Sinapic Acid Attenuated Cisplatin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and İnflammation with GPX4-Mediated NF-kB Modulation.

Yildirim, Caner; Cangi, Sibel; Orkmez, Mustafa; Yilmaz, Senay Gorucu; Bozdayı, Mehmet Akif; Yamaner, Hatice; Cevik, Sena

The use of cisplatin is severely limited by the risk of developing cardiovascular complications. Sinapic acid may reduce cisplatin's side effects. The anti oxidant, anti-inflammatory, and peroxynitrite-scavenging properties of sinapic acid could provide protection against the cardiotoxicity caused by cisplatin. To induce toxicity in rats, cisplatin was administered for a period of 5 weeks. Animal electrocardiograms were obtained after cisplatin toxicity had taken effect. Blood samples and heart tissues were then harvested from the anesthetized animals. The ELISA technique was used to evaluate the level of proinflammatory cytokines and oxidative and nitrosative stress indicators in the heart tissue and serum. A real-time PCR was used to analyze GPX4 and NF-κB expression in the heart tissue. Hematoxylin–eosin and Masson's trichrome were also utilized. Electrocardiograms data showed an increase in QRS and QT intervals. Biochemically, cisplatin increased oxidative, nitrosative, and proinflammatory cytokine levels. Animals exposed to cisplatin had histopathological findings in the heart tissue, according to the results of histological assessment. Sinapic acid reduced TNF-alpha, interleukin-6, malondialdehyde, and ischemia-modified albumin. Sinapic acid also reduced oxidative and nitrosative stress. Furthermore, Sinapic acid restored lengthy QT and QRS. Cisplatin-treated rats had higher NF-κB activation than controls. This effect was successfully inhibited by sinapic acid. Histopathologically, tissues treated with sinapic acid were less damaged than tissues treated with cisplatin. In conclusion, our results suggest that sinapic acid exhibited a protective effect against the cardiotoxicity induced by cisplatin. These effects may be caused by the overexpression of GPX4 and the downregulation of NF-KB, as well as antioxidant and anti-inflammatory properties.

CISPLATIN; OXIDATIVE stress; CARDIOTOXICITY; STAINS & staining (Microscopy); NF-kappa B; CARDIOLOGICAL manifestations of general diseases

Cardiovascular Toxicology, 2023, Vol 23, Issue 1, p10

1530-7905

Academic Journal

10.1007/s12012-022-09773-3