Carnosine Supplementation Mitigates Brain Tissue Markers of Oxidative Stress in a Rat Model of Fulminant Hepatic Failure
Fulminant hepatic failure is a deleterious clinical complication, which leads to hyperammonemia. Ammonia is a noxious neurotoxic agent, which affects brain tissue through different mechanisms. On the other hand, it is well-known that oxidative stress and its consequences play a major role in the pathogenesis of ammonia-induced brain injury. Carnosine is a dipeptide abundantly found in the human central nervous system (CNS). This peptide is widely investigated for its neuroprotective properties. The current study aimed to evaluate the effect of carnosine supplementation on oxidative stress markers in the brain tissue of a rat model of fulminant hepatic failure and hyperammonemia. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. On the other hand, brain tissue markers of oxidative stress including reactive oxygen species (ROS) formation, lipid peroxidation, tissue glutathione content, and total antioxidant capacity were measured. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including ROS formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was evident in the brain of thioacetamide-treated animals. It was found that carnosine supplementation (250, 500, and 1000 mg/kg) decreased serum markers of liver injury, mitigated brain, and plasma ammonia level, and alleviated brain tissue markers of oxidative stress. These data suggest carnosine as a potential neuroprotective agent with therapeutic capability against ammonia-induced CNS injury.
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