Hepcidin Peptide Inhibitor As Cardioprotection by Targeting Oxidative Stress and Inflammation in Type 1 Diabetic Publisher



Zeinivand M^{1, 2} ; Nahavandi A^{1, 3} ; Baluchnejadmojarad T¹ ; Roghani M⁴ ; Golab F⁵ Show Affiliations
Source: International Journal of Peptide Research and Therapeutics Published:2020

Abstract

Hepcidin peptide is the dominant regulator of systemic iron metabolism. Studies suggest a dual role of hepcidin in neuronal iron load and inflammation. This is vital since iron load and inflammation are pathophysiological processes, which are frequently associated with diabetic cardiomyopathy. Furthermore, manipulation of hepcidin activity has recently been used to recover heart damage due to inflammation in type 1 diabetic animal models. In order to induce type 1 diabetic model, streptozotocin (STZ) was used. Animals were divided into groups of control (C), diabetic (D), diabetic + iron (ID), and diabetic + dalteparin (DD). Then, 100 mg/kg of dalteparin (anti-hepcidin) was administered intraperitoneally, and 12 mg/kg of iron administration P.O in rats once a day after diabetes for 8 weeks. At the end of the experiment, animals were perfused and their heart tissue was prepared to measure serum iron level, ferritin, inflammatory cytokines such as IL-6, serum C-reactive protein (CRP), oxidative stress markers such as membrane lipid peroxidation (MDA), and hepcidin peptide gene expression. After inhibiting hepcidin by dalteparin treatment, serum levels of IL-6, CRP, glucose levels, iron and tissue levels of MDA and ferritin were remarkably reduced (p < 0.05). Likewise, inhibiting hepcidin peptide improved cardiac complications 8 weeks after induced type 1 diabetic (p < 0.05). Manipulation of hepcidin peptide by dalteparin could ameliorate diabetic cardiomyopathy (DM) in streptozotocin-diabetic rats through appropriate modulation and mitigation of oxidative stress and inflammation and this may expand the existing library of therapeutics to lower the complications of diabetes. © 2019, Springer Nature B.V.