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Cholestasis caused by the excessive accumulation of bile within the liver, due to intrinsic or extrinsic factors. Cholestasis side effects are associated directly or indirectly with the reduction of bile flow and the confinement of materials related to bile secretion (such as bile acids, bilirubin, and cholesterol). On the other hand, some factors such as opioids, alkaline phosphatase, endotoxin and nitric oxide increase in blood, which could cause tissue damage. Since water intake reduces during cholestasis and hypothalamic nuclei such as paraventricular and supraoptic nucleuses are involved in the regulation of body water; Therefore, in this study, the histopathological changes of hypothalamic nuclei were evaluated. Male Wistar rats weighing 200–250 g were randomly divided into three groups. Three sets of seven groups were unoperated control, sham-operated and bile duct-ligated rats. The tissue samples were analyzed using histotechnique and light microscope. Brain tissue necrosis in paraventricular and supraoptic nucleus in cholestatic rats increased, but in the sham and control rats no changes were observed and also cholestasis caused wrinkle chromatic nuclei and increased thickness of hypothalamic nuclei. Because endotoxin causes tissue trauma, it is likely increased endotoxin may leads to tissue changes in the brain.

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Paclitaxel is a chemotherapy drug inhibiting cell growth. In some studies, patients with normal liver function have experienced increase in bilirubin, ALT and AST by using paclitaxel. The aim of this study was to evaluate the ef-fect of intra-peritoneal injection of doses 5 and 10 mg/kg nZnO on the liver of rats treated with paclitaxel. 35 adult fe-male Wistar rats were divided into 7 groups including control, sham (saline injection), experimental groups1 and 2 (nZnO injection), experimental group 3 (paclitaxel injection), experimental groups 4 and 5 (nZnO and paclitaxel inje-ction). Liver function was examined 28 days after the end of injection. Experimental group3 had large and swollen liver morphology. Most hepatocytes had dense nuclei and changed cell shape indicating of cell death. Blood test showed si-gnificant increase in the levels of ALT, AST and bilirubin and decrease in the level of ALP in comparison with the co-ntrol group. In experimental groups 4 and 5, cell shape alterations, increase in cell death and increase in liver markers were remarkably reduced in comparison with the experimental group 3, in a way that there were no significant differ-ences with the control group. No significant differences were observed between the control group and experimental gr-oups 1 and 2. According to the findings, nZnO can reduce the side effects of paclitaxel on liver tissue.

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Punica granatum leaf extracts have been used since time immemorial in traditional medicines. It is used for its antioxidant properties. Green nanoparticle synthesis is an emerging field which has opened an entirely different scope for medicinal formulations. It has been reported by many users that the green nanoparticles are more effective medicines as compared with their simple extracts. Thus, in order to evaluate these speculations, the present work was undertaken to assess the hepatoprotective activity of silver nanoparticles synthesized using aqueous leaf extract of Punica granatum in comparison with the aqueous extract. After CCl₄ intoxication the serum bilirubin total increased significantly (p<0.05) and the total protein level decreased significantly (p<0.05) as compared with the control group; in addition, alkaline phosphatase activity, aspartate aminotransferase activity and alanine transaminase activity increased significantly (p<0.05). The CCl₄ intoxicated rats were treated with aqueous leaf extract and synthesized nanoparticles, the results clearly revealed that the aqueous extract of Punica granatum showed hepatoprotective effect, as the liver profile altered by CCl₄ toxicity, recovered to normal control values. Moreover, the nanoparticles synthesized using aqueous leaf extract of Punica granatum were comparatively more effective as hepatoprotective agent than the aqueous extract of Punica granatum.