ROLE OF NUTRITION IN THE SURVIVAL AFTER HEPATOTOXIC INJURY

Nutritional status is an important factor in determining susceptibilit y to toxic chemicals. While macro and micronutrients may affect many a spects of Stage I and Stage II of toxicity, in this paper, the influen ce of macronutrients as sources of energy required for cell division a nd tissue repair mechanisms on the outcome of hepatic injury is discus sed. Male Sprague-Dawley rats maintained on normal rodent chow and 15% glucose (as a source of energy for the centrilobular hepatocytes) in drinking water for 7 days experienced an increased lethality from stru cturally and mechanistically different centrilobular hepatotoxicants ( acetaminophen, thioacetamide, chloroform and carbon tetrachloride), wh ile male Sprague-Dawley (S-D) rats Fed rat chow containing palmitic ac id (PA, 8% w/w, as a source of energy for the periportal hepatocytes) and L-carnitine (LC, 2 mg/ml, as a mitochondrial carrier for the suppl emented fatty acids) in drinking water for 7 days were protected from a LD(100) dose (600 mg/kg, i.p.) of thioacetamide (TA). Indices of cel l division revealed that cell cycle progression in the liver play a ve ry critical role in determining the final outcome of hepatotoxic injur y. These results confirmed our hypothesis that cell division and tissu e repair play a critical role in survival after life-threatening hepat otoxic injury. Any manipulation directed towards altering a prompt and exacting compensatory cell division and tissue repair responses after hepatotoxic injury would also alter the final outcome of the toxicity . These studies indicate that the source of cellular energy can decisi vely influence the compensatory response of the target tissue to alter the outcome of hepatotoxic injury. Since nutritional status is known to vary widely among human populations, these could contribute enormou sly to susceptibility of human populations to toxic chemicals.