The role of annexin A1-derived peptide Ac2-26 on liver and kidney injuries induced by cisplatin in rats

Author(s)

Lucchi, Danilo B. M. ; Sasso, Gisela R. S. ; Sena, Leticia S. ; Santos, Diego D. ; Franco, Paulo C. ; Lice, Izabella ; Borges, Fernanda T. ; Oliani, Sonia M. ; Gil, Cristiane D.

• Document type: Journal article
• Source: Life Sciences; v. 304, p. 10-pg., 2022-09-01.

Abstract

Aims: In this study we evaluated the effect of pharmacological treatment with AnxA1-derived peptide Ac2-26 in an experimental model of toxicity induced by cisplatin. Main methods: Male rats were divided into Sham (control), Cisplatin (received intraperitoneal injections of 10 mg/kg/day of cisplatin for 3 days) and Ac2-26 (received intraperitoneal injections of 1 mg/kg/day of peptide, 15 min before cisplatin) groups. Key findings: After 6 h of the last dose of cisplatin, an acute inflammatory response was observed characterized by a marked increase in the number of neutrophils and GM-CSF, IL-beta, IL-6, IL-10 and TNF-alpha plasma levels. These findings were associated with increased AnxA1 protein levels in liver and kidneys, as well as positive AnxA1/Fpr2 circulating leukocytes. Treatment with Ac2-26 produced higher levels of GM-CSF, corroborating the high numbers of neutrophils, and the anti-inflammatory cytokine IL-4. Ac-2-(26) preserved the morphology of liver structures and increased Fpr1 expression, preventing the damage caused by cisplatin. In the kidneys, Ac2-26 caused downregulation of renal Fpr1 and Fpr2 levels and abrogated the increased levels of the CLU and KIM-1 biomarkers of kidney damage induced by cisplatin. However, no effect of peptide treatment was detected in cisplatin-induced kidney morphology injury. Significance: Despite activation of the anti-inflammatory AnxA1/Fpr axis during cisplatin administration, treatment with Ac2-26 did not efficiently prevent its deleterious effects on the liver and kidneys. (AU)

• FAPESP's process: 19/14331-5 - Effect of annexin A1 mimetic peptide on hepatic and renal toxicity induced by cisplatin in rats
• Grantee: Danilo Bancalero Mendonça Lucchi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 19/19949-7 - Evaluation of annexin A1 protein immunomodulatory activity in cutaneous and placental lesions resulting from Diabetes Mellitus
• Grantee: Sonia Maria Oliani
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/03565-2 - Effect of annexin A1 and its mimetic peptides in models of inflammatory response in vitro (2D and 3D) and acute toxicity in vivo
• Grantee: Cristiane Damas Gil
• Support Opportunities: Regular Research Grants