Rana Dizaji
1,2 
, Ali Sharafi
2,3, Jalal Pourahmad
4, Saba Vatanpour
5, Hossein Dinmohammadi
6, Hossein Vatanpour
4, Mir-Jamal Hosseini
2,7* 1 Department of Food Safety and Hygiene, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran
2 Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran
3 Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
4 Departments of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Department of Biology, University of British Columbia, Vancouver, Canada
6 Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences , Zanjan, Iran
7 Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
Abstract
Introduction: Acute kidney injury (AKI) may have a negative effect on mitochondrial hemostasis and bioenergetics as well as coenzyme Q10 (CoQ10) content. PGC-1α, AMPK, sirtuin 1 (Sirt1), and Sirt3, as the key metabolic regulators under nutritional stress, stimulate energy production via mitochondrial biogenesis during AKI. However, no report is available on the relationship between CoQ10 level and nutrient sensors in the pathophysiology of AKI caused by Hemiscorpius lepturus scorpion envenomation.
Methods: Three doses of venoms (1, 5, and 10 mg/kg) were administered by subcutaneous (SC) injection to male albino mice. The animals were sacrificed 1 day or 7 days after administration of venom and their kidneys were collected to analyze gene expression involved in AKI, nutrient sensors, and apoptosis signaling activation by real-time polymerase chain reaction (PCR) and the measurement of CoQ10 level using the High-performance liquid chromatography (HPLC) method.
Results: The data indicated a significant decrease in CoQ10 level after the administration of venom in 5 and 10 mg/kg. In addition, 1 day after the treatment, a significant over-expression of Sirt1 (5 and 10 mg/kg) was observed compared with normal mice. Overexpression of Sirt3 occurred 1 day and 7 days after treatment only at the dose of 5.0 mg/kg of venom. Furthermore, over-expression of AMPK as an important mitochondrial energetic sensor happened 1 day and 7 days after the injection of venom (5 mg/kg) (P<0.01). The significant increase in the gene expression of caspase-9 and 3 after the injection of venom (5 and 10 mg/kg) confirmed the role of cell death signaling.
Conclusion: The venom-induced energy-sensing pathways have a key role in gene expression of PGC-1α, AMPK, Sirt3, and CoQ10 content after venom-induced AKI.