The effects of Hemiscorpius lepturus induced-acute kidney injury on PGC-1α gene expression: From induction to suppression in mice

Hemiscorpius lepturus envenomation induces acute kidney injury (AKI) through hemoglubinoria and mitochondrial dysfunction. Mitochondria supports ATP production to promote the regulation of fluid and electrolyte balance. Mitochondrial homeostasis in different metabolic environments can be adjusted by overexpression of PGC-1 alpha. High reactive oxygen species (ROS) production after H. lepturus envenomation and heme oxygenase-1 (HO-1) overexpression causes ATP depletion as well as mitochondrial homeostasis disruption, which lead to progression in renal diseases. The present study aims to evaluate the role of venom induced-AM in modulating mitochondrial function in cell death and metabolic signaling associated with PPAR-alpha, PGC-1 alpha, and Nrf-2 as the main transcription factors involved in metabolism. Based on the data, two significant events occurred after envenomation: reduction of gl glutathione level and overexpression of the cytoprotective enzyme HO-1. Apaoptosis induction is associated with a significant decrease in the transcription of PPAR-alpha, PGC-1 alpha and Nrf2 after administrating lethal dose of venom (10 mg/kg). Furthermore, at the lower doses of venom (1 and 5 mg/kg), with a significant recovery accompanied with PGC-1 alpha upregulation occurs after AKI. As the findings indicate, PGC-1 alpha has a key role in restoring the mitochondrial function at the recovery phase of mouse model of AM, which highlights the PGC-1 alpha as a therapeutic target for venom induced-AKI prevention and treatment.