IPSIndian Journal of Pharmacology
Home  IPS  Feedback Subscribe Top cited articles Login 
Users Online : 1477 
Small font sizeDefault font sizeIncrease font size
Navigate Here
 »   Next article
 »   Previous article
 »   Table of Contents

Resource Links
 »   Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »   Citation Manager
 »   Access Statistics
 »   Reader Comments
 »   Email Alert *
 »   Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed1420    
    Printed90    
    Emailed0    
    PDF Downloaded129    
    Comments [Add]    

Recommend this journal

 

 RESEARCH PAPER
Year : 1999  |  Volume : 31  |  Issue : 4  |  Page : 299-305

Effect of coadministration of antituberculous drugs on the hepatic drug metabolizing enzymes and oxidative stress in the mouse



Correspondence Address:
K V Ramana


Login to access the Email id

Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions

Objective: To investigate whether the coadministration of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) was more potent than RMP alone in the induction of drug metabolizing enzymes and the causation of oxidative stress in the mouse. Methods: Male mice were administered intraperitoneally 40 mg RMP or simultaneously 40, 40 and 80 mg INH, RMP and PZA per Kg body weight for 3 days. The livers were homogenized in potassium phosphate buffer containing potassium chloride. Microsomes and 100,000 x g supernatant were prepared by differential centrifugation. Assays of cytochrome P450, NADPH cytochrome c reductase, erythromycin N-demethylase and lipid peroxidation were performed in the microsomes. Assays of glutathione reductase, glutathione peroxidase and catalase were performed in 100,000 x g supernatant. Glutathione was assayed in supernatant from 5% TCA homogenate of the liver specimen. Results: Coadministration of INH, RMP and PZA increased the hepatic microsomal cytochrome P450, lipid peroxidation, the activities of NADPH cytochrome c oxidoreductase, erythromycin N-demethylase, Se-independent glutathione peroxidase and intensified 53.5 and 56 kDa polypeptides in the mouse. RMP increased all these parameters except the activity of selenium independent glutathione peroxidase. However, changes caused in the lipid peroxidation and the activity of erythromycin N-demethylase by coadministration of INH, RMP and PZA were more dramatic as compared to RMP. Both treatments did not alter the hepatic glutathione and activities of glutathione reductase, Se-dependent glutathione peroxidase, superoxide dismutase but decreased the activity of catalase in the mouse. Conclusion: Coadministration of INH, RMP and PZA was more potent in the induction of the hepatic microsomal erythromycin N demethylase and causation of oxidative stress in the mouse as compared to RMP administration alone.






[PDF]*


        
Print this article     Email this article

Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer
Online since 20th July '04
Published by Wolters Kluwer - Medknow