| dc.description.abstract | Introduction Pulmonary Arterial Hypertension (PAH) is a life threatening and devastating disease with a high morbidity and mortality by an unusual increase in pulmonary artery pressure and pulmonary vascular resistance. Methylsulfonylmethane(MSM) is naturally occurring organic sulphur that is known as an anti-oxidant, anti-inflammatory and antiproilferative compound. Objective The aim of this study was to investigate the effect of MSM on hemodynamic functions, oxidative stress and mRNA expressions of angiotensinogen, Endothelin-1 (ET-1) and Transforming Growth Factor (TGF-1) in rats with monocrotaline (MCT)-induced PAH.Materials and Methods Wistar rats were randomly assigned to 28 and 38-days treatments. MSM was administered to rats at 100, 200, and 400 mg/kg/day doses either 10 days before or 14 days after a single dose of 60mg/kg, IP, monocrotaline(MCT). Rats were anesthetized with pentobarbital and ventricular hemodynamic indices were determined using Powerlab ADinstrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Right ventricle (RV) tissue samples were obtained to evaluate changes in the inflammatory genes expression using RT-PCR assay.Results Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-Px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. MSM treatment induced an increase in GSH along with the index of the redox state GSH/GSSG in MCT-induced pulmonary arterial hypertensive rats The value of RV/(LV+S) ratio was significantly higher in rats exposed to MCT, which was significantly reversed by MSM treatment (P < 0.01). The expression levels of angiotensinogen, ET-1 and TGF- 1 significantly reduced at efficient dose of MSM in MCT-induced pulmonary arterial hypertensive rats (P < 0.05). Levels of ET-1 mRNA transcript in MSM-treated pulmonary hypertensive rats decreased, even as compared to the values corresponding to normotensive control rats (P <0.01).Conclusion The Results of this study suggest that harmful effects of MCT induced PAH on the RV function could be attenuated by antioxdant actions of MSM through the suppression of local Renin-Angiotensin-Aldestron System (RAAS) along with associated growth-promoting factors such as Transforming Growth Factor (TGF-1) and Endothelin-1 (ET-1). In addition, long term administration of MSM could exert protective antioxidative effects through the induction of CAT, SOD, and GSH-Px activities along with associated reducing agents, such as GSH in rats with monocrotaline induced right heart failure Keywords Methylsulfonylmethane; Monocrotaline induced pulmonary hypertension; Oxidative stress; Inflammation; Gene expression | |
