Comparative effects of the herbicide dinitro-o-cresol on mitochondrial bioenergetics

Abstract

The herbicide dinitro‐o‐cresol (DNOC) was evaluated for its effects on bioenergetic activities of potato tuber mitochondria to elucidate its mechanism of action and to compare its toxicological properties with those of the chemically related uncoupler dinitrophenol (DNP). DNOC acts as a typical uncoupler, similarly to the classical uncouplers DNP and carbonylcyanide p‐trifluoromethoxyphenyl‐hydrazone (FCCP). Low concentrations of DNOC (<100 μM) maximally stimulate succinate‐supported respiration of plant mitochondria, with simultaneous collapse of trans‐membrane electrical potential, more efficiently than DNP. The herbicide makes the plant mitochondrial membrane more permeable to protons, acting as a protonophore even in non‐energized mitochondria. High concentrations of DNOC (>100 μM) act also more efficiently than DNP simultaneously as a protonophore and inhibitor of respiration, especially when respiration is supported by substrates that are transported to the matrix. The efficiency of DNOC is decreased with increase of mitochondrial protein, BSA and exogenous orthophosphate. Although similar effects were observed for animal and plant mitochondria, rat‐liver mitochondrial respiration was more sensitive to DNOC than plant mitochondria. Furthermore, in the presence of DNOC, liver mitochondria exhibited a higher state 3 respiratory coupling level than potato tuber mitochondria, as a result of a considerable stimulation (60%) of state 3 respiration. In conclusion, DNOC is a more potent mitochondrial uncoupler and respiratory chain inhibitor than DNP, although their chemical structures are very similar. Apparently, the additional methyl group of DNOC increases its efficiency as an uncoupler and as an inhibitor, as compared to DNP. Plant mitochondria were shown to be as useful as animal mitochondria in evaluating the toxicity of these xenobiotics. © 1998 Society of Chemical Industry.

Hepatotoxicity of dinitro-O-cresol in rats (Rattus norvegicus)

“…It was explained that in their electron microscopic investigations, swelling of mitochondria and breaking up of the mitochondrial cristae of hepatocytes in diazinon-treated groups were observed. In another study, Vicente et al (1998) showed that liver mitochondria of rats are much more sensitive than the mitochondria of plants. All these studies show that DNOC affects enzyme activityes.…”

A non-invasive observation parameter to complement sediment bioassays using Myriophyllum aquaticum

“…Thereby, DNOC mimics the physiological effects of decouplers by stimulating the respiration of animal and higher plant mitochondria (Vicente et al 1998). Because of this mechanism, inhibitory effects on Y(II) as well as on growth of exposed M. aquaticum whorls were expected as subsequent effects.…”

Dinitro-o-cresol induces apoptosis-like cell death but not alternative oxidase expression in soybean cells

“…DNOC toxicity may result from the uncoupling effect on mitochondrial oxidative phosphorylation as previuously proposed (Castilho et al, 1997;Vicente et al, 1998), and was evaluated by comparing its influence at different concentrations in soybean cell culture growth.…”

“…Previous studies using isolated mitochondria have indicated that DNOC mimics the physiological effects of uncouplers by dissipating the transmembrane electrical potential (Dc) and stimulating respiration (Vicente et al, 1998). Accordingly, DNOC at low concentrations would act as a typical uncoupler; but higher concentrations of DNOC would simultaneously uncouple and inhibit respiration.…”