Asprosin, a prospective biomarker for rhabdomyolysis-induced acute kidney damage in rats: involvement of PKA/TGF-β1/SMAD-3 signaling pathway

Khalil, Sama Salah; Abd El-Fatah, Samaa Salah; Fathy, Maha Abdelhamid; Elwany, N E.; Ahmad, Enssaf Ahmad; Mohamed, Noura Mostafa; Habib, Marwa A

doi:10.21608/zumj.2023.209146.2796

Asprosin, a prospective biomarker for rhabdomyolysis-induced acute kidney damage in rats: involvement of PKA/TGF-β1/SMAD-3 signaling pathway

Document Type : Original Article

Authors

¹ Medical Physiology Department, Faculty of Medicine, Zagazig University

² Assistant Professor, Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University

³ Medical physiology department-Faculty of medicine-Zagazig university

⁴ Lecturer, Clinical Pharmacology Department, Faculty of Medicine, Zagazig University

⁵ Lecturer, Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University

⁶ Medical biochemistry department-Faculty of medicine-Zagazig university

10.21608/zumj.2023.209146.2796

Abstract

Background: Rhabdomyolysis is a primary skeletal muscle disruption syndrome with circulatory leakage of its intracellular contents and is seriously complicated by acute kidney injury (AKI). Asprosin is a novel glucogenic adipokine expressed in several tissues, including the kidneys, and has been implicated in some renal disorders via many pathogenic mechanisms. Material & Methods: 32 rats were divided equally into the control group, the calcitriol-treated group, the glycerol-treated group, and the glycerol+calcitriol-treated group. Blood, urine, and renal tissue samples were collected for biochemical, histological, immunohistochemical, and gene investigations. Results: Rats given glycerol had elevated levels of asprosin, creatine kinase, creatinine, BUN, renal MDA, IL-6, caspase-3, and caspase-9, as well as PKA mRNA, TGF-β1, and SMAD-3. While creatinine clearance, renal SOD, and catalase were decreased. Marked histopathological changes imply sever renal injury, faint PAS-positive reaction, strong positive immunoreaction for iNOS and TGF-β were found. These changes were reversed in glycerol+calcitriol-treated rats. Asprosin positively correlated with MDA, IL-6, caspase-3, caspase-9, mRNA levels of PKA, TGF-β1and SMAD-3, while it negatively correlated with SOD, and catalase. Conclusion: Serum asprosin levels are increased in rhabdomyolysis-induced AKI and calcitriol protect against AKI via suppressing asprosin and its dependent PKA-TGF-β1-SMAD-3 signaling pathway.

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