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 lethality of four structurally and mechanistically different model centrilobular hepatotoxicants (acetaminophen, thioacetamide, chloroform, and carbon tetrachloride) in male Sprague-Dawley rats (n = 10/group). A nonlethal 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 peaked between 36 to 48 h after thioacetamide injection; however, the liver 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 cytochrome P450. [3H]thymidine incorporation studies along with proliferating cell nuclear antigen immunohistochemical analysis of liver sections revealed inhibition of S-phase stimulation and decelerated cell cycle progression. These findings suggest that glucose loading inhibits cellular regeneration and tissue repair resulting in accelerated progression of liver injury inflicted by thioacetamide culminating in increased death of animals receiving a moderately hepatotoxic dose of thioacetamide.
Chanda
S
S
Division of Pharmacology and Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University Monroe, 71209-0470, USA.
Mehendale
H M
HM
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002725:Chloroform / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D003643:Death; D005947:Glucose / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*
D018809:Proliferating Cell Nuclear Antigen; D013853:Thioacetamide; D000082:Acetaminophen; D002725:Chloroform; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D005947:Glucose