The protective effect of Boesenbergia rotunda extract on cisplatin-exposed human embryonic kidney-293 cells by inhibiting the expression of kidney injury molecule-1, neutrophil gelatinase associated-lipocalin, NF-κB, and caspases

Abstract

Introduction: Acute kidney injury (AKI) is a major problem in platinum-based chemotherapy patients. Boesenbergia rotunda can induce the generation of osteoblast cells and significantly increase pancreatic antioxidant enzyme activities; therefore, this study aimed to investigate the cytotoxicity of cisplatin on human embryonic kidney-293 (HEK-293) cells and the protective impact of the ethanol extract of B. rotunda (EEBR) against such conditions. Methods: Cytotoxicity was assessed using the CCK-8/WST-8 reagent, while the protective activity was assayed on 1 µg/mL cisplatin-exposed HEK-293 cells by quantifying the expression of nephrotoxicity biomarkers, e.g., kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated-lipocalin (NGAL), nuclear factor-kappaB (NF-κB), apoptotic caspase-3, and caspase-7 genes, in cisplatin-exposed HEK-293 cells. Results: Cisplatin was confirmed as highly toxic against the HEK-293 cells (IC50 = 2.5145 μg/ mL), whereas quercetin was of moderate toxicity (IC50 = 185.6225 μg/mL). EEBR revealed an IC50 = 40.0655 μg/mL. Moreover, EEBR concentrations of 5, 10, and 20 µg/mL confirmed its remarkable protective activity against cisplatin-exposed HEK-293 cells (P=0.031, 0.014, 0.046, respectively) compared to the cisplatin-treated cell lines without treatment. The quantitative real-time polymerase chain reaction (PCR) revealed that a higher concentration of EEBR significantly suppressed the expression of Kim-1, while lower concentrations of EEBR significantly inhibited NGAL and NF-κB genes. Higher concentrations of EEBR reduced the expression of caspase-3. All concentrations of EEBR stimulated the expression of caspase-7. Conclusion: The significant protective activity observed in this study indicated that EEBR might be beneficial in protecting kidney cells against cisplatin.

The Nephroprotective Activity of Boesenbergia Rotunda Rhizome by Reducing Creatinine, Urea Nitrogen, Glutamic Pyruvic Transaminase, and Malondialdehyde Levels in the Blood and Attenuating the Expression of Havcr1 (KIM-1), Lcn2 (NGAL), Casp3, and Casp7 Genes in the Kidney Cortex of Cisplatin-Induced Sprague-Dawley Rats

“…24 Moreover, a recent study reported that B. rotunda could induce osteoblast cell proliferation 25 and significantly increase pancreatic antioxidant enzyme activities (glutathione, superoxide dismutase, and catalase). 26 Until recently, the nephroprotective activity of B. rotunda has been explored very limitedly, however, EEBR was confirmed for its protective effect on cisplatin-exposed human embryonic kidney-293 cells, 27 thus, this present study aims to investigate the nephroprotective mechanism of EEBR in cisplatin-induced male Sprague-Dawley rats by measuring the general diagnostic markers of nephrotoxicity (SCr and BUN) and the liver function parameters (glutamic oxaloacetic transaminase or GOT and glutamic pyruvic transaminase or GPT), the % relative weight of the kidney, malondialdehyde (MDA) level in the kidney, kidney histopathology, the expression of AKI biomarkers (KIM-1 and NGAL) and apoptotic pathway proteins (Casp3 and Casp7) in the kidney cortex of the rats were also evaluated using the reverse transcriptionpolymerase chain reaction (RT-PCR).…”