Pyrocatechol Alleviates Cisplatin-Induced Acute Kidney Injury by Inhibiting ROS Production

Abstract

As one of the most common cancer chemotherapy drugs, cisplatin is widely used in cancer management. However, cisplatin-induced nephrotoxicity occurs in patients who receive this drug. This study is aimed at developing therapeutic agents that effectively alleviate the nephrotoxic effects during cisplatin treatment. We identified a compound named pyrocatechol (PCL) from a natural product library that significantly alleviated cisplatin-induced cytotoxicity in vitro. Pyrocatechol treatment substantially ameliorated cisplatin (20 mg · kg-1) treatment-induced neuropathological indexes, including inflammatory cell infiltration and apoptosis, in vivo. Mechanistically, pyrocatechol significantly prevented oxidative stress-induced apoptosis by activating glutathione peroxidase 4 (GPX4) to reduce reactive oxygen species (ROS) accumulation in cisplatin-treated cells. In addition, pyrocatechol significantly inhibited ROS-induced JNK/P38 activation. Thus, we found that pyrocatechol prevents ROS-mediated JNK/P38 MAPK activation, apoptosis, and cytotoxicity through GPX4. Our study demonstrated that pyrocatechol is a novel therapeutic agent against cisplatin-induced kidney injury.

A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction through dual-targeting mitochondrial and nuclear G4 enriched genome

“…In terms of mitochondrial dysfunction, cisplatin has been shown to have significant effects on that [43,55,56]. One of the mechanisms underlying cisplatin-induced mitochondrial toxicity is the generation of ROS, leading to oxidative stress-induced cell death, which is also a well-defined source of cisplatin-induced side effects [57][58][59]. In this regard and notably, Pt-ttpy does not function like typical Pt complexes, likely for cisplatin and Pt-tpy, as it neither induces general ROS nor mt specific ROS production in both cancer cell lines and primary tissue cells for short and long time (Figs.…”

Yiqi Chutan Formula Reverses Cisplatin-Induced Apoptosis and Ferroptosis of Skeletal Muscle by Alleviating Oxidative Stress

“…20 However, for normal cells with slow division, the damage caused by cisplatin is mainly closely related to ROS. 21,22 Our in vitro and in vivo experiments have demonstrated that cisplatin can lead to increased ROS levels in muscle cells, and this cisplatin-induced ROS can be effectively cleared by YCF and NAC. This may be related to the active ingredients in YCF.…”

A G-quadruplex-binding platinum complex induces cancer mitochondrial dysfunction in vitro and in vivo independently of ROS induction

“…In terms of mitochondrial dysfunction, cisplatin has been shown to have significant effects on that (37) (52,53). One of the mechanisms underlying cisplatin-induced mitochondrial toxicity is the generation of ROS, leading to oxidative stress-induced cell death, which is also a well-defined source of cisplatin-induced side effects (54) (55,56). In this regard and notably, Pt-ttpy does not function like typical Pt complexes, likely for cisplatin and Pt-tpy, as it neither induces general ROS nor mt specific ROS production in both cancer cell lines and primary tissue cells for short and long time (Fig.…”