Temporal analysis of rat liver injury following potentiation of carbon tetrachloride hepatotoxicity with ketonic or ketogenic compounds.
The administration of some ketonic or ketogenic compounds prior to a challenging dose of CCl4 potentiates the hepatic damage induced by this haloalkane. However, nothing is known about the recovery from the liver injury in these cases of chemically induced potentiation. To investigate this problem, we performed a temporal analysis of the hepatotoxic response of male Sprague-Dawley rats to CCl4 following a single pretreatment (p.o.) with: n-hexane, 2-hexanone, 2,5-hexanedione (15 mmol/kg in corn oil), isopropanol, acetone (33 and 34 mmol/kg in water, respectively); or the vehicle alone (10 ml/kg). They received, 18 h later, an i.p. injection of CCl4 (0.1, 0.75 or 1.0 ml/kg) and were killed 24-120 h later. Liver damage was assessed biochemically (ALT, OCT) and morphologically. A good correlation between biochemical and morphological results was observed. The ketonic or ketogenic compounds studied potentiated the liver injury produced by 0.1 ml/kg CCl4. Relative ranking orders regarding severity of maximal hepatic damage induced and time needed for complete recovery of liver injury were established; time of recovery was dependent on the maximal severity of the lesion, regardless of the potentiation. The results show that the temporal evolution of CCl4-induced liver injury is not markedly influenced by the administration of ketonic or ketogenic compounds as pretreatments, but rather depends on the severity of the maximal damage induced by the overall treatment.
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004357:Drug Synergism; D007659:Ketones / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007659:Ketones; D002251:Carbon Tetrachloride; D009954:Ornithine Carbamoyltransferase; D000410:Alanine Transaminase