Interactions between nonsteroidal anti-inflammatory drugs and biological membranes—III: Effect of nonsteroidal anti-inflammatory drugs on bound mitochondrial bromothymol blue and possible intramitochondrial pH variations induced by these drugs

Abstract

Ten nonsteroidal anti-inflammatory drugs (NSAID), which are known to affect mitochondrial membrane properties, were examined for their ability to induce variations of absorbance in isolated mitochondria preloaded with bromothymol blue (BTB). By studying optical density curves at 618 nm and at the isosbestic point of BTB, an index, ICC BTB, was defined, which reflects BTB color changes. The NSAID, and some alcohols related to them, increase this index. This change is related to the drug concentration as well as to the ionic composition of the incubation medium. Such BTB color variations in mitochondria could be due to alkalinization of the matrix space which occurs simultaneously with reorientation of the BTB molecules at their mitochondrial location. At concentrations which affect many other functions in various biological membranes, NSAID may alter the mitochondrial membrane permeability and promote the penetration of alkali cations into the mitochondria. The ionic movements cause the interior of the mitochondria to become alkaline, through a parallel excretion of protons or a concomitant uptake of hydroxyl ions, or both, while a simultaneous water influx causes mitochondrial swelling.