Atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative damage and apoptosis induced by ovarian ischaemia/reperfusion injury

Redox Rep. 2022 Dec;27(1):212-220. doi: 10.1080/13510002.2022.2129192.

Abstract

Background: Oxidative damage is critical in the pathogenesis of ovarian ischaemia/reperfusion (I/R) injury, and statins have been reported to exert antioxidant activity. However, the role of VCAM-1 and xanthine oxidase (XO)/uric acid (UA) in ovarian I/R injury is not known. Also, whether or not atorvastatin exerts antioxidant activity like other statins is unclear.

Objectives: This study investigated the involvement of VCAM-1 and XO/UA in ovarian I/R injury and the likely protective role of atorvastatin.

Methods: Forty female Wistar rats were randomized into sham-operated, ischaemia, ischaemia/reperfusion (I/R), ischaemia and atorvastatin, and I/R and atorvastatin.

Results: In comparison with the sham-operated group, atorvastatin blunted ischaemia and I/R-induced distortion of ovarian histoarchitecture and follicular degeneration. Also, atorvastatin alleviated ischaemia and I/R-induced rise in XO, UA, and malondialdehyde, which was accompanied by inhibition of ischaemia and I/R-induced reductions in reduced glutathione level, enzymatic antioxidant activities and increase in myeloperoxidase activity and TNF-α and IL-6 levels by atorvastatin treatment. Additionally, atorvastatin blocked ischaemia and I/R-induced increase in VCAM-1 expression, caspase 3 activity, 8-hydroxydeoxyguanosine level and ovarian DNA fragmentation index.

Conclusion: For the first time, this study revealed that atorvastatin-mediated downregulation of VCAM-1 and XO/UA/caspase 3 signaling averts oxidative injury, inflammation, and apoptosis induced by ovarian ischaemia/reperfusion injury.

Keywords: Adhesion molecules; folliculogenesis; inflammation‌; ischaemia/reperfusion; ovary; statins‌; torsion/detorsion; ‌oocyte.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Antioxidants / metabolism
  • Apoptosis
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use
  • Caspase 3 / metabolism
  • Down-Regulation
  • Female
  • Glutathione / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Interleukin-6
  • Ischemia / complications
  • Ischemia / drug therapy
  • Malondialdehyde / metabolism
  • Oxidative Stress
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury* / drug therapy
  • Tumor Necrosis Factor-alpha / metabolism
  • Uric Acid
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Xanthine Oxidase / metabolism

Substances

  • 8-Hydroxy-2'-Deoxyguanosine
  • Antioxidants
  • Atorvastatin
  • Caspase 3
  • Glutathione
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-6
  • Malondialdehyde
  • Peroxidase
  • Tumor Necrosis Factor-alpha
  • Uric Acid
  • Vascular Cell Adhesion Molecule-1
  • Xanthine Oxidase

Grants and funding

The study was funded by the Authors’ Financial Contributions.