NUTRITIONAL IMPACT ON THE FINAL OUTCOME OF LIVER-INJURY INFLICTED BY MODEL HEPATOTOXICANTS - EFFECT OF GLUCOSE LOADING

Fifteen percent glucose in drinking water for 7 days increased lethali ty of four structurally and mechanistically different model centrilobu lar hepatotoxicants (acetaminophen, thioacetamide, chloroform, and car bon tetrachloride) in male Sprague-Dawley rats (n = 10/group). A nonle thal injection of thioacetamide was lethal in glucose loaded rats and therefore was chosen for further studies. Serum enzyme elevations and liver histopathology revealed that actual infliction of liver injury p eaked between 36 to 48 h after thioacetamide injection; however, the l iver injury progressed in rats receiving glucose, whereas it regressed in rats maintained on normal diet and drinking water without glucose supplement. Glucose loading did not increase the hepatic microsomal cy tochrome P450. [H-3]thymidine incorporation studies along with prolife rating cell nuclear antigen immunohistochemical analysis of liver sect ions revealed inhibition of S-phase stimulation and decelerated cell c ycle progression. These findings suggest that glucose loading inhibits cellular regeneration and tissue repair resulting in accelerated prog ression of liver injury inflicted by thioacetamide culminating in incr eased death of animals receiving a moderately hepatotoxic dose of thio acetamide.