Suramin inhibits respiration and induces membrane permeability transition in isolated rat liver mitochondria

• Published in: Toxicology (Amsterdam) 2001-12, Vol.169 (1), p.17-23
• Main Authors: Bernardes, Celene F, Fagian, Marcia M, Meyer-Fernandes, José R, Castilho, Roger F, Vercesi, Anibal E
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Animals; Biological and medical sciences; Ca 2; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - antagonists & inhibitors; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone - pharmacology; Cell Membrane Permeability - drug effects; Cell Respiration - drug effects; Chelating Agents - pharmacology; Cyclosporine - pharmacology; Drug Interactions; Drug toxicity and drugs side effects treatment; Egtazic Acid - pharmacology; Enzyme Inhibitors - pharmacology; Ethylmaleimide - pharmacology; Intracellular Membranes - drug effects; Intracellular Membranes - physiology; Isolated rat liver mitochondria; Magnesium - pharmacology; Medical sciences; Membrane Potentials - drug effects; Miscellaneous (drug allergy, mutagens, teratogens...); Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial membrane permeability transition; Mitochondrial Swelling - drug effects; Oxygen Consumption - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Sulfhydryl Reagents - pharmacology; Suramin; Suramin - toxicity; Thiol oxidation; Trypanocidal Agents - toxicity
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(01)00477-2

Suramin, a polysulfonated naphthylamine, caused a dose dependent inhibition of carbonyl cyanide p-(tri-fluoromethoxy)phenylhydrazone-stimulated respiration supported either by succinate or a cocktail of αketoglutarate, malate and isocitrate in isolated rat liver mitochondria. The half-maximum effect was obtained at 40 and 140 μM suramin for NADH- or FADH 2-linked substrates, respectively. The respiration supported by N, N,, N′ N′-tetramethyl- p-phenylenediamine oxidation was unaffected by suramin (⩽500 μM). The latter respiratory substrate was used in the studies at examining the effects of suramin on the permeability properties of the inner mitochondrial membrane. These experiments provided evidence that suramin causes Ca 2+-dependent mitochondrial swelling sensitive to the mitochondrial permeability transition (MPT) inhibitors cyclosporin A, ADP and Mg 2+. In addition, suramin decreased the content of reduced mitochondrial membrane protein thiols suggesting that thiol oxidation is the mechanism underlying suramin-induced MPT.