白藜芦醇对5-氟尿嘧啶所致大鼠肾毒性的治疗作用

Elias Adikwu, Innocent Biradee, Temitope Ogungbaike
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引用次数: 4

摘要

背景:预防5-氟尿嘧啶(5-FU)引起的肾毒性可提高患者的治疗依从性。目的与目的:研究白藜芦醇(resveratrol, RES)对5- fu所致大鼠肾毒性的预防作用。材料与方法:选用成年雄性白化大鼠40只,随机分为8组,每组n = 5只。A组(对照组)腹腔灌胃生理盐水0.2 mL, B-D组分别灌胃RES 10、20、40 mg/kg,连续5 d。E组患者给予5- fu每日20 mg/kg,连用5 d。F-H组每日分别给予RES 10 mg/kg + 5- fu 20 mg/kg、RES 20 mg/kg + 5- fu 20 mg/kg、RES 40 mg/kg + 5- fu 20 mg/kg,连续5 d。处死大鼠后采集血样,测定血清肾功能生物标志物。评估肾脏的氧化应激标志物和组织学。结果:与对照组相比,5- fu治疗大鼠血清肌酐、尿素和尿酸水平显著(P < 0.001)升高,而总蛋白、白蛋白、钾、钠、氯和碳酸氢盐水平显著(P < 0.001)降低。与对照组相比,5- fu处理的大鼠肾脏超氧化物歧化酶、谷胱甘肽、谷胱甘肽过氧化物酶和过氧化氢酶水平显著(P < 0.001)降低,而丙二醛水平显著升高。此外,5- fu处理的大鼠肾脏出现小管坏死和肾小球萎缩。与5-FU相比,添加10 mg/kg (P < 0.05)、20 mg/kg (P < 0.01)和40 mg/kg RES (P < 0.001)的大鼠肾毒性变化明显消失。结论:RES对5-FU所致肾毒性有一定的治疗作用。
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Therapeutic benefit of resveratrol in 5-fluorouracil-induced nephrotoxicity in rats
Background: The prevention of nephrotoxicity caused by 5-fluorouracil (5-FU) can improve patients' adherence to treatment.Aim and Objective: This study assessed the ability of resveratrol (RES) to prevent 5-FU-induced nephrotoxicity in rats. Materials and Methods: Forty adult male albino rats randomized into eight groups of n = 5 were used. Group A (control) was administered with 0.2 mL of normal saline intraperitoneally (i.p.), whereas Groups B-D were administered with 10, 20, and 40 mg/kg of RES daily for 5 days respectively. Group E was administered with 20 mg/kg of 5-FU ip daily for 5 days. Groups F-H were administered with 10 mg/kg of RES + 20 mg/kg of 5-FU, 20 mg/kg of RES + 20 mg/kg of 5-FU, and 40 mg/kg of RES + 20 mg/kg of 5-FU ip daily for 5 days, respectively. Blood samples were collected after rats were sacrificed and evaluated for serum renal function biomarkers. Kidneys were evaluated for oxidative stress markers and histology. Results: Serum creatinine, urea, and uric acid levels were significantly (P < 0.001) increased, whereas total protein, albumin, potassium, sodium, chloride, and bicarbonate levels were significantly (P < 0.001) decreased in 5-FU-treated rats when compared to control. Kidney superoxide dismutase, glutathione, glutathione peroxidase, and catalase levels were significantly (P < 0.001) decreased, whereas malondialdehyde levels were significantly increased in 5-FU-treated rats when compared to control. Furthermore, the kidneys of 5-FU-treated rats showed tubular necroses and atrophic glomeruli. The aforementioned nephrotoxic changes were significantly abrogated in rats supplemented with 10 mg/kg (P < 0.05), 20 mg/kg (P < 0.01), and 40 mg/kg (P < 0.001) of RES when compared to 5-FU. Conclusion: RES may have therapeutic benefit in nephrotoxicity caused by 5-FU.
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