Domitrović Robert, Potočnjak Iva, Crnčević-Orlić Zeljka, Škoda Marko
Department of Chemistry and Biochemistry, Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia.
Medical Faculty, University of Rijeka, 51000 Rijeka, Croatia.
Food Chem Toxicol. 2014 Apr;66:321-8. doi: 10.1016/j.fct.2014.02.002. Epub 2014 Feb 8.
Rosmarinic acid (RA) is a natural phenolic compound with a broad range of applications, from food preservatives to cosmetics. Increasing amounts of evidence suggests its beneficial effects against various pathological conditions. The aim of this study was to investigate the therapeutic activity of rosmarinic acid (RA) against cisplatin (CP)-induced nephrotoxicity. RA was administered by oral gavage at doses of 1, 2 and 5mg/kg for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Twenty four hours later, mice were sacrificed. Treatment with RA significantly ameliorated histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP. Oxidative stress induced by CP, evidenced by increased renal 4-hydroxynonenal (4-HNE), cytochrome P450 2E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced by RA administration. Moreover, RA inhibited the expression of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-α (TNF-α), indicating the inhibition of inflammation. Additionally, RA exhibited antiapoptotic activity through the reduction of p53, phosphorylated p53 and active caspase-3 expression in the kidneys. These findings show that RA ameliorates CP-induced oxidative stress, inflammation and apoptosis in the kidneys. The nephroprotective activity of RA could be, at least in part, attributed to reduced CYP2E1 expression.
迷迭香酸（RA）是一种天然酚类化合物，具有广泛的应用，从食品防腐剂到化妆品。越来越多的证据表明其对各种病理状况具有有益作用。本研究的目的是探讨迷迭香酸（RA）对顺铂（CP）诱导的肾毒性的治疗活性。在腹腔注射CP（13mg/kg）后48小时，连续两天以1、2和5mg/kg的剂量通过口服灌胃给予RA。24小时后，处死小鼠。RA治疗显著改善了CP诱导的组织病理学变化以及血清肌酐和血尿素氮（BUN）的升高。CP诱导的氧化应激通过肾4-羟基壬烯醛（4-HNE）、细胞色素P450 2E1（CYP2E1）和血红素加氧酶（HO-1）表达增加得以证实，给予RA后显著降低。此外，RA抑制核因子-κB（NF-κB）和肿瘤坏死因子-α（TNF-α）的表达，表明炎症受到抑制。另外，RA通过降低肾脏中p53、磷酸化p53和活化的半胱天冬酶-3的表达表现出抗凋亡活性。这些发现表明RA改善了CP诱导的肾脏氧化应激、炎症和凋亡。RA的肾保护活性至少部分归因于CYP2E1表达的降低。
