title: Nutritional modulation of the final outcome of hepatotoxic injury by energy substrates: an hypothesis for the mechanism.
abstract: Survival after hepatocellular injury and necrosis may depend on the ability of the remaining hepatocytes to divide and restore an adequate population of functioning cells. Although adequate nutritional support is necessary for liver regeneration after severe liver damage, much is yet to be discovered concerning which nutritional factors are critical for liver regeneration. Clinically, nutritional substances are administered only from the energy aspect, without regard to whether or how these substrates may facilitate or impede liver tissue repair processes. Glucose is used as principal source of energy in liver damage because of accompanying marked hypoglycemia. But the contribution of glucose to compensatory liver regeneration and/or survival is unclear. This paper advances the hypotheses that: (1) glucose increases the toxicity of centrilobular hepatotoxicants by inhibiting hepatic cell division and tissue repair allowing unrestrained progression of injury; (2) fatty acids facilitate hepatic-cell division permitting hepatolobular restoration to occur thus preventing death from even a lethal dose. If hepatic tissue repair can be stimulated by some therapeutically compatible mechanism, then it might be possible to prevent death from even massive hepatocellular injury. In addition to nutritional manipulation, it should be possible to exploit molecular mechanisms that regulate organized cell division (tissue repair) to increase survival rates of patients suffering from fulminant hepatic failure. These findings have significant impact on tissue repair in a variety of other organs and tissues, particularly in diabetes-like conditions.
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chanda
authors.forename: H M
authors.initials: HM
authors.lastname: Mehendale
authors.forename: S
authors.initials: S
authors.lastname: Chandra
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology*; D005217:Fat Emulsions, Intravenous; D005260:Female; D005950:Glucose Solution, Hypertonic / Q000008:administration & dosage; D006801:Humans; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D009751:Nutritional Requirements; D010288:Parenteral Nutrition; D051381:Rats
chemical_list: D005217:Fat Emulsions, Intravenous; D005950:Glucose Solution, Hypertonic