Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

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

(2019) The effects of Hemiscorpius lepturus induced-acute kidney injury on PGC-1alpha gene expression: From induction to suppression in mice. Toxicon. pp. 57-63. ISSN 0041-0101

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/31887316

Abstract

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-1alpha. 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-AKI in modulating mitochondrial function in cell death and metabolic signaling associated with PPAR-alpha, PGC-1alpha, 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-1alpha and Nrf-2 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-1alpha upregulation occurs after AKI. As the findings indicate, PGC-1alpha has a key role in restoring the mitochondrial function at the recovery phase of mouse model of AKI, which highlights the PGC-1alpha as a therapeutic target for venom induced-AKI prevention and treatment.

Item Type: Article
Keywords: Bax/ Bcl-2,Heme oxygenase-1,Hemiscorpius lepturus,Nrf-2,PGC-1alpha,PPAR-alpha
Subjects: WJ Urogenital System > WJ 300-378 Kidney
Divisions: Education Vice-Chancellor Department > Faculty of Pharmacy > Department of Toxicology and Pharmacology
Page Range: pp. 57-63
Journal or Publication Title: Toxicon
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q3
Volume: 174
Publisher: Elsevier
Identification Number: https://doi.org/10.1016/j.toxicon.2019.12.154
ISSN: 0041-0101
ISBN: 0041-0101
Depositing User: خانم فائزه مظفری
URI: http://repository.zums.ac.ir/id/eprint/5726

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