Role of Intrarenal Biotransformation in Chloroform-Induced Nephrotoxicity in Rats

Details

• Personal Author:
  Hewitt WR ; Hook JB ; Smith JH
• Description:
  Various ketonic agents potentiate the hepatic and renal toxicity of halogenated solvents in mice and rats. Characteristics of CHCl3 nephrotoxicity and of 2-hexanone potentiation were evaluated in adult male Fischer 344 rats pretreated with vehicle (oil, 10 ml/kg, po) or 2-hexanone (10 mmol/kg, po) 18 hr prior to CHCl3 exposure. In contrast to the liver, little metabolism of 14CHCl3 by renal cortical microsomes from vehicle- or 2-hexanone-pretreated rats was detected. However, CHCl3 produced a concentration-related dysfunction when added to renal cortical slices from Fischer 344 or Sprague-Dawley rats. The degree of CHCl3 toxicity in vitro was not altered when renal cortical slices were preincubated with CHCl3 (8.5 microl) under an atmosphere of carbon monoxide. In renal cortical slices, deuterated-CHCl3 was less toxic than CHCl3. Although 2-hexanone pretreatment increased renal slice metabolism of 14CHCl3 twofold, this increase was not associated with an increase in nephrotoxicity after direct exposure of slices to CHCl3 (0 to 10 µl) in vitro. CHCl3 (0.5 ml/kg, ip) did not alter renal cortical glutathione concentrations in vehicle or 2-hexanone pretreated rats. The association of 14CHCl3-derived radiolabel was increased over control by 2-hexanone pretreatment in protein, lipid, and acid soluble fractions from the renal cortex by approximately two-, two-, and fivefold, respectively. In conclusion, renal cytochrome P-450 did not appear to mediate CHCl3 metabolism and nephrotoxicity in the rat to the extent observed previously in mice. 2-Hexanone appeared to potentiate nephrotoxicity by a mechanism different than that observed in rat liver. [Description provided by NIOSH]
• Subjects:
  Animals Occupational Health Safety Toxicology
• Keywords:
  Animal Studies Biotransformation Chloroform Kidney Toxins Liver Tissue Renal Toxicity Toxic Effects
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; Missouri ; OSHA Region 5 ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  166-174
• Volume:
  79
• Issue:
  1
• NIOSHTIC Number:
  nn:20060497
• Citation:
  Toxicol Appl Pharmacol 1985 Jun; 79(1):166-174
• Contact Point Address:
  Jerry B. Hook, Department of Investigative Toxicology, Smith Kline & Frenh Laboratories, Philadelphia, Pa. 19101
• CAS Registry Number:
  Chloroform (CAS RN 67-66-3)
• Federal Fiscal Year:
  1985
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7a94a1d58e6f7238e4b159e2708ced9e6dfa4b2f573a186bfbbb418876c59d0f87dabb93e817e4b7a09368d6ccbda543a72730740c8345aa60e16871a2e3aa84
• Download URL:
  https://stacks.cdc.gov/view/cdc/224372/cdc_224372_DS1.pdf
• File Type:
  [PDF - 765.81 KB ]