Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity.

Reproductive toxicology (Elmsford, N.Y.) 2020 Apr

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Kallikrein-kinin system (KKS) is involved in vascular reactivity and inflammatory response to cytotoxic drugs. Since cisplatin is a widely used chemotherapy and its cytotoxic mechanism can trigger inflammation and oxidative damage, in this work we evaluated the role of KKS in an animal model of cisplatin-induced ovarian toxicity. Biomarkers of ovarian stem cells, activity of KKS, inflammation and oxidative damage were measured in ovarian tissue of C57BL/6 female mice treated with vehicle or cisplatin (2.5 mg/kg). Cisplatin group presented greater number of atretic follicles, and lower numbers of antral and total viable follicles. Ki67, DDX4 and OCT-4 markers were similar between groups. Cisplatin triggered plasma and ovarian tissue kallikrein generation; and increased expression of bradykinin receptors B1 and B2. Neutrophil and macrophage infiltration markers increased. Superoxide anion generation also increased, while reduced glutathione levels decreased. These results suggest that KKS is activated and contributes to ovarian injury during cisplatin treatment. Copyright © 2019 Elsevier Inc. All rights reserved.

Citation

Laura Silveira Ayres, Markus Berger, Isabel Cirne Lima de Oliveira Durli, Cristiana Palma Kuhl, Paula Barros Terraciano, Tuane Nerissa Alves Garcez, Bruna Gomes Dos Santos, Jorge Almeida Guimarães, Eduardo Pandolfi Passos, Elizabeth Obino Cirne-Lima. Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity. Reproductive toxicology (Elmsford, N.Y.). 2020 Apr;93:1-9