A Study of Potential Toxic Effects After Repeated 10-Week Administration of a New Iron Chelator – Salicylaldehyde Isonicotinoyl Hydrazone (SIH) to Rabbits

Abstract

Salicylaldehyde Isonicotinoyl Hydrazone (SIH)--a Pyridoxal Isonicotinoyl Hydrazone (PIH) analogue--is an effective iron chelator with antioxidant and antimalarial effects, as documented in numerous in vitro studies. However, no toxicological data obtained from in vivo studies have been made available yet. In this study, the potential toxic effects of repeated administration of SIH (50 mg/kg, once weekly, 10 weeks, i.p.), partially dissolved in a 10% Cremophor solution, on various biochemical, haematological, and cardiovascular parameters and on morphology of selected tissues were investigated in rabbits. The obtained values were compared with data from the control (saline, 1 ml/kg, i.v.) and the Cremophor (10% Cremophor solution, 2 ml/kg, i.p.) groups. In this study, SIH did not induced marked signs of toxicity: No premature deaths occurred, the body weight increase was comparable with the control and Cremophor groups. Only few and mild changes in some biochemical and haematological parameters could be determined, most of them were noticed also in the control or Cremophor groups. The morphological changes in the kidney were mild and did not manifest in the biochemical examination. The cardiac function was also not affected markedly--the values of left ventricular ejection fraction and systolic time interval did not differ from the values of control group. Only an increased left ventricular contractility (dP/dtmax) was noticed in the SIH group at the end of the experiment as compared to the controls (13,354+/-1191 vs. 9339+/-647 mmHg/s, resp.). These results seem to be promising from the standpoint of possible clinical use of SIH.