A possible beneficial effect of metronidazole in reducing TPN-associated liver function derangements

Cholestasis and fatty infiltration of the liver are common complications of total parenteral nutrition (TPN). Following a recent suggestion that TPN-associated liver function derangements may be related to intestinal overgrowth of anaerobic bacteria, the effect of metronidazole on hepatic dysfunction during TPN in rats was investigated. After 5 days of TPN with either amino acids and glucose or amino acids with glucose and fat, all groups exhibited a mild weight gain, positive nitrogen balance, increased liver weight, increased liver:body weight ratio, increased levels of liver enzymes, and increased hepatic lipid content. The administration of metronidazole at 15 mg/kg/day significantly decreased the hepatic lipid content from 0.077 g fat/g liver for controls to 0.053 g fat/g liver. The efficacy of metronidazole in reducing hepatic fat accumulation during nutritionally effective and adequate TPN in rats suggests the possible involvement of anaerobic bacterial flora of the intestinal tract, at least in part, in the pathogenesis of TPN-associated liver function derangements. However, the various biochemical and morphological expressions of these changes and the discrepancy between unchanged liver weight, liver:body weight ratio, liver enzymes, and the improved hepatic fat content suggest multifactorial mechanisms for TPN-related liver damage.