Liver protection from acetaminophen hepatotoxicity using copper(I)-nicotinic acid complex

Abstract

The present study was performed to investigate the hepatotoxicity of acetaminophen and the possible hepatoprotective effect of copper(I)-nicotinate in rats through biochemical light and electron microscopy studies. Two groups of rats (39 in total) were used: group I (15 rats) received acetaminophen by intraperitoneal injection in a dose of 1000 mg/kg. While group II (15 rats) received an oral dose of 800 μg/kg copper(I)-nicotinate dissolved in 0.5 mL of saline three times through 24 h and 1 h after the last dose, and 9 rats were kept as control. Blood and tissue samples for biochemical, light, and electron microscopy were collected after 4, 12, and 24 h. Biochemical results showed a significant elevation in ALT, AST, and nitric oxide levels in rats who received acetaminophen only. In contrast, the corresponding levels of treated rats with the copper complex showed a less significant elevation in ALT, AST, and nitric oxide. Light microscopic examination of liver tissue taken from intoxicated animals showed congestion of the vasculature with hydropic and fatty degeneration. Centrilobular necrosis of the hepatocytes with glycogen depletion was observed in the centrilobular areas. Ultrastructural examination showed fatty degeneration, mitochondrial swelling, severe irregular dilatation of RER and SER, loss of glycogen granules, and pyknosis of the nuclei. Examination of livers of animals that received copper complex before intoxication revealed only cup-shaped mitochondria, a mild degree of fatty degeneration, and glycogen depletion with no evidence of necrosis. This work provides evidence for the antioxidant properties of the copper(I)-nicotinate complex and illustrates the pathological changes induced by acetaminophen in liver tissue.