Possible Protective Effect of Certain Flavonoid against Flutamide-Induced Hepatotoxicity in Adult Male Rats.
Aml Salem Saleh Ahmed;
Abstract
Flutamide, a non-steroidal anti-androgenic anilide compound, is widely used for the treatment of prostatic cancer. It is an idiosyncratic hepatotoxicant that sometimes results in severe liver toxicity. It shows a photo hemolytic effect on human erythrocytes and photo induces lipid peroxidation. Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of free radical mediated diseases. Morin, a member of flavonols, exerts antioxidant potential and offers protection against the oxidative stress induced by hydrogen peroxide. The present study aimed to investigate the protective effect of morin against flutamide on the rat liver. Seventy male albino rats weighing 190-200 g were used to study the biochemical analysis of liver function parameters, including ALT, AST, direct and total bilirubin activities in the blood sera and MDA, SOD, GSH and GST in liver tissue.
In addition, the histological alterations and histochemical changes, including polysaccharides and total proteins in liver tissues were investigated, as well as studying the electron microscopic alterations. The experimental animals were divided into seven groups, 10 rats each, and treated as follows: 1) rats did not receive any treatment (control group); 2) rats received 0.5 ml of carboxy methyl cellulose (CMC, 0.5%) for 8 weeks (vehicle group); 3) rats received CMC for 4 weeks then 50 mg morin / kg b.w. for other 4 weeks (CM group); 4) rats received 50 mg morin / kg b.w. for 8 weeks (morin group); 5) rats received CMC for 4 weeks followed by treatment with 100 mg flutamide/ kg b.w. for additional 4 weeks (CFgroup); 6) rats received CMC for 4 weeks then received 50 mg morin/ kg b.w.+ 100 mg flutamide/ kg b.w. for another 4 weeks (CMF group) and 7) rats received 50 mg morin/ kg b.w. for 4 weeks then received 50 mg morin/ kg b.w.+ 100 mg flutamide/ kg b.w. for extra 4 weeks (MMFgroup). Rats received their respective doses daily by oral gavage.
The results of the present study in flutamide group revealed that the mean final body weight decreased; meanwhile, the absolute and relative liver weights increased. There was a very highly significant increase in ALT, AST, direct and total bilirubin activities in serum while, in the hepatic tissue there was an increase in MDA and a decrease in SOD, GSH and GST levels.
The histopathological studies displayed deleterious alterations in the liver tissue where flutamide caused distortion of hepatic architecture with swollen vacuolar hyaline degeneration, atrophy and necrosis of hepatocytes. Some nuclei of the degenerated cells showed pyknosis and the other showed karyolysis. Inflammatory cellular infiltration in addition to congestion and dilatation of the blood vessels were also detected. Histochemical studies revealed that flutamide alone decreased polysaccharides and total proteins in the liver tissue. These changes were confirmed at ultrastructural level, including pyknotic nuclei as well as irregular nuclear envelopes, swollen mitochondria with ill-differentiated cristae, fragmented rough endoplasmic reticulum and increased collagenous fibrils manifesting early sign of fibrosis.
In addition, the histological alterations and histochemical changes, including polysaccharides and total proteins in liver tissues were investigated, as well as studying the electron microscopic alterations. The experimental animals were divided into seven groups, 10 rats each, and treated as follows: 1) rats did not receive any treatment (control group); 2) rats received 0.5 ml of carboxy methyl cellulose (CMC, 0.5%) for 8 weeks (vehicle group); 3) rats received CMC for 4 weeks then 50 mg morin / kg b.w. for other 4 weeks (CM group); 4) rats received 50 mg morin / kg b.w. for 8 weeks (morin group); 5) rats received CMC for 4 weeks followed by treatment with 100 mg flutamide/ kg b.w. for additional 4 weeks (CFgroup); 6) rats received CMC for 4 weeks then received 50 mg morin/ kg b.w.+ 100 mg flutamide/ kg b.w. for another 4 weeks (CMF group) and 7) rats received 50 mg morin/ kg b.w. for 4 weeks then received 50 mg morin/ kg b.w.+ 100 mg flutamide/ kg b.w. for extra 4 weeks (MMFgroup). Rats received their respective doses daily by oral gavage.
The results of the present study in flutamide group revealed that the mean final body weight decreased; meanwhile, the absolute and relative liver weights increased. There was a very highly significant increase in ALT, AST, direct and total bilirubin activities in serum while, in the hepatic tissue there was an increase in MDA and a decrease in SOD, GSH and GST levels.
The histopathological studies displayed deleterious alterations in the liver tissue where flutamide caused distortion of hepatic architecture with swollen vacuolar hyaline degeneration, atrophy and necrosis of hepatocytes. Some nuclei of the degenerated cells showed pyknosis and the other showed karyolysis. Inflammatory cellular infiltration in addition to congestion and dilatation of the blood vessels were also detected. Histochemical studies revealed that flutamide alone decreased polysaccharides and total proteins in the liver tissue. These changes were confirmed at ultrastructural level, including pyknotic nuclei as well as irregular nuclear envelopes, swollen mitochondria with ill-differentiated cristae, fragmented rough endoplasmic reticulum and increased collagenous fibrils manifesting early sign of fibrosis.
Other data
| Title | Possible Protective Effect of Certain Flavonoid against Flutamide-Induced Hepatotoxicity in Adult Male Rats. | Other Titles | التأثير الوقائى المحتمل للفلافونويد ضدالتسمم الكبدى المستحدث بمادة فلوتاميد فى ذكور الجرذان البالغة. رسالــة مقدمة للحصـول على درجة دكتوراه الفلسفة في العلوم (علم الحيوان) | Authors | Aml Salem Saleh Ahmed | Issue Date | 2015 |
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