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Yi-Sheng Liu, Wei Cai, Sheng-Mei Wu, Long-Hua Qian
Shanghai, China
Author Affiliations: Xinhua Hospital Affiliated to Medical School, Shanghai Jiaotong University, Shanghai Institute for Pediatric Research, Shanghai 200092, China (Liu YS, Cai W, Wu SM, Qian LH)
Corresponding Author: Yi-Sheng Liu, MD, PhD, Xinhua Hospital Affiliated to Medical School, Shanghai Jiaotong University, Shanghai Institute for Pediatric Research, Shanghai 200092, China (Tel: 86-21-65790000 ext 3426; Fax: 86-21-65791316; Email: liuyisheng2002@yahoo.com.cn)
Background: Total parenteral nutrition (TPN) has been used clinically for more than 30 years, but hepatobiliary complications associated with TPN remain to be solved. The aim of this study was to investigate the effect of S-adenosylmethionine (SAMe) on TPN-induced cholestasis and hepatocytic apoptosis.
Methods: Twenty-four newborn rabbits were randomly divided into 3 groups: normal control group receiving breast milk, TPN group receiving TPN at a dose of 200 kcal/kg per day, and SAMe group receiving TPN plus SAMe at an intravenous dose of 100 mg/kg per day. Blood and liver samples were collected one week later. The levels of serum bile acid, alanine aminotransferase (ALT), alkaline phosphatase (AKP), total bilirubin, direct reaction bilirubin, albumin and globulin levels were detected by an automatic biochemical analyzer. Hepatic pathological changes were observed under the light microscope, and apoptosis of hepatocytes was determined with the TUNEL method.
Results: There were no significant differences in the levels of serum bile acid, ALT, AKP, total bilirubin, albumin and globulin between the SAMe group and control group (P>0.05). The level of direct reaction bilirubin in the SAMe group was obviously higher than that in the control group (P<0.01), but significantly lower than that in the TPN group (P<0.01). Cholestatic changes and mild hepatic steatosis were observed in the TPN group, while no such changes were found in the SAMe and control groups. The apoptotic cell counts were 0.263%¡À0.041% in the control group, 1.060%¡À0.217% in the TPN group, and 0.467%¡À0.182% in the SAMe group. The apoptotic cells were much more in the TPN group than in the control (P<0.01) and SAMe groups (P<0.05).
Conclusions: TPN can cause cholestasis and increase apoptosis of hepatocytes in newborn rabbits. SAMe can prevent TPN-induced cholestasis effectively, and the inhibition of hepatocytic apoptosis may be one of its mechanisms.
Key words: S-adenosylmethionine; total parenteral nutrition; apoptosis; cholestasis; steatosis; newborn World J Pediatr 2007;3(3):218-221
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