Metrnl impact in streptozotocin induced diabetic nephropathy in rats, targeting Nrf2/HO-1 pathway

Introduction: The most prevalent complications in diabetes mellitus is diabetic nephropathy (DN). Metrnl's role in endocrine metabolism has been well investigated. It has been demonstrated to contribute to the healing of inflammatory injury.Objective: to assess the potential underlying processes and the protective impact of Metrnl in DN caused by STZMaterials and Methods: Thirty adult male albino rats were split into: control, DN, and DN+Metrnl (10/group). Urine albumin, serum glucose, serum glycosylated Hb A1c, serum urea, serum creatinine, serum cystatin C, creatinine clearance, renal MDA, renal GSH, renal TNF-α, renal IL-10, and renal gene expression of HO-1 and Nrf2 were assessed. Additionally, immunohistochemical and renal histopathology studies were carried out.Results The DN group had significantly higher serum levels of glucose, glycosylated Hb A1c, urea, creatinine, cystatin C, urinary albumin, renal MDA, and renal TNF-α than the control group, but they also had significantly lower renal GSH, renal IL-10, creatinine clearance values, and Nrf2 and HO-1 gene expression. Furthermore, NF-kB and Bax immunoreaction were upregulated in the DN compared to control. The STZ-induced DN alterations significantly improved in the DN+Metrnl group.Conclusion: Metrnl offers substantial protection against STZ-induced DN through anti-oxidant and anti-inflammatory pathways, apoptosis inhibition, and the up-regulation of Nrf2 and HO-1 renal gene expressions.