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SIMVASTATIN REDUCESMORTALITY AND HEPATICINJURY AFTERHEMORRHAGE/RESUSCITATION IN RATS Borna ReljaMark LehnertKorbinian Seyboth2010 год

SIMVASTATIN REDUCES MORTALITY AND HEPATIC INJURY AFTER HEMORRHAGE/RESUSCITATION IN RATS
статья из журнала

Страница публикацииПубликация в OpenAlex
Аннотация: Statins are established in the prevention and therapy of chronic cardiovascular diseases because of inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A), thus lowering blood cholesterol levels. However, their cholesterol-independent effects include regulation of Rho/Rho-kinases (ROCK) and eNOS, proteins centrally involved in various models of acute inflammation. Therefore, we tested the hypothesis that simvastatin confers protection after rat hemorrhage/resuscitation (H/R) and wanted to elucidate the mechanisms involved. Fifty-two female Lewis rats (180-250 g) were pretreated with simvastatin 5 mg/kg per day or vehicle for 6 days (i.p.). Then, rats were hemorrhaged to a mean arterial pressure of 30 +/- 2 mmHg for 60 min and resuscitated. Control group underwent surgical procedures without H/R. Two hours after resuscitation, tissues were harvested. Mortality was assessed 72 h after H/R. Simvastatin pretreatment increased survival after H/R from 20% to 80%. Serum alanine aminotransferase after H/R increased 2.2-fold in vehicle as compared with simvastatin-treated rats. Histopathological analysis revealed decreased hepatic necrosis in simvastatin-treated rats after H/R. Hepatic oxidative (4-hydroxynonenal) and nitrosative (3-nitrotyrosine) stress, inflammatory markers (serum IL-6 and hepatic infiltration with polymorphonuclear leukocytes), and actin cytoskeleton rearrangements were decreased after simvastatin pretreatment compared with vehicle-treated rats after H/R. Simvastatin increased eNOS and heme oxygenase 1 expression and eNOS activation. Expression of Rho/Rho-kinase and myosin phosphatase targeting subunit, Thr-MYPT1, a marker for Rho-kinase activity, decreased after simvastatin treatment compared with vehicle-treated rats after H/R. Simvastatin pretreatment exerts beneficial effects in this model of acute inflammation by supporting protective mechanisms that are important for hepatic microcirculation after H/R.
Год издания: 2010
Авторы: Borna Relja, Mark Lehnert, Korbinian Seyboth, Fabian Bormann, Christoph Höhn, Christoph Czerny, Dirk Henrich, Ingo Marzi
Издательство: Lippincott Williams & Wilkins
Источник: Shock
Ключевые слова: Drug-Induced Hepatotoxicity and Protection, Peroxisome Proliferator-Activated Receptors, Alcohol Consumption and Health Effects
Другие ссылки: Shock (HTML)
journals.lww.com (HTML)
PubMed (HTML)