Effects of endogenous sulfur dioxide on monocrotaline-induced pulmonary hypertension in rats¹

Abstract

Aim: The present study aimed to explore the protective effect of endogenous sulfur dioxide (SO 2 ) in the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Methods: Forty Wistar rats were randomly divided into the MCT group receiving MCT treatment, the MCT+L-aspartate-β-hydroxamate (HDX) group receiving MCT plus HDX treatment, the MCT+SO 2 group receiving MCT plus SO 2 donor treatment, and the control group. Mean pulmonary artery pressure (mPAP) and structural changes in pulmonary arteries were evaluated. SO 2 content, aspartate aminotransferase activity, and gene expression were measured. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), reduced glutathione (GSH), oxidized glutathione, and malondialdehyde (MDA) levels were assayed. Results: In the MCT-treated rats, mPAP and right ventricle/(left ventricle+septum) increased significantly (P<0.01), pulmonary vascular structural remodeling developed, and SOD, GSHPx, CAT, GSH, and MDA levels of lung homogenates significantly increased (P<0.01) in association with the elevated SO 2 content, aspartate aminotransferase activity, and gene expression, compared with the control rats. In the MCT+HDX-treated rats, lung tissues and plasma SO 2 content and aspartate aminotransferase activities decreased significantly, whereas the mPAP and pulmonary vascular structural remodeling were markedly aggravated with the decreased SOD, CAT, and GSH levels of lung tissue homogenates compared with the MCTtreated rats (P<0.01). In contrast, with the use of a SO 2 donor, the pulmonary vascular structural remodeling was obviously lessened with elevated lung tissue SOD, GSH-Px, and MDA content, and plasma SOD, GSH-Px, and CAT levels. Conclusion: Endogenous SO 2 might play a protective role in the pathogenesis of MCT-induced PH and promote endogenous antioxidative capacities.

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats

“…[49][50][51] Furthermore, HDX could inhibit AAT activities and the generation of endogenous SO 2 in both pulmonary tissues and myocardium. 17,18,36 The present results showed that compared with vehicle-treated cells, OA induced a marked reduction of SO 2 generation but a significant increase in O 2 À and OH À generation, which could be reversed by supplementation of SO 2 . HDX-treated cells generated significantly increased oxygen radicals and markedly upregulated caspase-3 cleavage and PARP expression, resulting in cell injury and apoptosis demonstrated by TUNEL and Hoechst staining.…”

“…14 Endogenous SO 2 protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats, 18 and might play a protective role in the pathogenesis of monocrotalin-induced pulmonary hypertension and promote endogenous antioxidative capacities, 36 suggesting that endogenous SO 2 was involved in the regulation of cardiovascular oxidative stress. 37 Regardless of recent research on the emerging protective role of endogenous SO 2 in maintaining homeostasis in vivo, little has been revealed To examine the role of the endogenous SO 2 /AAT1/AAT2 pathway in the development of ALI, we established a rat model of OA-induced ALI and determined the level of endogenous SO 2 /AAT1/AAT2 pathway.…”

Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats

“…The major pathways for the disposal of H 2 O 2 in cells are catalyzed by GSH-Px and catalase, which metabolize H 2 O 2 into water and oxygen. Du and coworkers 41 reported that endogenous SO 2 raised the antioxidant capacity in rats of monocrotaline-induced pulmonary hypertension. In this study, antioxidant activity demonstrated by SOD and GSH-Px in the myocardial tissue of ISO-treated rats decreased significantly.…”

Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis

“…Peripheral blood PMN cell culture and evaluation of PMN apoptosis by FCM Peripheral blood PMNs were cultured in RPMI-1640 medium at 37 °c in 5% cO 2 and treated with 30 mg/L LPS and different concentration of SO 2 (10,20, and 30 µmol/L SO 2 ) in vitro for 6 h for the detection of apoptosis-related protein expression using the Western blotting method. To determine the rate of apoptosis, PMNs were cultured for 24 h and then submitted to FCM.…”

“…SO 2 was also previously considered a risk factor for respiratory and cardiovascular disease [9] . Recently, studies have shown that SO 2 plays important pathophysiologic roles during many disease processes, including the attenuation of monocrotaline-induced pulmonary hypertension, the inhibition of hypoxic pulmonary vascular structural remodeling, protection against isoproterenol-induced myocardial injury, and the increase of myocardial antioxidant capacity [10][11][12] . However, the effects of SO 2 on ALI and its mechanisms are poorly understood.…”