Elsevier

Biochemical Pharmacology

Volume 35, Issue 6, 15 March 1986, Pages 979-984
Biochemical Pharmacology

Renal mitochondrial integrity during continuous gentamicin treatment

https://doi.org/10.1016/0006-2952(86)90086-9Get rights and content

Abstract

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.

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      Undoubtedly, the presence of aminoglycosides in the astrocytes disturbs the mitochondrial microenvironment even more. It is known that gentamicin inhibits mitochondrial energy-linked functions in the kidney (Mela-Riker et al., 1986), enhances the permeability of monovalent cations in kidney cortical mitochondria (Weinberg et al., 1980), and enhances calcium entry in hair cells (Dehne et al., 2002; Tan et al., 2001). The relocation of highly reactive ions, such as calcium, inside cells could induce changes, including cytoskeleton deformation, that lead to mitochondrial deformation.

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    Leena M. Mela-Riker, M. D., Department of Surgery, Oregon Health Sciences University, 3181 S. W. Sam Jackson Park Road, Portland, OR 97201.

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