Hepatic encephalopathy (HE) is a syndrome resulting from acute or chronic liver failure. The main hypothesis suggests a state of hyperammonemia which is responsible for both direct and indirect alterations in cerebral metabolism with increased production of reactive oxygen and nitrogen species. The effect of milk-derived alpha-lactalbumin (α-LAC) and vitamin C (vit.C) was evaluated in thioacetamide (TAA)-induced HE model in the current study. Animals were treated with TAA (100 mg/kg, i.p.) or saline thrice weekly for six weeks to induce HE then treatment groups received orally α-LAC (100 or 150 mg/kg) and /or vit.C (500 mg/kg) daily for two weeks. Twenty-four hours after last treatment sera, liver and brain samples were collected to assess serum ammonia level, activities of alanine transaminase (ALT), and aspartate transaminase (AST), brain and liver oxidative stress parameters as well as histopathological investigations. TAA rats experienced increases in serum activities of ALT and AST as well as serum levels of ammonia. Furthermore, TAA induced hepatic and brain oxidative damage as indicated by increase in lipid peroxidation (LP), decrease in reduced glutathione (GSH) and decrease in superoxide dismutase (SOD) activity as well as increased nitric oxide (NO) levels. TAA caused distortion of hepatic and brain architecture as shown by histopathological examination. Treatment with α-LAC either alone or combined with vit.C resulted in improved liver functions by decline in serum AST and ALT activities and reduction in serum ammonia level. Alpha-LAC and vit.C reduced LP and NO levels while increased GSH concentration and SOD activity in hepatic and brain tissues. Finally, α-LAC-vit.C combination improved the hepatic and brain histological picture. Alpha-LAC-vit.C combination may be a promising pharmacological tool in providing a natural source of branched-chain amino acids and powerful antioxidants to combat hepatic encephalopathy-associated hyperammonemia and its consequential oxidative damage in liver and brain.
Key words: Alpha-Lactalbumin, Vitamin C, Thioacetamide, Liver, Brain, Ammonia, Oxidative Stress, Hepatic Encephalopathy, Rats.
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