Protective Potential of Humanin in Renal Ischemia/Reperfusion Injury in Rats: Unveiling Mitochondria-Targeted Mechanisms | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Volume 45, Issue 4, October 2025, Pages 429-448 PDF (1.28 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2025.369621.1208 | ||
| Authors | ||
| Islam Ibrahim Hegab* 1; asmaa hamdy okasha2; Alaa Abd El-Azeem3; Maram Ghabrial4; eman basha1; Amira Abdel maged5; Hanan Abdallah6 | ||
| 1Medical Physiology Department, Faculty of Medicine, Tanta University , Tanta, Egypt. | ||
| 2medical biochemistry & molecular biology department, Faculty of Medicine, Tanta University, Egypt. | ||
| 3Medical Pharmacology Department, Faculty of Medicine, Tanta University , Tanta, Egypt. | ||
| 4Anatomy & Embryology Department, Faculty of Medicine, Tanta University , Tanta, Egypt. | ||
| 5Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt. | ||
| 6Faculty of Medicine, Tanta University, Tanta, Egypty of Medicine, Tanta University, Tanta, Egypt | ||
| Abstract | ||
| Background: Renal ischemia-reperfusion injury (IRI) is an intricate clinical pathophysiological phenomenon in which oxidative stress, apoptosis, and mitochondrial dysfunction play crucial roles. Aim: Validating the effect of humanin (HN) on kidney function in a renal IRI rat model, using its synthetic analogue, S14G-humanin (HNG). Methodology: Forty male Wistar rats were categorized into sham, HNG, IR, and IR-HNG groups. Renal function and histopathological analysis were valued to estimate the pathological renal injury. Mitochondrial function was judged by measuring ATP production, mitochondrial transmembrane potential (ΔΨm), the electron transport chain (ETC) enzyme complex-I activity, and mitochondrial mitophagy-related genes of Drp1 and Mfn2. Redox, inflammation, and apoptosis biomarkers were scrutinized. The renal PGC-1α, PI3K, AKT, and HIF-1α, coupled with P-JAK2, and P-STAT 3 were evaluated. Bcl-2 and SIRT1 immunoreactivity were assessed. Results: Our findings elucidated that HNG’s reno-protective potential against IR-elicited renal damage and mitochondrial dysfunction is mostly mediated via activating the renal SIRT1 / PGC-1α, PI3K/AKT/ HIF-1α, and JAK2/STAT3 signaling. By targeting these crucial pathways, HNG could dampen the renal IR-provoked oxidative stress, inflammation, and apoptosis, and enhance mitochondrial mitophagy and biogenesis. Accordingly, HNG could be a promising therapeutic candidate for renal pathology allied with IRI. | ||
| Keywords | ||
| Humanin; renal ischemia/reperfusion injury; mitochondrial dysfunction | ||
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