Dimethyl sulfoxide inhibits dimethylnitrosamine-induced hepatic fibrosis in rats

We studied the preventive effects of dimethyl sulfoxide (DMSO) on experimen tal hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatmen t with DMN caused a significant decrease in body and liver weight. Oral DMS O (2 ml/kg daily for 4 weeks) essentially prevented this DMN-induced body a nd liver weight loss with no major side effects. DMSO suppressed the induct ion of hepatic fibrosis, as determined by histological evaluation, and redu ced hepatic hydroxyproline. It also suppressed the expression of mRNA for t ype I collagen in the liver. Because hepatic stellate cells (HSC) are the m ajor cellular source of the collagen in hepatic fibrosis, we examined the e ffects of DMSO on collagen production in vitro using rat primary HSC cultur e. However, it was found that DMSO did not inhibit the collagen production in vitro. We next evaluated the effects of DMSO on tumor necrosis factor al pha (TNF alpha) and nitric oxide (NO) production by Kupffer cells, because these factors represent major activator of HSC, and because monocyte-macrop hage infiltration has been implicated as being pathogenetically important f or hepatic fibrosis induced by DMN. DMSO inhibited lipopolysaccharide (LPS) -induced TNF alpha and NO production, and reduced TNF alpha mRNA levels. DM SO also suppressed the LPS-induced nuclear factor kappa B activation in a m urine macrophagelike cell line. These results suggest that the inhibitory e ffects of DMSO on hepatic fibrosis may be primarily exerted via blocking of DMN-induced inflammation. These results also implied that DMSO may be pote ntially useful for preventing the development of hepatic fibrosis.