Changes in CoQ10/Lipids Ratio, Oxidative Stress, and Coenzyme Q10 during First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma (mUC)

Int J Mol Sci. 2022 Oct 28;23(21):13123. doi: 10.3390/ijms232113123.

Abstract

Oxidative stress plays an important role in cancer pathogenesis, and thiobarbituric acid-reactive substance level (TBARS)—a parameter of lipid peroxidation—has prognostic significance in chemotherapy-naive patients with metastatic urothelial carcinoma (mUC). However, the effect of cisplatin (CDDP)-based chemotherapy on oxidative stress, coenzyme Q10, and antioxidants remains unknown. The objective of this prospective study was to determine possible changes in the CoQ10 (coenzyme Q10)/lipids ratio, antioxidants (α-tocopherol, γ-tocopherol, β-carotene, CoQ10), total antioxidant status (TAS), and TBARS in plasma at baseline and during first-line chemotherapy based on CDDP in mUC subjects. In this prospective study, 63 consecutive patients were enrolled. The median age was 66 years (range 39−84), performance status according to the Eastern Cooperative Oncology Group (ECOG) was 2 in 7 subjects (11.1%), and visceral metastases were present in 31 (49.2%) patients. Plasma antioxidants were determined by HPLC and TAS and TBARS spectrophotometrically. After two courses of chemotherapy, we recorded significant enhancements compared to baseline for total cholesterol (p < 0.0216), very low-density lipoprotein (VLDL) cholesterol (p < 0.002), triacylglycerols (p < 0.0083), α-tocopherol (p < 0.0044), and coenzyme Q10-TOTAL (p < 0.0001). Ratios of CoQ10/total cholesterol, CoQ10/HDL-cholesterol, and CoQ10/LDL-cholesterol increased during chemotherapy vs. baseline (p < 0.0048, p < 0.0101, p < 0.0032, respectively), while plasma TBARS declined (p < 0.0004). The stimulation of antioxidants could be part of the defense mechanism during CDDP treatment. The increased index of CoQ10-TOTAL/lipids could reflect the effect of CDDP protecting lipoproteins from peroxidation.

Keywords: cisplatin; coenzyme Q10/lipids ratio; metastatic urothelial carcinoma; thiobarbituric acid-reactive substances; α-tocopherol.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antioxidants / pharmacology
  • Carcinoma, Transitional Cell*
  • Cholesterol, HDL
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Humans
  • Middle Aged
  • Oxidative Stress
  • Prospective Studies
  • Thiobarbituric Acid Reactive Substances
  • Triglycerides / pharmacology
  • Ubiquinone / pharmacology
  • Urinary Bladder Neoplasms*
  • alpha-Tocopherol / pharmacology

Substances

  • Ubiquinone
  • Antioxidants
  • Cisplatin
  • Thiobarbituric Acid Reactive Substances
  • alpha-Tocopherol
  • Triglycerides
  • Cholesterol, HDL

Grants and funding

This study was supported by Scientific Grant—Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences: VEGA 1/0614/12, and OncoReSearch, Slovakia (Article Processing Charge, APC). The funding bodies had no role in the writing of this manuscript.