Prince Paula Denise, Fischerman Laura, Toblli Jorge E, Fraga Cesar G, Galleano Monica
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Analitica y Fisicoquimica, Cátedra de Fisicoquímica, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina.
Laboratorio de Medicina Experimental, Hospital Alemán, Buenos Aires, Argentina.
Redox Biol. 2017 Apr;11:342-349. doi: 10.1016/j.redox.2016.12.023. Epub 2016 Dec 22.
This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by LPS administration in rats. Male Sprague Dawley rats were fed for 4 days a diet without or with supplementation with (-)-epicatechin (80mg/kg BW/d), and subsequently i.p. injected with lipopolysaccharide (LPS). Six hours after injection, LPS-treated rats exhibited increased plasma creatinine and urea levels as indicators of impaired renal function. The renal cortex of the LPS-treated rats showed: i) increased expression of inflammatory molecules (TNF-α, iNOS and IL-6); ii) activation of several steps of NF-κB pathway; iii) overexpression of TLR4, and iv) higher superoxide anion production and lipid peroxidation index in association with increased levels of gp91 and p47 (NOX2) and NOX4. Pretreatment with dietary (-)-epicatechin prevented the adverse effects of LPS challenge essentially by inhibiting TLR4 upregulation and NOX activation and the consequent downstream events, e.g. NF-kB activation.
本研究探讨了(-)-表儿茶素预防脂多糖(LPS)诱导的大鼠肾损伤的能力。将雄性Sprague Dawley大鼠分为两组,一组喂食4天无(-)-表儿茶素补充的饲料,另一组喂食添加了(-)-表儿茶素(80mg/kg体重/天)的饲料,随后腹腔注射脂多糖(LPS)。注射6小时后,LPS处理的大鼠血浆肌酐和尿素水平升高,提示肾功能受损。LPS处理大鼠的肾皮质表现为:i)炎症分子(TNF-α、iNOS和IL-6)表达增加;ii)NF-κB通路多个步骤激活;iii)TLR4过表达;iv)超氧阴离子产生增加和脂质过氧化指数升高,同时gp91和p47(NOX2)及NOX4水平升高。膳食(-)-表儿茶素预处理主要通过抑制TLR4上调和NOX激活以及随后的下游事件(如NF-κB激活)来预防LPS攻击的不良影响。