INFLUENCE OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON CALCIUM EFFLUX INISOLATED RAT RENAL-CORTEX MITOCHONDRIA AND ASPECTS OF THE MECHANISMS INVOLVED

In the present study we investigated the influence of several nonstero idal anti-inflammatory drugs on calcium efflux in isolated rat renal c ortex mitochondria in order to assess their potential to disrupt cell calcium homeostasis, as well as aspects of the mechanisms associated w ith oxidation of mitochondrial pyridine nucleotides (NAD(P)H) and with inhibition of the process by cyclosporin A (CsA). Calcium efflux was estimated with arsenate III as an indicator and the redox state of NAD (P)H was monitored fluorimetrically at the 366/450 nm excitation/emiss ion wavelength pair. Dipyrone, paracetamol and ibuprofen did not induc e calcium efflux even at 1 mM, piroxicam and salicylate were poor indu cers, while diclofenac sodium and mefenamic acid were potent inducers releasing calcium even at 20 mu M and 10 mu M, respectively. In the pr esence of 10 mu M calcium, CsA had no appreciable effect while in the presence of 30 mu M calcium it delayed calcium efflux. Oxidation of mi tochondrial NAD(P)H, concomitant with calcium efflux and inhibited by CsA, was observed only in the presence of 30 mu M calcium. The results suggest that diclofenac sodium and mefenamic acid induce calcium effl ux in mitochondria through both a mechanism intrinsic to the mitochond rial membrane permeability transition and a mechanism including the el ectroneutral Ca2+/nH(+) porter. (C) 1998 Elsevier Science Ltd. All rig hts reserved.