Effects of in vivo treatment of rats with trimethyltin chloride on respiratory properties of rat liver mitochondria.
Liver mitochondria isolated from rats treated in vivo with trimethyltin chloride show stimulation of respiration using glutamate/malate as substrate, and a transient inhibition on rates of respiration using palmitoyl-L-carnitine as substrate. This phenomenon was observed with both ADP- and FCCP-stimulated respiration. In contrast, rates of respiration by liver mitochondria isolated from rats treated in vivo with trimethyltin chloride, following prior treatment with clofibrate, were inhibited when glutamate/malate was respiratory substrates. With palmitoyl-L-carnitine no effect of trimethyltin chloride was observed. In vitro treatment of rat liver mitochondria, or of rat liver homogenates, led to the expected, powerful inhibition of respiration. The synthesis of ATP by liver mitochondria isolated from rats treated in vivo with trimethyltin chloride was not inhibited compared to mitochondria isolated from control rats. Similarly, ATP synthesis by mitochondria isolated from rats treated with clofibrate, before treatment with trimethyltin chloride, was not inhibited. We, therefore, conclude that the powerful inhibitory effects of trimethyltin found in vitro, is not expressed in vivo during the first 36 hr following administration. In vivo treatment of rats with trimethyltin chloride caused a marked increase in hepatic levels of taurine and glycine, while levels of glutathione and glutamine were diminished. This is consistent with an enhanced oxidative stress in the liver. Our findings lead to the conclusion that increased oxidative stress, rather than inhibition of the mitochondrial ATPase, is a likely major cause of the in vivo toxic effects due to trimethyltin chloride.
Skarning
Cecilie Resen-Fellie
CR
Institute of Oral Biology, University of Oslo, Box 1052, Blindern, Norway.
Varhaug
Ludvig Nord
LN
Fonnum
Frode
F
Osmundsen
Harald
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002994:Clofibrate / Q000494:pharmacology; D004347:Drug Interactions; D005973:Glutamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010172:Palmitoylcarnitine / Q000378:metabolism; D020675:Peroxisomes / Q000187:drug effects; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D014001:Tin / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000494:pharmacology*
D000596:Amino Acids; D000960:Hypolipidemic Agents; D014298:Trimethyltin Compounds; D005973:Glutamine; D010172:Palmitoylcarnitine; D014001:Tin; D000255:Adenosine Triphosphate; C040533:trimethyltin chloride; D005978:Glutathione; D002994:Clofibrate