Table of Contents
Metal-Based Drugs
Volume 6 (1999), Issue 2, Pages 87-93

Effects of Long-Term Administration of Lithium and Hydrochlorothiazide in Rats

Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy, 13 Emil Isac, Cluj-Napoca 3400, Romania

Received 18 January 1999; Accepted 8 February 1999

Copyright © 1999 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The biochemical and histological changes following 60 days administration of daily doses equivalent to 1/20 LD50 of lithium lactate and hydrochlorothiazide, as such and in association, were studied in male Wistar rats. No mortality or overt signs of toxicity were observed during the experiment and the serum activities of transaminases, alkaline phosphatase and cholinesterase were not significantly modified compared to controls. The histopathological examination of all the investigated organs: kidney, liver, brain and spleen, revealed significant lesions which were time-dependant and more pronounced in the association group. Although the changes were mostly inflammatory and conqestive, it was proved that the concomitant administration of lithium and hydrochlorothiazid is potentially dangerous, increasing lithium’s nephrotoxicity and the thiazide diuretic's hepatotoxicity.