title: The effects of coenzyme Q10 and baicalin in cisplatin-induced lipid peroxidation and nitrosative stress.
abstract: Cisplatin is the alkylating anticancer drug. These drugs show many side-effects including the damage of kidney. The nephrotoxicity of cisplatin is explained mainly by reactive oxygen species (ROS) generation. The increased level of lipids peroxidation was observed in patients treated with this drug. In the toxicity of cisplatin, are also involved reactive nitrogen species (RNS) such as nitric oxide (NO*) or peroxynitrite. The lack of cisplatin selectivity and its side effects tend to look for ways to reduce the toxicity in chemotherapy. Our previous studies demonstrated that oxidative stress caused by xenobiotics can sometimes be effectively inhibited by coenzyme Q10 and baicalin. The aim of our research was the evaluation of usefulness of two coenzyme Q10 forms: lipophilic, currently used (QA) and new, produced by nanotechnology, soluble in water, PureSorb-QTM40-P40 (QB). Also the utility of baicalin as free radicals scavenger in reducing the nephrotoxicity of cisplatin was examined. The study was performed on an in vitro model, human erythrocytes and serum. Oxidative stress was evaluated by the level of lipid peroxidation (TBARS method). The concentration of nitric oxide (NO*) and nitrate (NO3) was estimated in serum [Nitric Oxide Colorimetric Detection Kit (Cat. No. K023-H1) of Arbor Assays], based on reaction with Griess reagent. Cisplatin at concentration: 3.5, 10, 30 and 50 pg/mL significantly increased the level of TBARS in erythrocytes. All antioxidants: baicalin and two forms of coenzyme Q10 significantly inhibited TBARS compared to controls (p < 0.05). Both QA and QB studied in a wide range of concentrations (from 1.0 to 120.0 microg/mL) demonstrated their antioxidative effect. In all used doses they statistically significantly decreased TBARS level with the negative correlation (r = -0.751; p = 0.000). In the study of nitrosative stress, all doses of cisplatin increased NO* and NO3 level in serum (p < 0.05). Baicalin and QA showed no statistically significant influence on production of NO* and NO3 in serum, while QB unexpectedly increased these parameters. In joint exposure with cisplatin all three antioxidants, in the most of concentrations, decreased TBARS levels, elevated by cisplatin (p < 0.05). In nitrosative stress-induced by cisplatin, the most effective was QB, however, protective influence of all antioxidants varies and the results are ambiguous.
authors.affiliation: Department of Toxicology, Wroclaw Medical University, Borowska St. 211, 50-556 Wrocław, Poland. ewa.sawicka@umed.wroc.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Sawicka
authors.affiliation: Department of Toxicology, Wroclaw Medical University, Borowska St. 211, 50-556 Wrocław, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Długosz
authors.affiliation: Department of Toxicology, Wroclaw Medical University, Borowska St. 211, 50-556 Wrocław, Poland.
authors.forename: Krzysztof P
authors.initials: KP
authors.lastname: Rembacz
authors.affiliation: Department of Toxicology, Wroclaw Medical University, Borowska St. 211, 50-556 Wrocław, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Guzik
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D026361:Reactive Nitrogen Species / Q000097:blood*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D005419:Flavonoids; D009566:Nitrates; D026361:Reactive Nitrogen Species; D017392:Thiobarbituric Acid Reactive Substances; D014451:Ubiquinone; D009569:Nitric Oxide; C038044:baicalin; C024989:coenzyme Q10; D002945:Cisplatin