The effects of different inhibitory pathways of prostaglandine 2 biosynthesis on renomedullary in terstitial cells in rats

Abstract

Introduction: Renomedullar interstisial cells (RMiCs) are the prevalent cells in inner medulla. The multiple lipid granules found in their cytoplasm are believed to be storage units for precursors of prostaglandins (PGs), prostacyclins and medullipin, particulary PGE2. The aim of the study was to examine the effects due to the inhibition of PGE2 synthesis via different pathways on the RMIC function, the number of lipid granules, medullary hyaluronan (HA) content and cell viability. Materials and Methods: Thirty-two adult male Wistar albino rats, 180-200g, were randomly divided into four groups (n=8): The control group was treated with intraperitonal (ip) 0.9% isotonic salt water; the second group was injected with dexamethasone (DEX) (3 mg/kg, 10 days), inhibiting AA release and PG synthesis by PLA2; the third group was treated with ip indomethasine (IND) (1 mg/kg, 10 days) to inhibit non-specific COX; the fourth group was injected with ip celecoxib (CXB) (1 mg/kg, 10 days) to examine selective COX-2 inhibition. Ten days later, the dissected renal medullas of sacrificed animals were analyzed with light and electron microscopy. The lipid granules were counted in 50 random RIMCs for each animal (x 6.000 magnification). Results: The morphometric analysis showed that the number of lipid granules is significantly decreased in DEX group, and it is significantly increased in IND and CXB groups when compared to the control group. Moreover, medullary HA content and CD44 immunoreactivity were significantly increased in DEX, IND and CXB groups compared to control group. Regarding cell viability, we found that RMIC apoptosis was significantly higher in PGE2 inhibited groups when compared to control group. Coclusions: These results suggest that lipid granules may be numerical and functionally influenced by PGE2 changes. The functional changes in RMICs through PGE2 may influence HA amount of medulla interstitium, the granules might be storage units of AA and finally, PGE2 inhibition may lead to RMIC apoptosis. Besides, 24 hours urine values collected on the 10th day were significantly increased in DEX and IND groups, but similar to the values of control group in CXB group.