Physical exercise contributes to cisplatin-induced nephrotoxicity protection with decreased CD4+T cells activation

Author(s):Show less -

Saito Miyagi, Mariana Yasue ^[1] ; Latancia, Marcela Teatin ^{[1, 2]} ; Testagrossa, Leonardo Abreu ^[3] ; de Andrade-Oliveira, Vinicius ^[1] ; Pereira, Welbert Oliveira ^[4] ; Hiyane, Meire Ioshie ^[1] ; Enjiu, Lucas Maceratesi ^[5] ; Pisciottano, Marcus ^[5] ; Leite Seelaender, Marilia Cerqueira ^[5] ; Saraiva Camara, Niels Olsen ^{[1, 6]} ; Amano, Mariane Tami ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Immunobiol Transplants, Sao Paulo, SP - Brazil

^[2] Hosp Sirio Libanes, Inst Sirio Libanes Ensino & Pesquisa, Rua Daher Cutait, 69 7SS Bloco D, BR-01308060 Sao Paulo, SP - Brazil

^[3] Hosp Sirio Libanes, Clin Pathol Lab, Sao Paulo, SP - Brazil

^[4] Hosp Israelita Albert Einstein, Fac Israelita Ciencias Saude Albert Einstein, Sch Med, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Cell Biol, Lab Lipid Metab, Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Fac Med, Lab Renal Pathol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Molecular Immunology; v. 101, p. 507-513, SEP 2018.
• Web of Science Citations: 0

Abstract

Cisplatin is a chemotherapy used to treat different types of cancer, such as testicular, bladder and head and neck. Physical exercise has been shown to improve cancer therapy and recently, it was demonstrated to be able to diminish side effects such as acute kidney injury (AKI), a common side effect in cisplatin treatment. In both cases, the modulation of inflammatory cytokines seems to be one of the mechanisms, but little is known about the immune cells in this process. Here, we investigated the role of CD4 + T cells in the AKI protection by physical exercise. We subjected C57B16 mice to long-term physical exercise (EX) before cisplatin treatment. Sedentary groups were used as control (CT). We confirmed that physical exercise decreased AKI by evaluating creatinine and Kim-1 levels, in the serum and kidney respectively. Analyzing the organs weight, we noticed a decrease in sedentary (CIS) and exercised (CIS-EX) cisplatin treated groups. Epididymal and brown adipose tissue weight were decreased in cisplatin treated subjects in comparison to untreated groups, as well as liver and spleen. We then investigated the profile of CD4 + T cells in the spleen and we observed increased levels of Tregs and CD4 + CD25 + cells in CIS group, while CIS-EX presented similar amounts as control groups. Analyzing the kidney lymph nodes, we noticed a decrease of CD4 + cells in both CIS and CIS-EX group. However, a more activated phenotype (CD69 + and CD25 + ) was observed in CIS groups in comparison to CIS-EX group, as well as the presence of Tregs. We then investigated the production of cytokines by these cells and no difference among the groups was observed in cytokines production in splenic CD4 + T cells. However, a clear increase in TNF and IL-10 production was observed in CD4 + T cells from lymph nodes, while CIS-EX group presented similar levels as the control groups. We confirmed that physical exercise was able to diminish cisplatin-induced AKI with concomitant decrease in CD4 + T cell activation. (AU)

• FAPESP's process: 12/50079-0 - Systemic inflammation in cachectic cancer patients: mechanisms and therapeutical strategies, a translational medicine approach
• Grantee: Marilia Cerqueira Leite Seelaender
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/10349-5 - The role of the physical exercise in renal injury induced by cisplatin
• Grantee: Mariana Yasue Saito Miyagi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/10435-1 - THE INFLUENCE OF MTOR PATHWAY IN MACROPHAGE MODULATION AND ITS CONSEQUENCES IN EXPERIMENTAL CHRONIC KIDNEY DISEASE
• Grantee: Mariane Tami Amano
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants