期刊
LATIN AMERICAN JOURNAL OF PHARMACY
卷 39, 期 6, 页码 1176-1186出版社
COLEGIO FARMACEUTICOS PROVINCIA DE BUENOS AIRES
关键词
antioxidant and anti-inflammatory; dimethyl fumarate; high mobility group box-1; ischemia reper-fusion injury; toll like receptors signaling pathway
Inflammation plays pivotal role in pathogenesis of renal induced isquemia reperfusion (IRI). This is achieved by enhancing the production of proinflammatory cytokines, chemokines, and immunomediators. This study aims to investigate the protective effects of dimethyl fumarate (DMF) treatment in renal IRI of rat model by targeting HMGB-1/TLRs signaling pathway. Twenty four Sprague Dawley rats were randomly divided into four groups: Sham group (operated group but without IR), Control group (ischemia 30 min and reperfusion 2 h), Vehicle group (as in control + DMSO), and DMF group (as in control + 25 mg/kg DMF). After 2 h of reperfusion the blood was drawn and kidneys harvested to assess BUN, Scr, NGAL, HMGB-1, TLR2 and TLR4 in addition to histological examination. Rats in control and vehicle groups demonstrated significant elevation in BUN, Scr, and NGAL. Furthermore, HMGB-1 was significantly translocated into cytoplasm and released to extracellular space. Immunohistochemically, the expression of TLR2 and TLR4 were significantly increased. Kidneys of pretreated rats with DMF showed histological and functional amelioration as evidenced by significant reduction in BUN, Scr and NGAL. The anti-inflammatory effects of DMF appeared clearly through the significant inhibition of HMGB-1 secretion in addition to significant reduction of TLR2 and 4 proteinexpression. DMF alleviated the kidney damage induced by bilateral renal IR, and these protective impacts may be done by inhibition of HMGB-1/TLR pathway.
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