Protection by pentoxifylline of malathion-induced toxic stress and mitochondrial damage in rat brain

Abstract

<jats:p> Objective: The objective of this study was to investigate the possible protective effects of pentoxifylline as a phosphodiesterase-5 inhibitor on malathion-induced oxidative damage to rat brain mitochondria. Methods: Rats received malathion (200 mg/kg/day) and pentoxifylline (PTX, 50 mg/kg/day) in combination or alone. Alpha-tocopherol (AT, 15 mg/kg/day) was used as a positive standard. After 1 week of treatment, blood, whole brain tissue, and brain mitochondria were isolated. The activity of enzymatic scavengers such as glutathione peroxidase (GPx), catalase (CAT), copper-zinc superoxide dismutase (Cu/ZnSOD), and manganese superoxide dismutase (MnSOD) were measured. The extents of cellular lipid peroxidation (LPO), nitrotyrosine (NOx), and the ratio of reduced versus oxidized glutathione (GSH/GSSG) were determined. The protein expression of MnSOD was determined in brain mitochondria. Results: Malathion stimulated activities of CAT, Cu/ZnSOD, GPx, and increased LPO and NOx, and decreased GSH/GSSG in whole brain homogenate. The changes in CAT, LPO, GPx, and GSH/GSSG were restored by PTX and AT. In plasma samples, malathion increased CAT, Cu/ZnSOD, and GPx activities, increased LPO, and decreased GSH/GSSG, while PTX and AT attenuated malathion-induced changes in GPx, Cu/ZnSOD, LPO, and GSH/GSSG. In brain mitochondria, malathion enhanced LPO, NOx, CAT, GPx, and MnSOD and decreased GSH/GSSG as compared to controls, whereas PTX and AT restored malathion-induced changes in GSH/GSSG, NOx, GPx, and CAT. Malathion noticeably enhanced expression of MnSOD protein as compared to controls. Malathion decreased viability of mitochondria that was recovered by AT. It is concluded that oxidative damage is at least in part the mechanism of toxicity of malathion in the mitochondria that can be recovered by PTX comparable to AT. </jats:p>

3-nitrotyrosine levels in dichlorvos-induced neurotoxicity

“…Our study confirms increased brain nitration markers from studies with other OP pesticides such as malathion (15) and chlorpyrifos (16). In contrast, Kose et al (17) concluded that acute dichlorvos administration did not cause marked oxidative stress in rat heart and that oxidative stress probably did not play a major role in dichlorvos-induced poisoning.…”

Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

“…The choice of antioxidants is wide, but several have been evidenced as potent against OP toxicity, including selenium (167), N-acetylcysteine (NAC), pentoxifylline (PTX), and alpha-tocopherol. NAC has been reported to significantly decrease lipid peroxidation, hospital time, and mortality in poisoned patients (168), whereas PTX and alpha-tocopherol reverse OP-induced effects on glutathione, nitrotyrosine, CAT, and GPx (65,169,170). Recently, a new generation of possible antidotes to OP poisoning has raised interests, the so called OP hydrolases produced by bacteria, but research has not yet reached clinical stage (171).…”

Effects of Vitamins E and C on Freezed-Thawed Immature Mice Testis

“…In mild or moderate oxidative stress occurrence, tissues often counteract its effect, but in the case of severe oxidative stress, the cells injury and may lead to cell death. In necrosis and apoptosis, free radicals are the major cause of cell death and in fact anti-apoptotic genes code a number of free radical neutralizers [19]. So there is essential need for strategies to reduce damages and substance cytotoxicity in solutions, for example many researchers believe that to combat the harmful effects of cryopectans and free radicals and oxidative stress, freezing-thawing, environments must be optimized [17] and they believe that cell type and the kinds of solutions effectively affect on the quality of freezed-thawed cell [20].…”