantly attenuated the disturbance induced by cisplatin in creatinine, MDA, GSH levels, GSH-Px activity in a dose dependent manner. Glutamine in low and high dose reserved the improvement of the mean survival time induced by cisplatin. Moreover, pretreatment with glutamine high dose significantly improved the effect of cisplatin on tumor growth delay. These data suggest that glutamine may decrease the toxicity and oxidative stress of cisplatin, besides improving its antitumor efficacy

Hepatitis c virus and hepatocellular carcinoma

Different etiological factors such as hepatitis viral infection, alcohol, aflatoxin and chemical carcinogens were mentioned in relation to HCC. However, the global distribution of HCC is strongly linked to the prevalence of hepatitis virus infection. The exact pathogenic mechanisms involved in viral-associated HCC are unclear although direct and indirect mechanisms are possible. Direct carcinogenicity is less certain in HCV-Induced HCC since it is a typical RNA virus and therefore the integration of viral genome into host cell chromosomes has not been shown to occur. However, the presence of two conserved potential nuclear localization signals and a DNA binding motif in the HCV core protein suggest a possible functional role as a regulatory element. Moreover, some studies demonstrated that this protein interacts with certain cellular proto-oncogenes at the transcriptional level, resulting in the promotion of cell proliferation and thus affecting normal hepatocyte growth. Therefore the pathogenesis of HCC may be attributed at least in part to the upregulation of hepatocyte growth induced by HCV core protein and other viral proteins like NS3 and NS5. However, the process of malignant transformation represents a dynamic interplay between classes of genes; oncogenes, tumor suppressor genes, mismatch repair genes, genes controlling apoptosis and cell cycle regulatory genes. In conclusion, since the exact mechanism of action of HCV in the context of HCC is still poorly understood, clarification of the molecular basis of viral replication in hepatocytes, the possible genetic and cytogenetic abnormalities that may be induced by the virus were emphasized in this review. Moreover, early detection of hepatocellular changes by molecular biomarkers may help to detect individuals at high risk of development HCC, thus allowing more effective intervention for cure or prevention

Effects of jurak smoke condensate on enzyme activity of the mouse

The effect of jurak smoke condensate on the activities of alkaline phosphatase, glucose 6-phosphatase, 5-nucleotidase, and cholinesterase of mouse liver and small intestine was investigated. Jurak smoke condensate was administered orally by stomach tube five times weekly over a three-month period. Fifteen animals were used at 1,2, and 3 months after the start of the administration, with 5 animals killed on days 1,5 and 9, and the liver and small intestine removed for enzyme assays. The activities of all four enzymes, which are known to be sensitive to toxic agents, were significantly affected. These results indicate that the low content of tobacco leaves in jurak paste and the filtration of the smoke by water in the sheesha reservoir are not sufficient to make the smoke inhaled by smokers risk free

Pathobiochemical studies on the effect of cytoxan, 5- fluorouracil and methotrexate [CMF] on the liver of mice

The effect of Cyclophosphamide, Methotrexate and Fluorouracil [CMF] on the liver enzymes and liver histopathology was investigated in experimental mice. The drugs were administered on single drug bases and in combination in two schedules, one-day pulse and/or once every other day for 5 doses. The toxicity was measured by determination of serum liver enzymes [5-Nucleotidase, Alkaline phosphatase and glucose-6-phosphatase]. Histopathological examination of mice liver showed that the initial changes that were observed by one day pulse administration was stronger than that observed after repeated small doses. However, the rate of recovery was much rapid after single administration. Among the enzymes tested it seems that serum alkaline phosphatase was the most sensetive one that reflects the pathological changes of the liver