Vitamin C and E antagonistic effect for tamoxifen-induced rat liver damage: a histopathological, histochemical and ultrastructural studies

ABSTRACT

Tamoxifen is widely used to treat oestrogen dependent carcinoma of the breast. Previous long term studies have shown that oral administration of tamoxifen induces hepatoproliferative lesions and hepatocellular tumors in rats. This study was designed to evaluate the effects of tamoxifen on liver of rats and the possible protective effects of vitamin C and/ or vitamin E in amelioration of these effects. A total of 70 adult female albino rats were used in this study. The animals were divided into seven groups. Each group contained 10 rats. The rats of the first group were kept as control. Animals of the second group were daily dosed orally with tamoxifen 20 mg/ kg b. w. by stomach tube for two weeks. The third group was given vitamin C at dose level of 0.01 g/ 100 g b w by stomach tube, 15 min before daily administration of tamoxifen. The fourth group was given vitamin E at dose level of 100 mg/ kg b.w, 15 min prior to daily administration of tamoxifen throughout the whole period. The fifth group was given combination of the two vitamins [vitamin C and vitamin E] at dose level of 0.01 g/ 100 gb.w. and 100 mg/ kg b.w. respectively, 15 min before daily administration of tamoxifen for two weeks. Each of the remaining two groups was daily given vitamin C [0.01 g/ 100 g b.w.] and/ or vitamin E [100 mg/ kg b.w.] only for two weeks. Paraffin sections were used for the histopathological study. For the histochemical investigations, sections were stained to demonstrate DNA, mucopolysaccharides and protein content. Histopathological effects of tamoxifen were demonstrated in liver as vacuolar degeneration, fatty changes and hydropic degeneration. Signs of degeneration in the form of karyolysis and karyorrhexis were also seen. Moderate dilatation of blood sinusoids, some dysplastic cells and chromalin clumping could be observed. Quantitative DNA image analysis [Lecia image] showed a decrease in DNA content [hypoploidy] in liver of rats treated with tamoxifen only. Tamoxifen induced histochemical changes consisted of marked diminution of protein and mucopolysaccharides content. No histopathological, histochemical and ultra structural changes could be noticed in rats treated with vitamin C and, or vitamin E only. The treatment of rats with vitamin C and/ or vitamin E prior to tamoxifen resulted in amelioration of the histopathological changes of liver as well as histochemical and ultrastructural changes