Investigation of endoplasmic reticulum stress in ipsilateral and contralateral kidneys after unilateral partial and complete ureteral obstruction in rats

Aim: Although many studies have been conducted on ureteral obstruction, the effect of PUO, which is more common in clinical practice, on ERS is unknown. In addition, there is no study comparing the effects of complete and partial ureteral obstruction on ERS in the same experimental model. In order to investigate these effects, it was aimed to determine the presence of ERS in the ipsilateral and contralateral kidneys of rats with unilateral PUO and CUO and its relationship with renal parenchymal apoptosis using immunohistochemical and molecular biological methods. Material and method: In this study, a total of 24 Wistar rats, 21 days old, were divided into 4 groups, each containing 6 rats: Control (C) group, sham (S) group, partial ureteral obstruction (PUO) group, and complete ureteral obstruction (CUO) group. Group K: No surgical procedure was performed. S group: After laparotomy, the proximal ureter was only dissected from the psoas muscle and no obstruction was performed. PUO group: The proximal ureter was dissected and released by laparotomy and embedded in the psoas muscle at two points. CUO group: The proximal ureter was dissected and released by laparotomy and ligated at two points to create complete obstruction. At the end of the two-week experiment period, the subjects belonging to all groups were sacrificed and the ipsilateral and contralateral kidneys were removed. After macroscopic/morphological measurements of the kidneys, each kidney tissue was divided into two parts and sent to the laboratory under suitable conditions for histopathological and molecular biological examinations. Expression levels of GRP78 and CHOP as ERS markers and cleaved caspase-3 proteins as apoptotic markers in sections obtained from kidney tissues were evaluated by immunohistochemical method, and also GRP78 and CHOP mRNA expression levels were evaluated by RT-PCR. Results: According to the H&E staining findings of our study, atrophy in the kidneys, shrinkage of the glomeruli, enlargement of the Bowman's space and degeneration of the tubules occurred as a result of unilateral partial and complete ureteral obstruction. Significantly increased expression of GRP78 was observed in both the medulla and cortex in the ipsilateral kidneys of the CUO and PUO rat groups, compared to the other kidneys. There was a significant increase in the expression of CHOP in the ipsilateral kidney cortices of rats in the CUO and PUO groups, compared to the contralateral kidneys, while no difference was detected in the medulla between all groups. When the expression level of cleaved caspas-3 was evaluated to determine the level of apoptosis mediated by ERS, no significant change was observed in the kidneys of the PUO group, while an increase expression was observed in both the ipsilateral and contralateral kidneys of the rats in the CUO group. When the mRNA expressions of GRP78 and CHOP proteins were evaluated, it was observed that there was a significant increase of GRP78 mRNA level in the ipsilateral kidneys of the PUO group, but no such increase in the CUO group. When CHOP mRNA expression was examined, no increase was observed in the ipsilateral kidneys in the PÜO and CUO groups, while an increase was observed in the contralateral kidneys, although not statistically significant. Conclusion: ERS in unilateral PUO and CUO experimental models plays an important role in renal parenchymal damage. The findings seen in the CUO group are much more severe and destructive. Cell damage is prevented by suppressing the ERS that occurs in PUO by protective mechanisms. In terms of correlation with clinical practice, there is a need to investigate which molecules can suppress ERS with partial obstruction experimental models and molecules that can be brought into clinical practice as a result of these studies. Keywords: Kidney, ureteral obstruction, endoplasmic reticulum stress