Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats

Aim: The aim of this study was to investigate the hypothesis that the opioid system is involved in the development of hepatic fibrosis. Methods: The effect of naltrexone (an opioid receptor antagonist) on hepatic fibrosis in bile duct ligated (BDL) or sham rats was assessed by histology and hepatic hydroxyproline levels. Liver matrix metalloproteinase 2 (MMP-2) was measured by zymography, and α smooth muscle actin (α-SMA) and CD45 (leucocyte common antigen) by immunohistochemistry. The redox state of the liver was assessed by hepatic glutathione (GSH)/oxidised glutathione (GSSG) and S-nitrosothiol levels. Subtypes of opioid receptors in cultured hepatic stellate cells (HSCs) were characterised by reverse transcriptase-polymerase chain reaction, and the effects of selective δ opioid receptor agonists on cellular proliferation, tissue inhibitor of metalloproteinase 1 (TIMP-1), and procollagen I expression in HSCs determined. Results: Naltrexone markedly attenuated the development of hepatic fibrosis as well as MMP-2 activity (p