Role of nutrition in the survival after hepatotoxic injury.
Nutritional status is an important factor in determining susceptibility to toxic chemicals. While macro and micronutrients may affect many aspects of Stage I and Stage II of toxicity, in this paper, the influence of macronutrients as sources of energy required for cell division and tissue repair mechanisms on the outcome of hepatic injury is discussed. 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 structurally and mechanistically different centrilobular hepatotoxicants (acetaminophen, thioacetamide, chloroform and carbon tetrachloride), while male Sprague-Dawley (S-D) rats fed rat chow containing palmitic acid (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 supplemented fatty acids) in drinking water for 7 days were protected from a LD100 dose (600 mg/kg, i.p.) of thioacetamide (TA). Indices of cell division revealed that cell cycle progression in the liver played a very critical role in determining the final outcome of hepatotoxic injury. These results confirmed our hypothesis that cell division and tissue repair play a critical role in survival after life-threatening hepatotoxic 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 decisively 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 enormously to susceptibility of human populations to toxic chemicals.
Chanda
S
S
Division of Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209-0470, USA.
Mehendale
H M
HM
D000284:Administration, Oral; D000818:Animals; D002331:Carnitine / Q000008:administration & dosage; D056486:Chemical and Drug Induced Liver Injury; D004032:Diet; D004326:Drinking / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D008107:Liver Diseases / Q000401:mortality* / Q000503:physiopathology; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D009752:Nutritional Status; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
D010169:Palmitic Acids; D019308:Palmitic Acid; D005947:Glucose; D002331:Carnitine