Naltrexone protects against lipopolysaccharide/D-galactosamine-induced hepatitis in mice.
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 microg/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-alpha (TNF-alpha) 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.
Wang
Chien-Chuan
CC
Department of Psychiatry, Military Kaohsiung General Hospital, Kaohsiung, Taiwan.
Cheng
Pao-Yun
PY
Peng
Yie-Jen
YJ
Wu
Edwin Sc
ES
Wei
Hsiao-Ping
HP
Yen
Mao-Hsiung
MH
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005688:Galactosamine; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009271:Naltrexone; D005688:Galactosamine