Investigation of renal COX-2 distribution of prenatally administered diclofenac sodium in postnatal rats using stereological and immunohistochemical methods

Abstract

While cyclooxygenase-2 (COX-2) plays a critical role in embryonic kidney development. Inhibition of this enzyme by nonsteroidal anti-inflammatory drugs (NSAIDs), commonly used during pregnancy, can adversely affect fetal kidney development. In this study, we examined the postnatal expression and distribution of COX-2 in the kidneys of murine offspring born to mothers administered diclofenac sodium, a COX-2 inhibitor, during gestation, using stereological and immunohistochemical techniques. Twelve female Wistar albino rats were divided into diclofenac sodium (DSG) and control groups (CG). From the 5th day of pregnancy, 1 mg/kg diclofenac sodium was intraperitoneally injected into the DSG, and the CG did not receive any intervention. Twelve kidneys from 4-week-old rats were examined using stereological and immunohistochemical methods. Data were analyzed using the Mann-Whitney U test. COX-2 expression was detected in different regions of postnatal rat kidneys in both groups. COX-2 staining levels were highest in the macula densa and collecting tubules, whereas lower expression was observed in other regions in DSG than in CG. Stereological analyses showed that the total kidney volume increased significantly in the DSG, and the differences in COX-2 staining intensity were statistically significant (p < 0.05). Our findings suggest that COX-2 inhibitor use during pregnancy may adversely affect kidney development. Given the critical role of COX-2 in renal function, the use of NSAIDs during pregnancy should be carefully evaluated. Our study highlights the need for further experimental studies to understand the effects of prenatal exposure to diclofenac sodium on renal morphology and COX-2 expression.