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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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In cholestasis syndrome, the change of bile acids, salts, endotoxins and opioidsis is accompanied with hepaticencephalopathy and brain trauma; therefore, in this study, the histopathological changes of hippocampus after bile duct ligation were investigated. This study was performed on male Wistar rats. The rats were divided into three groups, namely the control, sham and cholestatic groups. After two weeks, the rats were killed under anesth-esia and their brains were dissected with no delay. The specimens were processed routinely and were sectioned into slices of 6-micron thickness. The sections were stained by Hematoxiline-Eosin (H&E) method. Subsequently, they were studied using optical microscope. Necrotic cells, the diminution of cell density and wrinkled chromatic nuclei were observed in hippocampus section. In addition, the thickness of hippocampus was mostly decreased. However, in the sham and control groups no changes were observed. Since endotoxin causes tissue trauma, the increase of en-dotoxin may result in tissue changes in the brain.

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Several therapeutic effects have been reported for Peganum harmala and Piper longum. These plants contain flavonoids that probably can affect reproductive endocrine system and reduce fertility. In this study, the impacts of hydroalcoholic extracts of Peganum harmala and Piper longum on pituitary-gonadal axis were investigated. Male mice were divided into one control group and three experimental groups. The first experimental group received the extract of Peganum harmala (200 mg/lit), while the second experimental group received the extract of Piper longum (200 mg/lit) and the third experimental group received the combination of both extracts (200 mg/lit) for 30 days. After the treatment, spermatogonia, spermatocytes and spermatids were counted and serum levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. Data were analyzed by SPSS software. Levels of testosterone, FSH and LH showed a significant decrease in the first and third experimental groups in comparison with the control group. Moreover, the number of spermatogonia, spermatocyte and spermatid decreased in these groups. The results of the present study demonstrated that hydroalcoholic extract of Peganum harmala and Piper longum can decrease the pituitary gonadal axis function and spermatogenesis in male NMRI mice.
 

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Impaired motor functions were reported in cholestatic animals. This disorder in the function and death of motor neurons is highly dependent on changes in the environment around astrocytes and the blood-brain barrier, which is moderated by the aquaporin 4 protein. For this reason, the effects of cholestasis on motor cortex histology and morphology and aquaporin 4 protein levels were investigated in this study. Samples were stained by hematoxylin-eosin method. Histological changes in cortical brain were investigated. The amount of AQP4 protein in control, sham, and experimental groups were tested by immunohistochemistry. The thickness of motor cortex in cholestatic samples increased in comparison with the control and sham groups. Also, cholestasis caused wrinkle chromatic nuclei. On the other hand, tissue necrosis was detected in cholestatic group compared with sham and control groups. Reduction of cells densities in some cortical layers has been observed, which is probably indicative of cholestasis-induced cell death. AQP4 expression significantly decreased in BDL (p <0.05), but not in other groups (P<0.05). In this study, the pathology of motor cortex, which has also been associated with the decrease of neurons, could be considered the cause of motion abnormalities and AQP4 level reduction in cholestatic rats.