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Abstract
Summary
The present study was performed on 84 albino rats to investigate the effect of acetaminophen hepatotoxicity in rats by means of biochemical and light and electron microscopy studies. Rats were divided into two main groups represented the acute and chronic studies.
Acute experiment included 39 rats. Fifteen rats were injected by acetaminophen (1000 mg/kg I/P). While, the other fifteen rats were treated with an oral dose of 800 μg/kg copper-(I)-nicotinate dissolved in 0.5 ml of saline three times through 24 hours and one hour after last dose, rats were injected with acetaminophen (1000 mg/kg I/P). Nine rats were kept as control. Blood samples and tissue samples for biochemical, light and electron microscopy were taken after 4, 12 and 24 hours from the beginning.
The chronic toxicity study was conducted on 45 rats. Twenty rats received acetaminophen (150 mg/kg I/P) daily and dissected after four weeks. The other twenty rats received copper-(I)-nicotinate in an oral dose of 400 μg/kg dissolved in 0.5 ml of saline once daily orally and one hour later, rats received acetaminophen (150 mg/kg I/P) daily. Rats were dissected after four weeks and samples for biochemical and histopathological studies were taken.
Biochemical results of the acute toxicity study showed a significant elevation in ALT, AST and nitric oxide levels in rats received acetaminophen only in both acute and chronic intoxicated animals. While, the corresponding levels of treated rats with the copper complex showed a less significant elevation in ALT, AST and nitric oxide in both acute and chronic experiments. Glutathione levels measured in the liver tissue showed a significant decline in animals received acetaminophen only at both acute and chronic exposures. While, in animals treated with acetaminophen after treatment with copper complex; level of GSH was more or less within normal level.
Light microscopic examination of liver tissue taken from acute intoxicated animals showed congestion of the vasculature with hyDROPic and fatty degeneration. Peri-acinar necrosis of the hepatocytes with glycogen depletion were observed in the centrilobular areas. Ultrastructural examination showed fatty degeneration, mitochondrial swelling, sever irregular dilatation of RER and SER, loss of glycogen granules and pyknosis of the nuclei.
Examination of livers of acute intoxicated animals prophylacted with copper complex revealed only a mild degree of fatty degeneration and glycogen depletion with no evidence of necrosis. Ultrastructurally, those cells appeared more or less similar to the control animals except for appearance of cup-shaped mitochondria after 24 hours of acetaminophen injection.
Light microscopic examination of chronic intoxicated animals showed increase of collagenous connective tissue formation in portal areas, as well as around the central vein and in the sinusoidal wall. Moreover, mononuclear cell infiltration was observed in the portal area.
Examination of livers of chronic intoxicated animals prophylacted with copper complex revealed no evidence for pathological changes. The hepatocytes of the liver taken from the animals of this group showed marked proliferation of rough endoplasmic reticulum with very prominent cell boundaries. In addition, examination of the hepatocytes of this group revealed intact and healthy membranes.