Coenzyme Q10 protects Pc12 cells from cisplatin-induced DNA damage and neurotoxicity

Abstract

The purpose of this study was to investigate the neuroprotective effect of a water-soluble formulation of coenzyme Q10 (WS-CoQ10) in PC12 cells exposed to cisplatin, a chemotherapeutic agent with a dose-limiting factor due to neurotoxicity. In the cytokinesis-block micronucleus cytome assay (CBMN Cyt), WS-CoQ10 (at concentrations of 0.1, 0.5 and 1.0μgmL(-1)) protected PC12 cells from cisplatin-induced DNA damage (0.1μgmL(-1)), reducing the frequency of micronuclei (MNi) and nuclear buds (NBUDs). WS-CoQ10 did not alter the mRNA expression levels of Tp53 (at a concentration of 1.0μgmL(-1)) and exhibited neuroprotective activity by stimulating cisplatin-inhibited neurite outgrowth in nerve growth factor (NGF)-differentiated PC12 cells (at a concentration of 0.1μgmL(-1)). In conclusion, WS-CoQ10 protected the PC12 cells from cisplatin-induced DNA damage and neurotoxicity. Moreover, the neuroprotective effects of WS-CoQ10 suggest a possible application in chemotherapeutic protocols.

Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics—A Review

“…These cells possess neuronal cell features and respond positively to nerve growth factor. WS-CoQ10 showed neuroprotective effects on the PC12 cells, protection from cisplatin-induced DNA damage, and an increase in the total intracellular GSH [ 58 ]. The application of thiamine pyrophosphate significantly improved oxidative parameters in the brain tissue of rats treated with cisplatin [ 59 ].…”

Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study

“…It is present in the biological membranes of cellular organelles, such as peroxisomes and lysosomes, and is principally located in the inner mitochondrial membrane as part of the electron transport chain, which is responsible for adenosine triphosphate synthesis. [ 5 ] CoQ10 is considered a potent lipophilic antioxidant; it acts directly with free radicals or as a reducing agent for regenerating Vitamins E and C from their oxidized forms. [ 6 ] CoQ10 inhibits the generation of reactive oxygen species and lipid peroxidation products during free-radical scavenging, suppresses excess nitric oxide (NO) production, and prevents nitrative stress in tissues.…”

Genotoxic risk in humans and acute toxicity in rats of a novel oral high-dose coenzyme Q10 oleogel

“…CoQ 10 is an endogenously produced compound so it is presumed not to be genotoxic [ 28 , 29 ]. It is important to emphasize that not only CoQ 10 toxicity aspects should be evaluated when new and promising formulations are developed, but it is also fundamental to assess the possible interactions between the CoQ 10 and the other excipients contained in the formulae which could represent a toxic risk.…”