綠茶及右旋兒茶素與水楊酸鈉在順氯氨鉑引發的腎毒性於純系小鼠
的藥效評估
Effects of green tea , (+)-catechin and sodium salicylate on cisplatin induced nephrotoxicity in inbred mice
中文摘要
臨床上，化學治療藥物順氯氨鉑(cisplatin, CDDP)常用於治療固體癌，其引起的 腎毒性，常是限制臨床使用的主要因素。本研究利用低劑量 CDDP 連續投予小 鼠，引發腎炎模型，以綠茶及(+)-catechin 和 sodium salicylate 作為預防藥物，評 估在此腎炎之預防效果。
實驗以 6 週齡雌鼠(BALB/c mice)藉由事先投予綠茶濃縮劑(GT 75, 150, 300 mg/kg/d)及其純成分(+)-catechin（CAT 25, 50, 100 mg/kg/d）、化學藥品 sodium salicylate 100 mg/kg/d（S）、併用 CAT 50mg + S（S + C）來評估藥物對 CDDP 引 起腎毒性的預防效果。實驗以 N-acetyl- -D-glucosaminidase (NAG)、urinary creatinine (Ucr.)與 BUN 評估腎功能；腎組織以 PAS 染色觀察病理組織及免疫螢 光染色辨別其損傷部位之特異性抗原。
實驗結果顯示，GT 150 mg/kg/d、(+)-catechin 50 mg/kg/d 及 S + C 皆可改善腎功 能，組織學上腎小管受損的情形相較於對照組也較輕微。綜合實驗結果顯示，S + C 對於預防 CDDP 所引起的腎毒性效果最好。
英文摘要
Cisplatin(CDDP) is one of the most commonly used antineoplastic agent for the treatment of solid tumor. The CDDP induced nephrotoxicity is dose-related and cumulative. It is the major dose-limiting toxicity of cisplatin. We used an established CDDP induced nephrotoxicity in inbred mice model to evaluate the effect of green tea extract, (+)-catechin and sodium salicylate.
Before administration of CDDP(i.p. 5mg/kg/d on day 1 to day 5), BALB/c mice（6 week, female）were administered orally with green tea extract(GT 75, 150, 300 mg/kg/d), (+)-catechin(CAT 25, 50, 100 mg/kg/d) , sodium salicylate 100 mg/kg/d(S) and combination of CAT 50 mg/kg/d and S(S + C) once daily for 10 days(on day -5 to day 5).
Urinary N-acetyl-β-D-glucosaminidase(NAG), urinary creatinine (Ucr.)and BUN were determined. Renal tissues were served to histological examination (PAS stain and immunofluorescence staining). The antibodies including TNF- , p21, cyclin D1 was chosen to recognize the specific antigens, which deposited in injury sites.
The result showed that GT 150 mg/kg/d、(+)-catechin 50 mg/kg/d and S + C can
ameliorate renal damage. According to the study, the effect of S + C was superior to the other groups.
