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

• Published in: Food and chemical toxicology Vol. 136; p. 110971
• Main Authors: Klinova, Svetlana V., Minigalieva, Ilzira A., Privalova, Larisa I., Valamina, Irene E., Makeyev, Oleg H., Shuman, Eugene A., Korotkov, Artem A., Panov, Vladimir G., Sutunkova, Marina P., Ryabova, Julia V., Bushueva, Tatiana V., Shtin, Tatiana N., Gurvich, Vladimir B., Katsnelson, Boris A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2020
• Subjects: Animals; Animals, Outbred Strains; Bio-protection; Cadmium; Cadmium - blood; Cadmium - toxicity; Cadmium Chloride - administration & dosage; Cadmium Chloride - toxicity; Cardio-vascular toxicity; Combined toxic action; DNA Fragmentation - drug effects; Drug Synergism; Echocardiography - drug effects; Genotoxicity; Heart - drug effects; Hemodynamics - drug effects; Injections, Intraperitoneal; Kidney - drug effects; Kidney - pathology; Lead; Lead - blood; Lead - toxicity; Male; Mutagens - toxicity; Myocardium - pathology; Organometallic Compounds - administration & dosage; Organometallic Compounds - toxicity; Rats; Subchronic intoxication; Toxicity Tests, Subchronic; Cadmium; Combined toxic action; Subchronic intoxication; Bio-protection; Genotoxicity; Lead; Cardio-vascular toxicity
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2019.110971

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. •Rats repeatedly injected IP with Pb acetate and/or Cd chloride developed outcomes either common to Cd and Pb or Pb-specific.•For the first time, hemodynamic and electrocardiographic effects of this toxic combination was studied.•Causal association of many features with Cd or Pb impact was confirmed by their correlation with blood metal level.•For one and the same toxic combination, the type of combined toxicity can vary from synergistic to contra-directional.•Many toxic effects of the combination, genotoxicity included, were attenuated by background administration of bioprotectors.