Modulatory Effects of L-Arginine on Methylxanthine-Induced Cardiotoxicity in Rats: A Differential Role for Nitric Oxide (NO)

Author Info

Md Shamsuzzaman Jagdish C. Joshi Kavita Gulati Arunabha Ray

Corresponding Author

Arunabha Ray
Department of Pharmacology, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India

A B S T R A C T

Methylxanthines are potent bronchodilators used in obstructive airway disease like COPD and bronchial asthma, but the narrow therapeutic index and resultant adverse effect profile have restricted their use. Novel beneficial effects and modes of action are now being proposed for these pharmacoeconomically viable agents. Cardiotoxicity is a prominent adverse effect of methylxanthone and thus we investigated possible mechanisms for such toxicity with an aim to devise ameliorative strategies for counteracting such undesirable effects. In view of the cardioprotective role of nitric oxide (NO) and NO mimetics, the present study investigated the possible modulatory role of L-arginine, a NO precursor, in theophylline induced cardiotoxicity in rats, with a view to exploring strategies for facilitating the safe use of this drug. The methylxanthine, aminophylline induced cardiotoxic effects like increased heart rat, raised mean BP, inverted T-waves and prolonged QTc interval (in ECG). These were accompanied by increased levels of cardiac biomarkers like Troponin-I, CPK-MB, and ADMA. Oxidative stress markers like MDA were elevated whereas, antioxidant defence markers like GSH and SOD were suppressed. Co-administration of L-arginine (with aminophylline) had dose-related effects on cardiac function (heart rate, mean BP, ECG changes) and cardiospecific biomarkers (TnI, CPK-MB, ADMA) - the lower dose being protective whereas the higher dose potentiating some of the cardiac effects and cardiospecific/oxidative stress biomarker levels. The results indicate a biphasic involvement of NO in the cardiotoxic effect of theophylline and suggests possible interactions of NO with reactive oxygen species during such modulations of cardiotoxicity.

Article Info

Article Type

Research Article

Publication history

Received: Tue 17, Aug 2021
Accepted: Mon 30, Aug 2021
Published: Mon 13, Sep 2021

Copyright

© 2023 Arunabha Ray. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.JICOA.2021.03.09