ESPN 53rd Annual Meeting

ESPN 2021


 
EFFECT OF ELAMIPRETIDE (SS-31) ON INFLAMMASOM FORMATION IN MICE MODEL WITH OXALATE NEPHROPATHY
Ismail Dursun 1 Zuhal Hamurcu 1 Serpil Taheri 1 Esra Tufan 1 Ecmel Mehmetbeyoglu 1 Nesrin Delibas 1 Zuleyha Doganyigit 3 Aydin Alan 4 Yurdun Kuyucu 5 Sait Polat 5 Gokmen Zararsız 6 Hakan Poyrazoğlu 2

1- Betül-Ziya Eren Genome and Stem Cell Center, Erciyes University, Kayseri, Turkey.
2- Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Nephrology
3- Department of Histology-Embryology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
4- Department of Anatomy, Faculty of Veterinary Medicine, University of Erciyes, Kayseri, Turkey.
5- Çukurova University Faculty of Medicine, Histology and Embryology Department, Adana, 01330, Turkey
6- Erciyes University, Department of Biostatistics, Kayseri, Turkey.
7- Erciyes University, Faculty of Medicine, Department of Medical Biology, Kayseri, Turkey
 
Introduction:

Inflammaoma complex (NOD-like receptor protein 3 (NRLP), apoptosis-associated speck-like protein (ASC), inactive butchipase-1) is a part of the innate immune system has recently been shown as the responsible mechanisms that lead to kidney damage in kidney stone disease. According to the one of the mechanisms responsible for this process,  crystal structures such as oxalate enter the cell and cause mitochondrial damage. Then  reactive oxygen species resulting from the damage cause the formation of the inflammasome complex. Elamipretide is a drug containing peptide in aromatic cationic structure and it has been shown that acute tubular necrosis prevents the development of chronic damage in the kidneys by reducing the formation of inflammasome. In this study, it was investigated whether the use of Elamipretide for the first time reduced the activation of the inflammatory pathway caused by oxalate crystals and the occurrence of kidney damage

Material and methods:

In this study, 40 C57BL6 mice at 10-12-weeks of age were used (8 controls, 32 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 5 and 7.5 mg / kg / day was administered via IP to the drug groups. On days of 0,5 and 10, the mice were weighed and urinated. The experiment was terminated on the 10th day and the mice were bled and their kidneys removed. Serum kreatinine was measured. Histopathological evaluation was made in the kidney tissue. The mRNA expression levels of genes and proteins involved in the formation of the inflammasome complex were measured and protein levels were determined by western blot. This study supported by the Erciyes University Scientific Research Center (TOA-2018-7752)

Results:

When the mice were evaluated in terms of weight changes between the 0th and 5th days, weight gain was observed in the negative control group, while weight loss was detected in the other groups and the difference was statistically significant. Serum creatinine level was lower in negative control and elamipretide groups. It was observed that urine oxalate values ​​on day 5 increased significantly in all groups compared to the negative control group (p = 0.037). Histologically, it was observed that kidney damage was less and mitochondrial damage was reduced in elamipretide groups. When the groups were compared in terms of IL-11, it was found that the gene expression in the placebo group was statistically significantly higher than the other groups and that caspas 1, caspas 9, caspas 11 and NLRP3 gene expression were significantly lower in the negative control group compared to the other groups. There was no significant difference in terms of caspas 1, caspas 9, caspas 11 and NLRP3 gene expression between treatment groups (plasebo vs elamipretid).

Conclusions:

 In this study, it has been shown that elamipretidine reduces mitochondrial damage, and with increased caspas1 and NLRP3 mRNA expressions, the inflammatory pathway is active in oxalate nephropathy, but elamipretide is not effective in suppressing this pathway