Document Type : Original Article
Authors
1
Medical Physiology Department, Faculty of Medicine, Tanta University , Tanta, Egypt.
2
medical biochemistry & molecular biology department, Faculty of Medicine, Tanta University, Egypt.
3
Medical Pharmacology Department, Faculty of Medicine, Tanta University , Tanta, Egypt.
4
Anatomy & Embryology Department, Faculty of Medicine, Tanta University , Tanta, Egypt.
5
Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt.
6
Faculty 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.
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