| 20194575 |
Ranjbar A, Ghahremani MH, Sharifzadeh M, Golestani A, Ghazi-Khansari M, Baeeri M, Abdollahi M: Protection by pentoxifylline of malathion-induced toxic stress and mitochondrial damage in rat brain. Hum Exp Toxicol. 2010 Mar 1.
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. |
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