Review: Circulatory disorders induced by ochratoxin A

Abstract

Ochratoxin A (OA) or (OTA) is a mycotoxin produced by certain Penecillium (mainly P. verrucosum) and Aspergillus (mainly A. occracies) species of storage fungi. This toxin is a secondary fungal metabolites which has been detected in a variety of animal chows, human food and in up to 80% of human blood samples of several Western countries. Its main target is the kidney which is the causing agent of Danish porcine nephropathy and increases the incidence of renal carcinomas and adenomas in rats. OA produces many other adverse effects on animals and human since it is known as teratogen, mutagen and immunosuppressive agent. Several mechanisms of OA toxicity have been proposed by several investigators. The present manuscript introduces the circulatory disturbances as well as several cases of cardiac disorders which have been recorded following the acute administration of ochratoxin A to adult rats. A dose-dependent relationship of ochratoxin A has been established. OA decreased the heart rate of adult rats after 30 min from the IP injection. Hypotension as well as a significant change in mean arterial blood pressure and decrease in the conduction time of the heart cycle were established also following ochratoxicosis. Other electrophysiological changes included significant inotropic effect and increase of ventricle repolarization voltage have been reported after OA treatment. The abnormalities of heart function include abnormal sinus rhythms, arising of ectopic beats and atrioventricular block. A drop and change of pulse pressure of the arterial blood pressure have been recorded simultaneously with multiple cases of arterial premature contractions (APC) and sinus arrhythmia (SA). The cardiotoxic mechanism of OA has been established by both in vivo and in vitro study on the rat and frog hearts. Sympathetic and parasympathetic antagonisms as well as calcium channels blocker have been employed. It is suggested that OA exerted its cardiotoxic effects mainly through increased influx of extracellular calcium ions, which postulates a possible direct effect of OA on the myocardium cell membranes integrity. Morover, OA can exert a parasympathetic stimulation to the heart in both the in vivo and in-vitro study. Ochratoxin A seriously affects the circulating blood and the circulating body fluid which are currently defined as the internal environment that facilitate the metabolic processes and homeostasis. Microcytic hypochromic anemia, reduced mean corpuscular volume and decrease of other haematological measurements were reported in different species of animals toxificated by OA. Ochratoxin A not only produced amelioration in the pH of intersititial fluid which provides the exchange medium for substances moving between cells and capillary plasma, but also within the cell membrane on the intracellular fluid, which serve as the liquid environment for chemical reactions necessary to cellular survival.


KEY WORDS: ECG, blood pressure, Autonomic nervous system, Body fluids, calcium channels, rat, frog.


Egyptian Journal of Biology Vol.4 2002: 147-156