Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Korea.
Biol Pharm Bull. 2011;34(9):1508-13. doi: 10.1248/bpb.34.1508.
Previously, the authors demonstrated that the triterpenoid glycoside niga-ichigoside F₁ (NIF₁) and its aglycone 23-hydroxytormentic acid (23-HTA) isolated from the unripe fruits of Rubus coreanus (Rosaceae) ameliorate cisplatin-induced toxicity in renal epithelial LLC-PK₁ cells. In the present study, the nephroprotective effects of NIF₁ and 23-HTA were investigated in Sprague-Dawley rats with acute renal injury induced by a single intraperitoneal (i.p.) injection of cisplatin (7 mg/kg). Pretreatment with 23-HTA (10 mg/kg/d, per os (p.o.)) significantly reduced cisplatin-induced elevations in blood urea nitrogen (BUN) and serum creatinine level, whereas NIF₁ (10 mg/kg, p.o.) slightly reduced these levels. In addition, pretreatment with 23-HTA prevented cisplatin-induced hydroxyl radical generation, malondialdehyde (MDA) production, glutathione (GSH) depletion, and cisplatin-induced changes in the activities of oxidant and antioxidant enzymes in rat renal tissues. In addition, histopathological examinations showed that 23-HTA pretreatment reduced cisplatin-induced acute tubular necrosis and histological changes. In contrast, NIF₁ was found to have a slight or no influence on cisplatin-induced oxidative enzymes and acute tubular necrosis. Taken together, these results suggest that protective effect of 23-HTA pretreatment on cisplatin-induced renal damage is associated with the attenuation of oxidative stress and the preservation of antioxidant enzymes.
先前，作者证明了从悬钩子属植物（蔷薇科）未成熟果实中分离得到的三萜糖苷化合物 niga-ichigoside F₁（NIF₁）及其苷元 23-羟基苦杏仁酸（23-HTA）可改善顺铂诱导的肾上皮 LLC-PK₁ 细胞毒性。在本研究中，通过单次腹腔（i.p.）注射顺铂（7 mg/kg）诱导急性肾损伤的 Sprague-Dawley 大鼠中研究了 NIF₁ 和 23-HTA 的肾保护作用。23-HTA（10 mg/kg/d，口服（p.o.））预处理可显著降低顺铂诱导的血尿素氮（BUN）和血清肌酐水平升高，而 NIF₁（10 mg/kg，p.o.）则略有降低。此外，23-HTA 预处理可预防顺铂诱导的羟自由基生成、丙二醛（MDA）产生、谷胱甘肽（GSH）耗竭以及顺铂诱导的大鼠肾组织中氧化应激和抗氧化酶活性的改变。此外，组织病理学检查表明，23-HTA 预处理可减轻顺铂诱导的急性肾小管坏死和组织学变化。相比之下，NIF₁ 对顺铂诱导的氧化酶和急性肾小管坏死的影响较小或没有影响。综上所述，这些结果表明，23-HTA 预处理对顺铂诱导的肾损伤的保护作用与减轻氧化应激和维持抗氧化酶有关。
