Abstract
Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL A. absinthium extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the A. absinthium extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of A. absinthium extract and its mechanism of action against cisplatin-induced renal injury.
Highlights
Cis-diamminedichloroplatinum (II) was first reported as an anti-cancer agent in the 1970s and named cisplatin [1,2,3]
A. absinthium extract was 61.0 ± 9.2%, 81.9 ± 10.1%, and 91.9 ± 4.6%, respectively. These results suggest that A. absinthium extract has a substantial protective effect against the reduction in cell viability caused by cisplatin treatment
The protection of A. absinthium extract against reactive oxygen species (ROS) increase under cisplatin treatment were shown in Figure 2B by the decrease in fluorescent level of NAC and A. absinthium-extract-treated groups compared to cisplatin-treated group
Summary
Cis-diamminedichloroplatinum (II) was first reported as an anti-cancer agent in the 1970s and named cisplatin [1,2,3]. Clinical research has revealed that cisplatin causes renal injury in patients with cancer, which continues to limit its use [4,5,6]. Similar to many other chemotherapy drugs, cisplatin causes a wide range of adverse effects on normal tissues such as ototoxicity [7], cardiotoxicity, nephrotoxicity, hematological toxicity, gastrointestinal toxicity, hepatotoxicity, and neurotoxicity [8]. Among these side effects of cisplatin, nephrotoxicity is considered to be the most severe and to cause the most long-lasting harm to the body [9].
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