Effects of Molsidomine against Doxorubicin-Induced Cardiotoxicity in Rats

Abstract

Purpose: To explore the protective and curative effects of molsidomine (MOL) on doxorubicin (DOX)-induced cardiac damage in the in vivo rat heart. Methods: Forty rats were randomized into five groups (n = 8): (1) the control group; (2) the MOL group (10 mg/kg for 21 days); (3) the DOX group (a single dose of 20 mg/kg); (4) the DOX + MOL group (3 days after the single dose of DOX, 10 mg/kg MOL continued for 21 days), and (5) the MOL + DOX group (24 h after a 21-day regimen of 10 mg/kg MOL, a single dose of DOX). The rats were monitored for mean arterial blood pressure, heart rate, O₂ saturation, and electrocardiography. Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and nitric oxide (NO) were determined. Results: Blood pressure and O₂ saturation values indicated a significant decrease in the DOX group compared with the control group. T negativity was observed in 4 of 8 rats in the DOX group, in 1 of 8 rats in the DOX + MOL group, and in 4 of 8 rats in the MOL + DOX group. MDA levels were significantly higher in the DOX group. SOD, GSH, and NO levels were significantly lower in the DOX group compared with the other groups. There was no statistically significant difference in the CAT levels in any of the study groups compared with controls. DOX treatment induced morphological alterations, such as disorganization of cardiomyocytes, loss of myofibrils, and cytoplasmic vacuolization in the heart. On the other hand, histological damage was significantly reduced in the DOX + MOL and MOL + DOX groups. Conclusion: This study implies that there are cardioprotective effects of MOL on DOX-induced cardiotoxicity.

Anionic N-heterocyclic carbenes derived from sydnone imines such as molsidomine. Trapping reactions with selenium, palladium, and gold

“…In continuation of our interest in sydnone derived carbenes 45 we report here on N-heterocyclic carbenes of two sydnone imines, among those the carbene of Molsidomine. This orally active vasodilating drug for the prevention of angina pectoris attacks 47 is the subject of intense ongoing pharmacological research, [48][49][50][51][52] however, during the last decade not much effort has been directed toward its chemical properties. We present some surprising results in the light of the relationship between mesomeric betaines and Nheterocyclic carbenes.…”

Cycloadditions of anionic N-heterocyclic carbenes of sydnone imines

“…11 In comparison to sydnones, much less is known about sydnone imines. Concerning the biological activity, the NO donor and vasodilating drug Molsidomine (Corvasal, Corvaton, Molsidain, Molsidolat), however, is a prominent and widely applied sydnone imine to which interest has been directed with respect to antiarrhythmogenic, 12 anxiolytic, 13 cardioprotective, 14 and cerebral vasospasm-associated activities. 15 Sydnone methides are extremely rare and, to the best of our knowledge, no information is available concerning the biological activities.…”

The Protective Role of Molsidomine on the Cisplatin-Induced Ototoxicity

“…Rodriguez-Pena et al showed MOL reduced plasma levels of pro-inflammatory cytokines however it increases the levels of antiinflammatory cytokines in rats [26]. Taking into consideration the reduced oxidative damage caused by MOL treatment, all investigators attributed the protective actions of MOL to its antioxidative and anti-inflammatory activities [27].…”

“…MOL is transformed into the metabolite 3-morpholinosydnonimine (SIN-1), which spontaneously liberates nitric oxide (NO). Apart from its anti-anginal effects, it has been more recently reported that MOL exerts potent antioxidant, antiapoptotic and antiinflammatory effects [11][12][13]. Therefore, MOL treatment can exert beneficial effects against CIO which regarding with oxidative stress and production of excessive reactive radicals.…”