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Protective Effects of Dendropanax morbifera against Cisplatin-Induced Nephrotoxicity without Altering Chemotherapeutic Efficacy

1
Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea
2
Division of Molecular Biology, College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Korea
*
Authors to whom correspondence should be addressed.
Antioxidants 2019, 8(8), 256; https://doi.org/10.3390/antiox8080256
Received: 27 June 2019 / Revised: 25 July 2019 / Accepted: 29 July 2019 / Published: 30 July 2019
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Abstract

Use of the chemotherapeutic agent cisplatin (CDDP) in cancer patients is limited by the occurrence of acute kidney injury (AKI); however, no protective therapy is available. We aimed to investigate the renoprotective effects of Dendropanax morbifera water extract (DM) on CDDP-induced AKI. Male Sprague-Dawley rats (six animals/group) received: Vehicle (control); CDDP (6 mg/kg, intraperitoneally (i.p.); DM (25 mg/kg, oral); or DM + CDDP injection. CDDP treatment significantly increased blood urea nitrogen (BUN), serum creatinine (sCr), and pro-inflammatory cytokines (IL-6 and TNF-α), and severely damaged the kidney architecture. Urinary excretion of protein-based AKI biomarkers also increased in the CDDP-treated group. In contrast, DM ameliorated CDDP-induced AKI biomarkers. It markedly protected against CDDP-induced oxidative stress by increasing the activity of endogenous antioxidants and reducing the levels of pro-inflammatory cytokines (IL-6 and TNF-α). The protective effect of DM in the proximal tubules was evident upon histopathological examination. In a tumor xenograft model, administration of DM enhanced the chemotherapeutic activity of CDDP and exhibited renoprotective effects against CDDP-induced nephrotoxicity without altering chemotherapeutic efficacy. Our data demonstrate that DM may be an adjuvant therapy with CDDP in solid tumor patients to preserve renal function. View Full-Text
Keywords: cisplatin; Dendropanax morbifera; renoprotective effect; antioxidants; chemotherapy; xenograft model cisplatin; Dendropanax morbifera; renoprotective effect; antioxidants; chemotherapy; xenograft model
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Kim, J.S.; Kim, K.S.; Son, J.Y.; Kim, H.R.; Park, J.H.; Lee, S.H.; Lee, D.E.; Kim, I.S.; Lee, K.Y.; Lee, B.M.; Kwak, J.H.; Kim, H.S. Protective Effects of Dendropanax morbifera against Cisplatin-Induced Nephrotoxicity without Altering Chemotherapeutic Efficacy. Antioxidants 2019, 8, 256.

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