Protective Effects of Edaravone against Methamphetamine-Induced cardiotoxicity

Abstract

Methamphetamine (METH) is widely abused in worldwide. METH use could damage the dopaminergic system and induce cardiotoxicity via oxidative stress and mitochondrial dysfunction. Edaravone, a sedative-hypnotic agent, is known for it's antioxidant properties. In this study we used edaravone for attenuating of METH-induced cardiotoxicity in rats. The groups (six rats in each group) were as follows: control, METH (5 mg/kg IP) and edaravone (5, 10 and 20 mg/kg, IP) was administered 30 min before METH. After 24 hours, animals were killed, heart tissue was separated and mitochondrial fraction was isolated and oxidative stress markers were measured. Edaravone significantly (p<0.05) protected the heart against lipid peroxidation by inhibition of reactive oxygen species (ROS) formation. Edaravone also significantly (p<0.05) increased the levels of heart glutathione (GSH). METH administration significantly (p<0.05) disrupted mitochondrial function that edaravone pre-treatment significantly (p<0.05) inhibited METHinduced mitochondrial dysfunction. Protein carbonyl level also increased after METH exposure, but was significantly (p<0.05) decreased with edaravone pre-treatment. These results suggested that edaravone is able to inhibition of METH-induced oxidative stress and mitochondrial dysfunction and subsequently METH-induced cardiotoxicity. Therefore, the effectiveness of this antioxidant should be evaluated for the treatment of METH toxicity and cardio degenerative disease.

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“… 20 Similarly, ED decreased ROS and MDA and increased the activity of antioxidant enzymes in the heart of valproic acid- 43 and methamphetamine-induced rats. 42 These studies along with the findings of this study demonstrate the potent antioxidant activities of both AV and ED.…”

“…For instance, AV showed protective effects against cisplatin cardiotoxicity, 40 isoproterenol-induced cardiac hypertrophy 41 and diabetic cardiomyopathy. 20 ED has also shown protective effects in animal models of methamphetamine-, 42 valproic acid- 43 and doxorubicin-induced cardiotoxicity. 44 In these studies, the cardioprotective effects of AV and ED were attributed mainly to their ability to attenuate oxidative stress.…”

“…For instance, AV showed protective effects against cisplatin cardiotoxicity, 40 isoproterenolinduced cardiac hypertrophy 41 and diabetic cardiomyopathy. 20 ED has also shown protective effects in animal models of methamphetamine-, 42 valproic acid-43…”

“…The ability of AV and ED to attenuate oxidative stress in different models of cardiac injury has been previously reported. 20,[40][41][42][43][44] In cisplatin-intoxicated rats, oral supplementation of 600 mg/L AV for 5 days decreased cardiac LPO and increased GSH. 40 AV increased cardiac GSH in isoproterenol-induced rats 41 and serum SOD and catalase in diabetic rats.…”

Effects of tramadol administration on male reproductive toxicity in Wistar rats The role of oxidative stress, mitochondrial dysfunction, apoptosis-related gene expression, and nuclear factor kappa B signalling

“…Briefl y, determination of the supernatant absorbance at 532 nm on the ELISA reader (Tecan, Rainbow Thermo, Austria) is the method used to evaluate the amount of MDA formation. The standard is tetramethoxypropane and fi ndings were expressed as micromolar (μM)/mg protein (26).…”