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Punicalagin protects against the development of pancreatic injury and insulitis in rats with induced T1DM by reducing inflammation and oxidative stress

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Abstract

Pancreatic inflammation and oxidative damage remain major concerns in type 1 diabetes mellitus (T1DM). Punicalagin, a major polyphenol in pomegranates, exhibited antioxidant and protective effects on several organs in case of T1DM; however, no study has yet explored the protective effects of punicalagin on the pancreas and islets of Langerhans. T1DM was induced by injecting 40 mg/kg streptozotocin (STZ) intraperitoneally. Punicalagin (1 mg/kg ip) was injected daily for 15 days after T1DM induction. In diabetic rats, punicalagin treatment lowered the levels of inflammatory biomarkers (monocyte chemoattractant protein-1 and C-reactive protein) and adhesion molecules (E-selectin, intercellular adhesion molecule, and vascular cell adhesion molecule) while activating myeloperoxidase activity. Treatment of diabetic rats with punicalagin improved glutathione content and superoxide dismutase, catalase, and glutathione peroxidase activities; upregulated serum paraoxonase-1 activity; and prevented the elevation lipid peroxidation and protein oxidation products in the pancreas. Furthermore, punicalagin protected the pancreas against STZ-induced histopathological alterations and increased immune-reactive β-cells while reducing leucocyte infiltration into the islets of Langerhans, leading to normalized blood glucose and insulin levels. These findings indicated that punicalagin might protect against the development of insulitis in T1DM. In conclusion, punicalagin exerts a strong protective effect on the pancreas against oxidative injury and inflammation in STZ-induced experimental T1DM. The present results recommend punicalagin as a potential adjuvant for reducing diabetes-associated insulitis.

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Acknowledgements

Facilities provided by Mansoura University are greatly acknowledged.

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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Biology Department, College of Education for Pure Sciences, University of Anbar, Anbar, Ramadi, Iraq

    Haitham L. Abdulhadi & Loay H. Ali

  2. Biology Department, College of Education for Pure Sciences, University of Mosul, Mosul, Iraq

    Banan R. Dabdoub

  3. Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt

    Azza I. Othman, Maggie E. Amer & Mohamed A. El-Missiry

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  1. Haitham L. Abdulhadi
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  2. Banan R. Dabdoub
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by HLA, BRD, LHA, AIO, MAEM, and MEA. The first draft of the manuscript was written and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Maggie E. Amer or Mohamed A. El-Missiry.

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All procedures performed in this study were conducted in accordance with the regulations approved by the Ethics Committee at Faculty of Science, Mansoura University, Egypt.

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Abdulhadi, H.L., Dabdoub, B.R., Ali, L.H. et al. Punicalagin protects against the development of pancreatic injury and insulitis in rats with induced T1DM by reducing inflammation and oxidative stress. Mol Cell Biochem 477, 2817–2828 (2022). https://doi.org/10.1007/s11010-022-04478-1

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