Plant‐Derived Agents for Counteracting Cisplatin‐Induced Nephrotoxicity

Abstract

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

Benzyl salicylate from the stems and stem barks of Cornus walteri as a nephroprotective agent against cisplatin-induced apoptotic cell death in LLC-PK1 cells

“…3 Cisplatin is especially toxic to the proximal tubule cells of the kidney, resulting in kidney dysfunction. 4 Recent cisplatin-targeted nephroprotection studies have focused on the search for natural products with enormous structural and chemical diversity, 5,6 because reducing cisplatininduced nephrotoxicity will not only maximize its clinical outcomes, but can be benecial to patients receiving cisplatin chemotherapy.…”

Unique Triterpenoid of Jujube Root Protects Cisplatin-induced Damage in Kidney Epithelial LLC-PK1 Cells via Autophagy Regulation

“…Among these, nephrotoxicity is considered to be a major concern as the kidneys are involved in the bio-transformation of various toxic chemicals, including anticancer drugs [3,4]. Moreover, cisplatin-induced toxicity resulted in a significant mortality rate of 50% to 60% [5]. These shortcomings have led to the development of novel therapeutic drugs and combination/synergistic strategies to overcome cisplatin-associated nephrotoxicity, without compromising its primary anticancer potential.…”

“…Although further research is necessary to substantiate the effects, we evaluated the potential mechanism of action of 3DC2ME as an adjuvant for cancer patients.Historically, plant-derived compounds or phytochemicals have been widely used to treat various ailments such as cancer. Evidence in support of phytochemicals counteracting cisplatin-induced nephrotoxicity has started emerging [5,6]. A number of studies have recognized either whole or part of Jujube (Ziziphus jujuba Mill., Rhamnaceae) as an outstanding source of various phytochemicals, triterpenoids, polysaccharides, amino acids, flavonoids, alkaloids, polyphenols, and cerebrosides [7-10].…”

Protective Effect of Panaxynol Isolated from Panax vietnamensis against Cisplatin-Induced Renal Damage: In Vitro and In Vivo Studies

“…In addition, the inflammatory response is linked to the cisplatin-induced renal tissue damage through the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), and IL-6 [26]. Natural products possessing potent antioxidant and anti-inflammatory properties are being evaluated against cisplatin-induced nephrotoxicity [27][28][29].Although differing in cell types and concentrations, considering the antioxidant and anti-inflammatory properties, panaxynol may possess a renoprotective effect. Therefore, we explored the mechanisms involved in the protective effect of panaxynol against cisplatin-induced renal damage in vitro and in vivo.…”

“…In addition, the inflammatory response is linked to the cisplatin-induced renal tissue damage through the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), and IL-6 [26]. Natural products possessing potent antioxidant and anti-inflammatory properties are being evaluated against cisplatin-induced nephrotoxicity [27][28][29].…”