Protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of nitric oxide formation in aged and ovariectomized rats
| Autor: | Hong Yin, Zhi-Peng Luan, Ru Wang, Shi Zhenguo, Yongsheng Yu, Hu Jing, Guo Daihong |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Aging Simvastatin medicine.medical_specialty Nitric Oxide Synthase Type III Ovariectomy Nitric Oxide medicine.disease_cause Cell Line Nitric oxide Rats Sprague-Dawley Superoxide dismutase chemistry.chemical_compound Internal medicine Hyperlipidemia Animals Humans Medicine Pharmacology Osteoblasts biology business.industry nutritional and metabolic diseases Hydrogen Peroxide medicine.disease Rats Nitric oxide synthase Heme oxygenase Oxidative Stress Endocrinology chemistry biology.protein Ovariectomized rat Osteoporosis Female lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors business Oxidative stress medicine.drug |
| Zdroj: | European Journal of Pharmacology. 674:200-206 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2011.11.024 |
| Popis: | Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been used as a cholesterol-lowering drug to treat hyperlipidemia clinically. In recent years, accumulating evidence indicates the possible beneficial effect of statins on osteoporosis. The aim of present study was to investigate whether protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of nitric oxide (NO) formation in aged and ovariectomized rats. The aged and ovariectomized rats were used as two models of osteoporosis for evaluation of the effect of simvastatin. It was found that simvastatin abated oxidative stress, increased NO production, subsequently attenuating osteoporosis in two models. In the in vitro studies, the protective effects against H(2)O(2)-induced cell injury were examined in the MG-63 human osteoblastic cells. It was found that simvastatin ameliorated H(2)O(2)-induced cell loss and cell apoptosis and increased alkaline phosphatase (ALP) activity in osteoblastic cells. Simvastatin abated oxidative stress through enhancing catalase, heme oxygenase 1 (HO-1), and superoxide dismutase (SOD) activity and suppressing NADPH oxidase activity. In addition, simvastatin raised nitric oxide synthase (NOS) activity and eNOS expression at basal condition; inhibited NOS activity and iNOS expression when treated with H(2)O(2). In conclusion, protection against osteoporosis by statins is linked to a reduction of oxidative stress and restoration of NO formation in aged and ovariectomized rats. |
| Databáze: | OpenAIRE |
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