Low doses of heavy metals disrupt normal structure and function of rat platelets.
Aggregation, an important property of platelets, plays a key role in the coagulation of blood and is potentiated by ADP and adrenaline, whereas cAMP acts as a strong inhibitor. Because of the rise in the heavy metal load in the environment, more studies are necessary to look at its subtle effects in the animal system, wherein platelet structure and function can be targeted. We carried out structural analyses under phase contrast and scanning electronmicroscopy of the platelets prepared from 1/10 LD50 metal-treated rats. After mercury (Hg) and arsenic (As) treatment, the cell margins appeared irregular and wavy, with small pseudopodia-like protrusions from the surface. Cadmium (Cd) treatment caused loss of the general spindle shape, and the platelets assumed a round spongy appearance. All metal treatments effected enhanced collagen-induced aggregation and inhibited ADP- and arachidonic acid-induced aggregation, whereas epinephrine accelerated aggregation in Hg and Cd treatment but inhibited aggregation in As treatment. Cd proved a potent inhibitor of phosphodiesterase, increasing the cAMP level in in vitro treatments at equimolar (5, 10, and 20 pmoles) concentrations. The rate of aggregation was enhanced with all the agonists used in in vitro Hg and As treatments, with concomitant reduction in cAMP, while Cd inhibited platelet aggregation. Thus, we can conclude that cytosolic cAMP, which is decreased by the metal-induced inhibition of phosphodiesterase, is a regulator molecule in platelet aggregation. Furthermore, it is also abundantly clear that equimolar doses of metals are not always equitoxic. Therefore, the action of each xenobiotic is not only due to the concentration used but also to the type of xenobiotic depending on its unique mechanism of action.
Kumar
S V
SV
Department of Zoology, Visva Bharati University, West Bengal, India.
Bose
R
R
Bhattacharya
S
S
D000818:Animals; D001151:Arsenic / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D002104:Cadmium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D008297:Male; D008628:Mercury / Q000494:pharmacology; D019216:Metals, Heavy / Q000008:administration & dosage / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D019216:Metals, Heavy; D002104:Cadmium; D000242:Cyclic AMP; D008628:Mercury; D001151:Arsenic