Vitamin E deficiency and peripheral nerve injury induced by cholestasis: an animal experimental study
ZHAN Xue, WANG Shao-Ying, CAI Fang-Cheng, ZHANG Xiao-Ping, XIAO Ping
Department of Infectious Diseases and Gastroenterology, Children's Hospital Affiliated to Chongqing University of Medical Sciences, Chongqing 400014, China. zhanxue@hotmail.com
Abstract OBJECTIVE: To determine whether there is an association between low serum concentrations of vitamin E (VitE) and peripheral nerve injury, and to investigate the therapeutic effects of VitE supplementation on peripheral nerve and hepatic injury induced by cholestasis. METHODS: Thirty 2-day-old Wistar rats were randomly assigned into 3 groups: Untreated hepatopathy group, VitE-treated hepatopathy group and Normal control group (n=10 each).Cholestatic hepatopathy was induced by gastric lavage with α-Naphthyl isothiocyanate (ANIT, 60 mg/kg,once every two days for 6 weeks) in rats. The VitE-treated group received additionally VitE by gastric lavage (70 IU/kg, once daily for 6 weeks).Serum VitE concentration was measured by high-performance liquid chromatography. Serum concentrations of total bilirubin (TB), direct bilirubin (DB) and alanine aminotransferase (ALT) were measured by automated biochemical analyzers. The histopathological changes of liver and sciatic nerves were observed under light and electronic microscopes. Average areas of liver lesions were measured by automated image analysis. RESULTS: In Untreated hepatopathy group the serum DB concentration increased by 62.4 times and the serum TB concentration increased by 30.0 times compared with those of the Normal control group. Serum concentrations of DB and TB in the VitE-treated group were much lower than those of Untreated hapatopathy group, although they were higher than those of the Normal control group. The extent of necrosis and fibrosis in the liver of the Untreated hepatopathy group was significantly larger than in the VitE-treated group. The Untreated hepatopathy group showed lower serum VitE concentrations than the Normal control group (P=0.004). VitE treatment significantly increased the serum VitE concentrations, to the same as Normal control group. Pathologic changes were observed in the sciatic nerves in the Untreated hepatopathy group, including axonal degeneration and demyelination. VitE treatment significantly reduced the extent of pathologic changes in the sciatic nerves. The Untreated hepatopathy group had significantly more nerve transections with severe lesions than the VitE-treated group. CONCLUSIONS: VitE deficiency may be the dominant cause of peripheral nerve injury in cholestatic hepatopathy. VitE treatment can effectively reduce the extent of peripheral nerve injury, decrease serum concentrations of TB and DB, and reduce the extent of liver injury and fibrosis induced by cholestatic hapatopathy.
ZHAN Xue,WANG Shao-Ying,CAI Fang-Cheng et al. Vitamin E deficiency and peripheral nerve injury induced by cholestasis: an animal experimental study[J]. 中国当代儿科杂志, 2005, 7(4): 357-361.
ZHAN Xue,WANG Shao-Ying,CAI Fang-Cheng et al. Vitamin E deficiency and peripheral nerve injury induced by cholestasis: an animal experimental study[J]. CJCP, 2005, 7(4): 357-361.
