Studies on the mechanism of toxicity of reduced lantadene a in rats

Pass M.A., Pugh M.W. and Findlay L. (1981) Studies on the mechanism of toxicity of reduced lantadene a in rats. Biochemical Pharmacology, 30 12: 1433-1437. doi:10.1016/0006-2952(81)90363-4

Author Pass M.A.
Pugh M.W.
Findlay L.
Title Studies on the mechanism of toxicity of reduced lantadene a in rats
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 1981-06-15
Sub-type Article (original research)
DOI 10.1016/0006-2952(81)90363-4
Volume 30
Issue 12
Start page 1433
End page 1437
Total pages 5
Subject 3004 Pharmacology
Abstract Experiments were performed to test the effects of some hepatic enzyme inducers and inhibitors on the hepatotoxicity of the triterpene acid reduced lantadene A in rats, and to determine the relationship of injury of bile canaliculi to the onset of cholestasis. Pretreatment of female Wistar rats with phenobarbitone, SKF525A or carbon disulphide failed to alter the toxicity of reduced lantadene A but when female rats were pretreated with spironolactone there was a marked increase in the severity of toxicity. Male rats which are normally resistant to the toxicity of reduced lantadene A were still resistant after pretreatment with spironolactone. In other experiments rats were sacrificed at various times after dosing with reduced lantadene A and liver plasma membrane fractions enriched in bile canaliculi were prepared for estimation of the activities of 5'-nucleotidase and Mg2+-ATPase. The activity of 5'-nueleotidase was reduced at 4 hr after administration of reduced lantadene A and by 6 hr the activities of both enzymes were significantly reduced. At 24 hr after dosing with the triterpene the enzyme activities were further decreased. The reduction in the activities of the bile canalicular enzymes preceded retention of bilirubin as estimated by serum bilirubin levels. It is concluded that reduced lantadene A may cause hepatotoxicity through a toxic metabolite and that injury to bile canaliculi is an early lesion in the development of cholestasis.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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