Naltrexone Protects Against Lipopolysaccharide/D-Galactosamine–Induced Hepatitis in Mice

Journal of Pharmacological Sciences

Edwin SC Wu⁴  Hsiao-Ping Wei¹  Chien-Chuan Wang⁵  Yie-Jen Peng³  Mao-Hsiung Yen²  Pao-Yun Cheng⁶ 

[1] Institute of Toxicology, College of Medicine, National Taiwan University, Taiwan;Department of Pharmacology, National Defense Medical Center, Taiwan;Department of Pathology, Tri-Service General Hospital, Taiwan;Jenken Biosciences, Inc., USA;Department of Psychiatry, Military Kaohsiung General Hospital, Taiwan;Graduate Institute of Chinese Pharmaceutical Sciences, China Medical University, Taiwan

关键词: lipopolysaccharide;    D-galactosamine;    naltrexone;    tumor necrosis factor-α;    nitric oxide;   

DOI  :  10.1254/jphs.08096FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(48)Cited-By(7)Naltrexone, an opioid receptor antagonist, has been claimed to have anti-inflammatory and immunomodulatory effects both in vitro and in vivo. Thus, the aim of this study was to evaluate the effects of naltrexone on acute hepatitis induced by intraperitoneal (i.p.) administration of lipopolysaccharide (LPS, 20 μg/kg)/D-galactosamine (D-gal, 700 mg/kg) in conscious ICR mice. Results demonstrated that post-treatment with naltrexone (20 mg/kg, i.p.) significantly attenuated the deleterious liver function in mice treated with LPS/D-gal. It was also found that naltrexone significantly inhibited the elevation of plasma tumor necrosis factor-α (TNF-α) caused by LPS/D-gal. The overproduction of nitric oxide (NO) and superoxide anions induced by LPS/D-gal were also significantly reduced by naltrexone. Moreover, infiltration of neutrophils into the liver of mice 12 h after treatment with LPS/D-gal was also decreased by naltrexone. In conclusion, the beneficial effects of naltrexone on LPS/D-gal–induced hepatitis result from its inhibition of pro-inflammatory factors and antioxidant effects. Thus, naltrexone is of therapeutic potential for treating liver injury.

【 授权许可】

Unknown