The Ameliorative Effect of 23-Hydroxytormentic Acid Isolated from Rubus coreanus on Cisplatin-Induced Nephrotoxicity in Rats

• Published in: Biological & Pharmaceutical Bulletin 2011/09/01, Vol.34(9), pp.1508-1513
• Main Authors: Sohn, Se-Il, Rim, Hong-Kun, Kim, Yang-Hee, Choi, Jung-Hye, Park, Jae-Hoon, Park, Hee-Juhn, Choi, Jong-won, Kim, Soo-dong, Jeong, Seo-Young, Lee, Kyung-Tae
• Format: Article
• Language: English
• Subjects: 23-hydroxytormentic acid; Animals; Antineoplastic Agents - toxicity; antioxidant enzyme; Antioxidants - metabolism; Blood Urea Nitrogen; cisplatin; Cisplatin - toxicity; Creatinine - blood; Glutathione - metabolism; Hydroxyl Radical - metabolism; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; LLC-PK1 Cells; Male; Malondialdehyde - metabolism; nephrotoxicity; niga-ichigoside F1; oxidative stress; Rats; Rats, Sprague-Dawley; Rosaceae; Rubus; Swine; Triterpenes - pharmacology
• ISSN: 0918-6158; 1347-5215; 1347-5215
• 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.