Hepatoprotection by dimethyl sulfoxide. I. Protection when given twenty-four hours after chloroform or bromobenzene

Dimethyl sulfoxide (DMSO) has previously been repot ted to protect against hepatotoxicity resulting from chloroform (CHCl3) or bromobenzene (BB) when given 10 hr after the toxicant. The object of these studies was to further demonstrate the latent protective ability of DMSO by administering it at a much later time (24 hr) following toxicant exposure. In addition, a more de tailed evaluation of the lesions was performed to better characterize the l esion progression and resolution. Male Sprague-Dawley rats received a hepat otoxic oral dose of either CHCl3, (1.0 ml/kg) or BE (0.5 ml/kg) and then re ceived 2 ml/kg DMSO intraperitoneally 24 hr later. With both toxicants, lim ited centrilobular lesions were already present by the time DMSO was admini stered. Without treatment, liver injury rapidly progressed so that by 48 hr it occupied 40-50% of the liver, with accompanying large increases in plas ma alanine aminotransferase (ALT) activity. Administration of DMSO greatly attenuated lesion development for both toxicants; the area injured was redu ced by more than 4-fold, accompanied by a decrease in 48 hr ALT activity of 8-16-fold. The ability of DMSO to intervene in the development of liver in jury at such a late time appears to be unique and may provide insight into therapies for acute xenobiotic-induced hepatitis.