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

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.

Natural products: potential treatments for cisplatin-induced nephrotoxicity

“…Potential natural product treatments for cisplatin-induced nephrotoxicity classified by chemical structures. Administration of naringenin and hesperetin combination downregulates FAK and p38 signaling pathways [131] Galangin Inhibits ERK and NF-κB signaling, RIP1/ RIP3-dependent necroptosis, oxidative stress, inflammation [180] Quercetin and galangin combination enhances anti-inflammatory effect [181] Biochanin A Inhibits inflammatory response and p53 apoptosis [182] Formononetin and biochanin A modulate NF-κB/p-AKT signaling molecules [ Reduces oxidative stress, inflammation and apoptosis, reduces COX-2 and iNOS expression, sirt1/NF-κB and caspase signaling pathway, PI3K/AKT/Apoptosis signaling pathways [98,99,[189][190][191][192][193] Panax notoginseng saponins Increases autophagy, BCL-2, reduces mitochondria-mediated endogenous apoptosis, HIF-1α/mitochondria/ROS pathway [194] Panax notoginseng saponins could increase the gastrointestinal tract absorption of aspirin and salicylic acid [195] Saponins Toxic study revealed ligustrazine was low toxic, LD 50 was larger than 5 g/kg, both the level of ALT and AST and histopathology in the liver and kidney exhibited no distinctions between the tetramethylpyrazine, resveratrol, and curcumin (TRC) combination [198]…”

“…Notably, protocatechuic aldehyde blocks cisplatin-induced AKI by suppressing Noxmediated oxidative stress and inflammation without affecting the antitumor activity of cisplatin [127]. In addition, whortleberry, tangeretin, cynaroside, resveratrol, Dendropanax morbifera, troxerutin, and meclofenamic acid also have certain inhibitory effects on nephrotoxicity [128][129][130][131][132][133].…”

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

“…Acute kidney injury (AKI) is a disease with high morbidity and mortality, which is characterized by a rapid loss of kidney function [1]. The most common causes of AKI include nephrotoxic drugs, renal ischemia-reperfusion (IR), sepsis, cardiac disease, hypertension, and diabetes mellitus.…”

Potential Gonado-Protective Effect of Cichorium endivia and Its Major Phenolic Acids against Methotrexate-Induced Testicular Injury in Mice

“…Many plants are the main sources for bioactive compounds that can be used to relieve diseases [ 81 ]. For instance, phytomedicine and plant-derived antioxidants are considered a prosperous strategy for alleviating chemotherapy-induced organ toxicities [ 28 , 82 , 83 , 84 , 85 ]. As a result, we aimed to evaluate the possible testiculo-protective effect of C. endivia L. crude extract, phenolic fraction, and isolated coumaric, vanillic, and ferulic acids against MTX-induced testicular injury in mice.…”