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

• Published in: Journal of Pharmacological Sciences Vol. 108; no. 3; pp. 239 - 247
• Main Authors: Wang, Chien-Chuan, Cheng, Pao-Yun, Peng, Yie-Jen, Wu, Edwin SC, Wei, Hsiao-Ping, Yen, Mao-Hsiung
• Format: Journal Article
• Language: English
• Published: Japan Elsevier B.V 2008; The Japanese Pharmacological Society; Elsevier
• Subjects: Acute Disease; Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; D -galactosamine; Disease Models, Animal; Galactosamine; lipopolysaccharide; Lipopolysaccharides; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mice; Mice, Inbred ICR; naltrexone; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Neutrophils - drug effects; Nitrates - blood; nitric oxide; Nitrites - blood; Superoxides - metabolism; Time Factors; Tumor Necrosis Factor-alpha - blood; tumor necrosis factor-α; D-galactosamine; naltrexone; nitric oxide; lipopolysaccharide; tumor necrosis factor-α
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.08096FP

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.