Renal mitochondrial integrity during continuous gentamicin treatment.
Rats were given gentamicin over a period of 21 days. At 5, 10, 14 and 21 days renal cortical mitochondria were isolated, and respiratory and Ca2+ transport functions and cytochrome concentrations were determined. The mitochondrial data were correlated with indicators of deteriorating renal function and tissue gentamicin accumulation. During the first 10 days of chronic gentamicin treatment, mitochondrial cytochrome oxidase and cytochrome c concentrations declined significantly. This decline was followed by a partial spontaneous recovery by days 14 and 21. Cytochrome b concentration was not significantly different from normal. Parallel with the cytochrome concentration changes, State 3 respiratory activities with all substrates studied and the rates of Ca2+ accumulation declined during the first 10 days and recovered spontaneously thereafter. It is concluded that chronic gentamicin treatment leading to renal failure inhibits mitochondrial energy-linked functions, which inhibition is induced by rate-limiting synthesis of those mitochondrial respiratory chain enzymes coded outside the mitochondrion.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003573:Cytochrome b Group / Q000032:analysis; D003574:Cytochrome c Group / Q000032:analysis; D003576:Electron Transport Complex IV / Q000032:analysis; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D003573:Cytochrome b Group; D003574:Cytochrome c Group; D005839:Gentamicins; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D002118:Calcium