Amarasiri Sachinthi S, Attanayake Anoja P, Arawwawala Liyanage D A M, Mudduwa Lakmini K B, Jayatilaka Kamani A P W
Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Ruhuna, Galle, Sri Lanka.
Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Galle, Sri Lanka.
J Tradit Complement Med. 2023 May 31;13(5):500-510. doi: 10.1016/j.jtcme.2023.05.007. eCollection 2023 Sep.
Doxorubicin (DOX) is a chemotherapeutic drug with potential nephrotoxic effects on patients who are on cancer chemotherapy. An interest has been observed in using natural products to ameliorate the potential side effects of DOX. The present study is to investigate the cellular mechanisms underlying the protective effects of L. (BP) (Acanthaceae) extracts, DOX-induced acute kidney injury (AKI).
Hexane (25 mg/kg/day), ethyl acetate (80 mg/kg/day), n-butanol (70 mg/kg/day), and water (120 mg/kg/day) extracts of BP, were administered to DOX-induced (5 mg/kg (2500 μL/kg), ip) Wistar rats for four consecutive weeks. At the end of the study, investigations were carried out for the assessment of biomarkers of nephrotoxicity, oxidative stress, inflammation, and apoptosis.
Treatments with BP extracts significantly reversed DOX-induced elevations in serum and urine biochemical markers of nephrotoxicity (serum creatinine; 21-33%, blood urea nitrogen; 26-58%, β-microglobulin; 19-22% and urine total protein; 47-67%). There was a reduction in the levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde in kidney homogenates of rats treated with the n-butanol extract (by 43, 62, and 24%) and water extract (by 57%, 85%, and 26%) (p < 0.05). Immunohistochemical expression of the pro-apoptotic B-cell associated X protein was reduced while the anti-apoptotic B-cell lymphoma gene product 2 protein was increased in kidney tissues after the treatments with BP extracts.
The selected BP extracts significantly ameliorated DOX-induced AKI. The findings would open new vistas for the development of a drug using the BP extracts to minimize DOX-induced AKI in cancer patients.
阿霉素（DOX）是一种化疗药物，对接受癌症化疗的患者具有潜在肾毒性作用。人们已对使用天然产物改善DOX的潜在副作用产生兴趣。本研究旨在探讨爵床属（BP）（爵床科）提取物对DOX诱导的急性肾损伤（AKI）保护作用的细胞机制。
将BP的己烷提取物（25毫克/千克/天）、乙酸乙酯提取物（80毫克/千克/天）、正丁醇提取物（70毫克/千克/天）和水提取物（120毫克/千克/天）连续四周给予DOX诱导（5毫克/千克（2500微升/千克），腹腔注射）的Wistar大鼠。在研究结束时，进行了肾毒性、氧化应激、炎症和凋亡生物标志物的评估调查。
BP提取物治疗显著逆转了DOX诱导的肾毒性血清和尿液生化标志物升高（血清肌酐；21 - 33%，血尿素氮；26 - 58%，β-微球蛋白；19 - 22%和尿总蛋白；47 - 67%）。用正丁醇提取物（分别降低43%、62%和24%）和水提取物（分别降低57%、85%和26%）处理的大鼠肾匀浆中肿瘤坏死因子-α、白细胞介素-1β和丙二醛水平降低（p < 0.05）。用BP提取物处理后，肾组织中促凋亡的B细胞相关X蛋白的免疫组化表达降低，而抗凋亡的B细胞淋巴瘤基因产物2蛋白增加。
所选BP提取物显著改善了DOX诱导的AKI。这些发现将为开发一种使用BP提取物的药物以最小化癌症患者DOX诱导的AKI开辟新前景。
