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The impact of apelin-13 on cisplatin-induced endocrine pancreas damage in rats: an in vivo study

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Apelin-13 is a peptide hormone that regulates pancreatic endocrine functions, and its benefits on the endocrine pancreas are of interest. This study aims to investigate the potential protective effects of apelin-13 in cisplatin-induced endocrine pancreatic damage. Twenty-four rats were divided into four groups: control, apelin-13, cisplatin, and cisplatin + apelin-13. Caspase-3, TUNEL, and Ki-67 immunohistochemical staining were used as markers of apoptosis and mitosis. NF-κB/p65 and TNFα were used to show inflammation. β-cells and α-cells were also evaluated with insulin and glucagon staining in the microscopic examination. Pancreatic tissue was subjected to biochemical analyses of glutathione (GSH) and malondialdehyde (MDA). Apelin-13 ameliorated cisplatin-induced damage in the islets of Langerhans. The immunopositivity of apelin-13 on β-cells and α-cells was found to be increased compared to the cisplatin group (p = 0.001, p = 0.001). Mitosis and apoptosis were significantly higher in the cisplatin group (p = 0.001). Apelin-13 reduced TNFα, NF-κB/p65 positivity, and apoptosis caused by cisplatin (p = 0.001, p = 0.001, p = 0.001). While cisplatin caused a significant increase in MDA levels (p = 0.001), apelin caused a significant decrease in MDA levels (p = 0.001). The results demonstrated a significant decrease in pancreatic tissue GSH levels following cisplatin treatment (p = 0.001). Nevertheless, apelin-13 significantly enhanced cisplatin-induced GSH reduction (p = 0.001). On the other hand, the serum glucose level, which was measured as 18.7 ± 2.5 mmol/L in the cisplatin group, decreased to 13.8 ± 0.7 mmol/L in the cisplatin + apelin-13 group (p = 0.001). The study shows that apelin-13 ameliorated cisplatin-induced endocrine pancreas damage by reducing oxidative stress and preventing apoptosis.

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SC: Formal Analysis, Investigation, Writing an original draft. LT: Conceptualization, Methodology, Investigation, Data curation, Writing-original draft. TM: Methodology, Software, Investigation, Writing an original draft, Writing-review, and editing. SS: Conceptualization, Methodology, Investigation. KA and AY: Methodology, Writing-review, and editing, FM: Methodology, Investigation, Writing an original draft.

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Correspondence to Filiz Mercantepe.

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The authors declare that there is no conflict of interest.

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The study was conducted according to the ethical standards specified in the 1964 Declaration of Helsinki. Research and publication ethical rules were followed in our study. Our study was approved by the ethics committee of Recep Tayyip Erdogan University Animal Experiments Ethical Committee (Rize, Turkiye, Approval number 2022/31, Approval date 29/07/2022).

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The present study is an animal study; no informed consent is required.

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Ciftel, S., Tumkaya, L., Saral, S. et al. The impact of apelin-13 on cisplatin-induced endocrine pancreas damage in rats: an in vivo study. Histochem Cell Biol 161, 391–408 (2024).

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