Acetone potentiation of chronic liver injury induced by repetitive administration of carbon tetrachloride

Abstract

The ability of ketonic compounds to modify the chronic liver injury (cirrhosis) induced by haloalkanes is unknown. To investigate this problem, male Sprague-Dawley rats were treated p.o. twice weekly for 12 weeks with acetone (25 mmoles per kg in corn oil) or corn oil alone (10 ml per kg). The rats were treated p.o. with corn oil (10 ml per kg) or CCl₄ (5 mmoles per kg in corn oil) 18 hr after each pretreatment. Animals were killed after 4, 8, 10 or 12 weeks of treatment. Liver-kidney/body weight ratios were computed; biochemical analyses were performed on plasma (ALT, bilirubin and blood urea nitrogen) and liver (collagen) samples. For the 10-week group, liver injury was assessed by a morphometric analysis. Body weight gain was slower in acetone-treated rats given CCl₄;35% died. Compared to corn oil + CCl₄-treated rats, acetone + CCl₄-treated animals showed significantly lower liver weight/body weight ratios and higher kidney weight/body weight ratio values at all four times. Significantly higher levels occurred at all four times for bilirubin concentrations, and at 4, 8 and 10 weeks for collagen contents. No significant differences were observed in ALT activities between corn oil- and acetone-treated rats challenged with CCl₄. Light microscopy revealed that after 10 weeks of treatment, acetone + CCl₄-treated animals showed a fully developed cirrhosis, whereas a much less severe lesion was observed in corn oil + CCl₄-treated rats. Evidence of nephrotoxicity was observed in the acetone + CCl₄ group as exemplified by significantly elevated blood urea nitrogen values. We conclude that acetone treatment increases the extent of fibrosis and accelerates the appearance of cirrhosis induced by CCl₄.