Lack of Guanylate Cyclase C results in increased mortality in mice following liver injury

<p>Abstract</p> <p>Background</p> <p>Guanylate Cyclase C (GC-C) expression in the intestine plays a role in the regulation of fluid and ion transport, as well as epithelial cell apoptosis and proliferation. In the adult rat liver, GC-C expression is increased in response to injury. We hypothesized that GC-C is required for repair/recovery from liver injury.</p> <p>Methods</p> <p>We subjected wild type (WT) and GC-C deficient mice to acute liver injury with a single injection of the hepatotoxin carbon tetrachloride. Changes in the level of expression of GC-C and its ligands uroguanylin and guanylin were quantified by real-time PCR. Liver morphology, and hepatocyte necrosis, apoptosis and proliferation, were examined at 1-3 days post-injury in mice on a mixed genetic background. Survival was followed for 14 days after carbon tetrachloride injection in wild type and GC-C deficient mice on both a mixed genetic background and on an inbred C57BL6/J background.</p> <p>Results</p> <p>GC-C deficient mice on the mixed genetic background nearly all died (median survival of 5 days) following carbon tetrachloride injection while WT littermates experienced only 35% mortality. Elevated levels of TUNEL-positive hepatocyte death on post-injury day 1, increased apoptosis on day 2, and increased areas of centrilobular necrosis on days 2 and 3, were evident in livers from GC-C null mice compared to WT. Collectively these data suggest increased hepatocyte death in the GC-C null mice in the early time period after injury. This corresponds temporally with increased expression of GC-C and its ligands guanylin and uroguanylin in post-injury WT mouse liver. The hepatocyte proliferative response to injury was the same in both genotypes. In contrast, there was no difference in survival between GC-C null and WT mice on the inbred C57BL/6 J background in response to acute liver injury.</p> <p>Conclusions</p> <p>Signalling via GC-C promotes hepatocyte survival <it>in vivo </it>and is required for effective recovery from acute toxic injury to the liver in a strain-specific manner.</p

Anti-Oxidative Effect of Cassia auriculata on Streptozotocin Induced Diabetic Rats

The anti oxidative effect of administration of 100 mg/kg bw and 200 mg/kg bw of the flower powder of Cassia auriculata (CFP) for 45 days to normoglycemic and diabetic rats (streptozotocin induced) was studied. Anti oxidative effect was not observed in normoglycemic rats in the experiment. There was significant (P > 0.05) increase in the level of Thio Barbituric Acid Reactive Substances (TBARS), hydroperoxide and conjugated dienes and significant (P > 0.05) decrease in the catalase, superoxide dismutase and glutathione peroxidase activities and in the level of ascorbic acid, vitamin E and reduced glutathione in diabetic rats. The flower powder of Cassia auriculata significantly (P > 0.05) decreased the TBARS, hydroperoxide and conjugated dienes and increased the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and non enzymic anti oxidants (ascorbic acid, vitamin E and reduced glutathione). The antioxidatve effect of 200 mg/kg bw CFP was significantly (P > 0.05) better than 100 mg/kg bw CFP and the reference drugs (tolbutamide and metformin). The mode of action of CFP remains to be elicited