Protective effect of rosuvastatin pretreatment against acute myocardial injury by regulating Nrf2, Bcl-2/Bax, iNOS, and TNF-α expressions affecting oxidative/nitrosative stress and inflammation
Autor: | Faheem Sultan, Rajdeep Kaur, Najeeb U Tarfain, Arshad H Mir, Vinod K Dumka, Suresh K Sharma, Simrat P Singh Saini |
---|---|
Rok vydání: | 2022 |
Předmět: |
Male
Dose-Response Relationship Drug NF-E2-Related Factor 2 Health Toxicology and Mutagenesis Isoproterenol Myocardial Infarction Nitric Oxide Synthase Type II nutritional and metabolic diseases General Medicine Protective Agents Toxicology Antioxidants Rats Disease Models Animal Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 Animals Hydroxymethylglutaryl-CoA Reductase Inhibitors Rats Wistar Rosuvastatin Calcium Adaptor Proteins Signal Transducing |
Zdroj: | Human & Experimental Toxicology. 41:096032712110660 |
ISSN: | 1477-0903 0960-3271 |
DOI: | 10.1177/09603271211066065 |
Popis: | Cardiovascular disorders are the leading cause of death globally. Rosuvastatin is a member of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) with many pleiotropic properties. This study investigated cardioprotective effects of rosuvastatin in isoprenaline-induced myocardial injury. Male rats were given rosuvastatin (1, 5, or 10 mg/kg, oral) daily for 1 week and on seventh and eighth day isoprenaline (150 mg/kg, subcutaneous) was given to induce cardiac injury. On ninth day, rats were euthanized and different samples were harvested for analysis. Isoprenaline administration resulted in increased cardiac mass, increased cardiac injury marker levels (cTnI, CK-MB, ALT, and AST), increased lipid/protein oxidation, and increased cardiac nitrite levels. It also decreased superoxide dismutase, CAT, GST, and glutathione reductase activities, and total antioxidant activity. Isoprenaline also increased TNF-α and IL-6 levels. Decreased mRNA expression of Nrf2 and Bcl-2 along with increased mRNA expression of Bax, eNOS and iNOS genes was observed in isoprenaline treated animals. Histopathological evaluations of rosuvastatin pre-treated groups showed reduction of myocardial necrosis. Pretreatment with rosuvastatin (5 and 10 mg/kg) reduced many of these pathological changes. The current study showed that rosuvastatin significantly reduces myocardial injury induced by isoprenaline. |
Databáze: | OpenAIRE |
Externí odkaz: |