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Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity – possible modulatory role of IL-11

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Abstract

Apoptotic signaling pathways are involved in acute kidney injury (AKI) induced by the antineoplastic drug cisplatin (Cis). Mechanical stress is known to increase interleukin (IL) -11, a pleiotropic cytokine with antiapoptotic and antinecrotic effects. We compared the impact of high-intensity interval training (HIIT) with low-intensity continuous training (LICT) and moderate-intensity continuous training (MICT) on renal levels of IL-11 and the expression of apoptotic markers in female rats with nephrotoxicity induced by Cis. For that, the animals were divided into five groups (n = 7): control and sedentary (C + S); Cis and sedentary (Cis + S); Cis and LICT (Cis + LICT); Cis and MICT (Cis + MICT) and Cis and HIIT (Cis + HIIT). At the end of 8 weeks of treadmill running, the rats received a single injection of Cis (5 mg/kg), and 7 days later they were euthanized. Serum and kidney samples were collected to assess the blood urea nitrogen (BUN), gene expression of TNF receptor 1 (TNFR1) and 2 (TNFR2), caspase-3, (p38) MAPK (MAPK14), p53, Bax, Bak, Bcl-2, and Bcl-xL, renal levels of IL-11, IL-8, and p53, and immunolocalization of cleaved caspase-3, Bax, Bcl-2, and (p38) MAPK in renal tissue. Our data indicate that all trained groups showed a significant intensity-dependent increase in renal levels of IL-11 associated with reduced local expression of proapoptotic and increased antiapoptotic markers, but these effects were more pronounced with HIIT. So, HIIT appears to provide superior renoprotection than traditional continuous training by modulating apoptotic signaling pathways, and this effect can be related to the increase in renal levels of IL-11.

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Data availability

the datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

authors are grateful to professor Regiane Yatsuda for donating experimental animals, and Luiza Brito Amaral for her artistic contribution.

Funding

this work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant number: 433542/2018-7, and Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB), grant number: 1144/2021.

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  1. Instituto Multidisciplinar em Saúde, Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal da Bahia, Vitória da Conquista, Rua Rio de Contas, 58, Candeias, 45029-094, Bahia, Brazil

    Caroline Assunção Oliveira, Érika Azenathe Barros Mercês, Fernanda Santos Portela, Júlia Mafra De Benedictis¹, Laís Mafra De Benedictis, Antônio Victor Brito da Silva, João de Assis Gonçalves Campanati, Fabrício Freire de Melo, Márcio Vasconcelos Oliveira, Amélia Cristina Mendes de Magalhães, Telma de Jesus Soares & Liliany Souza de Brito Amaral

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  1. Caroline Assunção Oliveira
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Contributions

LSBA designed the study, supervised, and coordinated the project. LSBA and CAO wrote the original manuscript. LSBA, CAO, TJS, and FFM revised the paper. CAO, JMB, LMB, AVBS, and JAGC conducted animal experiments. CAO, EABM, FSP, FFM, and MVO conducted laboratory experiments. LSBA, ACMM, and TJS discussed the results and analyzed the data. All authors read and approved this manuscript.

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Correspondence to Liliany Souza de Brito Amaral.

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the Ethics Committee on Animal Experimentation of the Federal University of Bahia - Multidisciplinary Institute of Health approved this experimental protocol (056/2018), and all experimental procedures were conducted in accordance with the recommendations of the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Oliveira, C.A., Mercês, É.A.B., Portela, F.S. et al. Benefits of high-intensity interval training compared to continuous training to reduce apoptotic markers in female rats with cisplatin nephrotoxicity – possible modulatory role of IL-11. Apoptosis 28, 566–575 (2023). https://doi.org/10.1007/s10495-023-01816-6

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