ESPN 54th Annual Meeting

ESPN 2022


 
EFFECT OF ELAMIPRETIDE ON MITOCHONDRIAL FUNCTIONS IN MICE WITH OXALATE NEPHROPATHY
Ismail Dursun 1 Eylem Taşkın Güven 2 Celal Güven 3 Züleyha Doganyigit 4 Ecma Güvenilir 1 Mehmet Memiş 1 Serpil Taheri 1 Zuhal Hamurcu 1 Meryem Şentürk 5 Hamiyet Altuntaş 6

1- Erciyes University Genome and Stem Cell Center
2- Niğde Ömer Halis Demir University, Faculty of Medicine Department of Physiology
3- Niğde Ömer Halis Demir University, Faculty of Medicine Department of Biophysics
4- Bozok University, Faculty of Medicine, Department of Physiology
5- Erciyes University, Faculty of Veterinary, Department of Biochemistry
6- Erciyes University Faculty of Medicine, Department of Medical Biology
7- Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Nephrology
 
Introduction:

It has been shown that mitochondrial damage may play an important role in the emerge of the oxalate nephropathy (ON), and prevention of mitochondrial damage is thought to be one of the most important targeted therapies. The aims of this study are 1) To investigate the possibile role of mitochondrial damage in the development of ON in mice 2) To investigate whether mitochondrial targeting tetrapeptide (Elamipretide) treatment has a therapeutic effect on mitochondrial function in a mouse model of ON.

Material and methods:

 As Figure 1, 35 C57BL6 mice at 10-12-weeks of age were used (8 controls, 27 experimental groups). The study group was administered 200 mg / kg sodium oxalate intraperitoneally (IP) for 4 days. No application was made to the positive control group after the 5th day. Phosphate buffer saline was administered to the placebo group on days 0-9, and elamipretide at a dose of 7.5 mg / kg / day was administered via IP to the drug groups. The experiment was terminated on the 10th day and the mice were bled and their kidneys removed. Histopathological evaluation was made in the kidney tissue. The kidneys were homogenized and biochemical measurements (TAS, TOS, SOD) were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. Oxidaitve strest index (OSI) was calculated. This study supported by the Erciyes University Scientific Research Center (TDK-2019-9184).

Results:

 Histologically, oxalate caused apparent tubulointerstitial inflammation which was alleviated by elamipretide. Both mitocondrial and cytosolic oxidant capasity (TOS), OSI were increased and anti-oxidant capasity (TAS) were decreased in mice with ON and all were recovered with elamipretide (Figure 2a-d). We found oxalate resulted in decreased MMP and it was alleviated by elamipretide.

Conclusions:

 In this study, it has been shown that mitochondrial damage occurs in mice with ON and is alleviated by elamipretide. We think mitocondrial targeting treatment may be used to decrease oxidative stress related injury in kidney tissue in mice with ON.