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

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.

Automated summary

In this study, the pharmacological treatment with AnxA1-derived peptide Ac2-26 was evaluated in an experimental model of cisplatin-induced toxicity. The results showed that Ac2-26 treatment could alleviate the inflammatory response induced by cisplatin and protect the liver and kidneys from cisplatin-induced damage. However, the peptide treatment had no significant effect on kidney morphology injury.