Mercury compounds: lipophilicity and toxic effects on isolated myocardial tissue.
Lipophilicity is suggested to modulate the diffusion and the cytotoxic effects of mercury compounds. To investigate this, the positive inotropic effect of four Hg compounds (HgCl2, CH3HgCl, chlormerodrin, bromomercurihydroxypropane) was studied in catecholamine-depleted isolated heart muscle preparations. The rate of development of the positive effect was inversely correlated to the concentration in the case of HgCl2 and chlormerodrin, i.e. the product of concentration (c) and time to half-maximal effect (t50) remained constant. This was in accordance with the assumption of a permeation-controlled rate of action, as was shown earlier for p-chloromercuriphenyl-sulfonic acid. In addition, the c X t50 values of the individual mercurials decreased hyperbolically with the increase in lipophilicity as measured by the octanol/water partition. The results support the view that the toxicity of mercurials increases with their lipid solubility. In conjunction with the previously reported negative inotropic effect of Hg compounds, a model is proposed allocating thiol groups responsible for the negative inotropic action to lipid compartments within the cell membrane, while SH groups conveying the increase in contraction force are thought to be situated at the internal surface of the sarcolemma.
Halbach
S
S
Gesellschaft für Strahlen- und Umweltforschung, Institut für Toxikologie, Neuherberg, Federal Republic of Germany.
D000818:Animals; D002316:Cardiotonic Agents; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002717:Chlormerodrin / Q000633:toxicity*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects; D009941:Organomercury Compounds / Q000633:toxicity*
D002316:Cardiotonic Agents; D008767:Methylmercury Compounds; D009941:Organomercury Compounds; C000316:1-bromomercuri-2-hydroxypropane; D008627:Mercuric Chloride; D002717:Chlormerodrin; C004925:methylmercuric chloride