Cerium Oxide Nanoparticles Attenuate Diabetic Nephropathy in Rats by Reducing Oxidative Stress, Improving Dyslipidemia, and Modulating PKM2 and KIM-1

Jamal  Amri; Abolfazl  Emadi; Narjes  Rezaei; Zahra  Salemi

doi:10.18502/abi.v2i4.19107

Jamal Amri Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abolfazl Emadi Department of Clinical Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tehran, Iran
Narjes Rezaei Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran
Zahra Salemi Department of Biochemistry and Genetic, Arak University of Medical Sciences, Arak, Iran

DOI: https://doi.org/10.18502/abi.v2i4.19107

Keywords: Diabetic Nephropathy, Cerium Oxide Nanoparticles, Oxidative Stress, PKM2 , KIM-1

Abstract

Objectives: Oxidative stress and inflammation play important roles in the pathophysiology of diabetic nephropathy (DN). Nanoparticles, including cerium oxide nanoparticles (CeO₂NPs), which reduce oxidative stress and inflammation, are increasingly utilized in disease treatment. This study aims to assess the preventive potential of CeO₂NPs in a DN animal model by examining their effects on glucose levels, lipid profiles, oxidative stress, and kidney damage markers.

Methods: Diabetes was induced in rats using streptozotocin (STZ). Rats were divided into three groups: normal control (N-Cnt), diabetic control (D-Cnt), and CeO₂NP- treated (D-CeO₂, 60 mg/kg) groups. Fasting blood glucose (FBG) levels were measured at baseline and on day 35. Additionally, serum lipid profiles (total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)) were assessed. In kidney tissue, activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), levels of malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as mRNA expression of pyruvate kinase M2 (PKM2 ) and kidney injury molecule-1 (KIM-1) were analyzed.

Results: CeO₂NP treatment in D-CeO₂ rats significantly reduced FBG and improved lipid profiles (decreased TC, TG, LDL-C; increased HDL-C, P < 0.05). CeO₂NPs also attenuated oxidative stress (increased SOD, CAT, GPx, TAC; reduced MDA, P < 0.05) and downregulated PKM2 and KIM-1 mRNA expression (P < 0.05) compared to D-Cnt rats.

Conclusion: CeO₂NPs demonstrate protective effects against DN in this rat model by ameliorating hyperglycemia, dyslipidemia, oxidative stress, and renal injury marker expression. These findings suggest that CeO₂NPs may possess therapeutic potential for DN, warranting further investigation into their mechanisms and clinical applicability.