Acute and chronic hyperammonemia modulate antioxidant enzymes differently in cerebral cortex and cerebellum.
Studies on acute hyperammonemic models suggest a role of oxidative stress in neuropathology of ammonia toxicity. Mostly, a low grade chronic type hyperammonemia (HA) prevails in patients with liver diseases and causes derangements mainly in cerebellum associated functions. To understand whether cerebellum responds differently than other brain regions to chronic type HA with respect to oxidative stress, this article compares active levels of all the antioxidant enzymes vis a vis extent of oxidative damage in cerebral cortex and cerebellum of rats with acute and chronic HA induced by intra-peritoneal injection of ammonium acetate (successive doses of 10 x 10(3) & 8 x 10(3) micromol/kg b.w. at 30 min interval for acute and 8 x 10(3) micromol/kg b.w. daily up to 3 days for chronic HA). As compared to the respective control sets, cerebral cortex of acute HA rats showed significant decline (P < 0.01-0.001) in the levels of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) but with no change in glutathione reductase (GR). In cerebellum of acute HA rats, SOD, catalase and GR though declined significantly, GPx level was found to be stable. Contrary to this, during chronic HA, levels of SOD, catalase and GPx increased significantly in cerebral cortex, however, with a significant decline in the levels of SOD and GPx in cerebellum. The results suggest that most of the antioxidant enzymes decline during acute HA in both the brain regions. However, chronic HA induces adaptive changes, with respect to the critical antioxidant enzymes, in cerebral cortex and renders cerebellum susceptible to the oxidative stress. This is supported by approximately 2- and 3-times increases in the level of lipid peroxidation in cerebellum during chronic and acute HA respectively, however, with no change in the cortex due to chronic HA.
Biochemistry & Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Santosh
S
Singh
Raj K
RK
Koiri
Surendra Kumar
SK
Trigun
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology*; D002908:Chronic Disease; D004591:Electrophoresis, Polyacrylamide Gel; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D022124:Hyperammonemia / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase