Changes in the Cardiotoxic Effects of Lead Intoxication in Rats Induced by Muscular Exercise.

Exposure to lead is associated with an increased risk of cardiovascular diseases. Outbred white male rats were injected with lead acetate intraperitoneally three times a week and/or were forced to run at a speed of 25 m/min for 10 min 5 days a week. We performed noninvasive recording of arterial pressure, electrocardiogram and breathing parameters, and assessed some biochemical characteristics. Electrophoresis in polyacrylamide gel was used to determine the ratio of myosin heavy chains. An in vitro motility assay was employed to measure the sliding velocity of regulated thin filaments on myosin. Isolated multicellular preparations of the right ventricle myocardium were used to study contractility in isometric and physiological modes of contraction. Exercise under lead intoxication normalized the level of calcium and activity of the angiotensin-converting enzyme in the blood serum, normalized the isoelectric line voltage and T-wave amplitude on the electrocardiogram, increased the level of creatine kinase-MB and reduced the inspiratory rate. Additionally, the maximum sliding velocity and the myosin heavy chain ratio were partly normalized. The effect of exercise under lead intoxication on myocardial contractility was found to be variable. In toto, muscular loading was found to attenuate the effects of lead intoxication, as judged by the indicators of the cardiovascular system.

Further verification of some postulates of the combined toxicity theory: New animal experimental data on separate and joint adverse effects of lead and cadmium.

Outbred male rats were repeatedly injected intraperitoneally two-level sub-lethal doses of lead acetate and/or cadmium chloride solutions 3 times a week during 6 weeks. The animals developed explicit, even if moderate, subchronic intoxication characterized by a large number of indices, both common to both metals (including increased DNA fragmentation coefficient) and lead-specific. Special attention was paid to hemodynamic and electrocardiographic effects. The combined action of lead and cadmium was modeled with the help of the Response Surface Methodology to obtain additional support for the previously substantiated postulates of combined toxicity's typological ambiguity. This is dependent on which particular effect comes under consideration, on its level, and on the acting dose ratio. For one and the same toxic combination, the type of combined toxic action can vary from synergistic to contra-directional. In particular, the actions of lead and cadmium on blood pressure were found to be opposite in direction. Furthermore, it is shown once again that the systemic toxic effects of a metal combination, its in vivo genotoxicity included, can be more or less attenuated by background administration of a theoretically justified composition of biologically active agents.