Protective effects of cysteine analogues on acute myocardial ischemia: novel modulators of endogenous H(2)S production.
The current study was designed to evaluate the pharmacologic effects of three novel cysteine-containing compounds: S-propyl-l-cysteine (SPC), S-allyl-l-cysteine (SAC), and S-propargyl-l-cysteine (SPRC) on H(2)S production and antioxidant defenses in an acute myocardial infarction (MI) rat model. The enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as glutathione redox status and malonaldehyde (MDA) content, also were determined. All three compounds were found to preserve SOD and GPx activities and also tissue GSH levels while reducing the formation of the lipid peroxidation product MDA in ventricular tissues. With immunfluorescence assays, we observed the expression of CSE and Mn-SOD. The morphologic changes of the cardiac cells are seen with both light and electron microscopy. The corresponding pathologic alterations were characterized mainly as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. Propargylglycine, a selective inhibitor of CSE, abolished the protective effects of each compound used in the current model. Our study provides novel evidence that SPC, SAC, and SPRC have cardioprotective effects in MI by reducing the deleterious effects of oxidative stress by modulating the endogenous levels of H(2)S and preserving the activities of antioxidant defensive enzymes like SOD.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
Qian
Q
Wang
Xian-Li
XL
Wang
Hong-Rui
HR
Liu
Peter
P
Rose
Yi-Zhun
YZ
Zhu
D000393:Air Pollutants / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000393:Air Pollutants; D000975:Antioxidants; D002316:Cardiotonic Agents; D012333:RNA, Messenger; D008315:Malondialdehyde; C028742:S-propylcysteine; C065299:S-allylcysteine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003545:Cysteine; D006862:Hydrogen Sulfide