On the Protective Effects of IMOD and Silymarin Combination in a Rat Model of Acute Hepatic Failure Through Anti Oxidative Stress Mechanisms
Hepatoprotective effect and mechanisms of a novel selenium/electromagnetically treated multiherbal mixture named Setarud (IMODTM) in combination with silymarin (SM) a known hepatoprotective compound was investigated in acetaminophen-induced acute hepatic failure rat model. Animals were divided into five groups and pre-induced with phenobarbital (0.1 mg kg-1, i.p.) before administration of a single dose of acetaminophen (1 g kg-1, i.p.) except group 1 which was considered as normal. Group 2 was remained without treatment and considered as control while groups 3 to 5 were treated with SM (50 mg kg-1, p.o.), IMOD (30 mg kg-1, i.p.) and IMOD+SM, respectively 24 h post administration of acetaminophen. Blood was collected at 0, 24 and 72 h post acetaminophen treatment. Elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) confirmed hepatic failure induced by acetaminophen. After 48 h of treatment, the rats were anesthetized and the liver was removed and the right lobule was homogenized and then measured for catalase (CAT), malondialdehyde (MDA) and glutathione (GSH) value. Part of liver was left in paraffin for histopathology examination. CAT and GSH were significantly decreased in the acetaminophen-treated group while ALT, AST, ALP and MDA increased when compared to normals. Histopathological examination of acetaminophen-treated animals showed necrosis, inflammation, hyperplasia of kupffer and infiltration of mononuclear cells, dilation of sinusoids and disruption of hepatocytes, while treatment with IMOD+SM normalized protected hepatic architecture in accordance to biochemical results. Treatment of animals with IMOD and SM alone or in combinations considerably protected the hepatic failure by diminishing ALT, AST, ALP and MDA. Both IMOD and SM and their combination improved acetaminophen-induced histopathological hepatic damage. Conclusion is that combination of IMOD and SM considerably protect from acute hepatic failure via enzymatic and non-enzymatic mechanisms.
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