Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Abstract

Objective: The present study aimed to investigate the possible postnatal effects on the liver, kidney and testicular tissues of the offspring of rats given diclofenac sodium (DS) during pregnancy. Methods: At the beginning of the experiment, 80 rats (20 males and 60 females) were raised together for mating purposes. At the end, 50 pregnant rats were obtained and used as the experimental subjects. All pregnant rats were divided into 2 groups, each with 25 rats. The rats of the control group received physiological serum, 1 cm³/kg live weight per day, and the rats of the treatment group were injected with DS, 1 mg/kg live weight per day from the 5th to the 20th day of pregnancy. Four weeks after birth, tissue samples were obtained under anesthesia by perfusion fixation from a total of 40 offspring, 20 (10 males, 10 females) from the control group and 20 (10 males 10 females) from the DS group. Paraffin sections were dyed with hematoxylin eosin and examined under light microscopy. Results: The gestation period was significantly prolonged with DS-treated rats (p < 0.001). A moderate significant enlargement in the periportal area (p < 0.05), sinusoidal dilatation (p < 0.001), bile duct proliferation (p < 0.001), pyknosis in the nucleus of hepatocytes, and vacuolar degeneration in parenchymal cells (p < 0.001) were observed in DS-treated rats. Morphological changes in the liver were found to be similar both in female and male rats. Under light microscopy a similar morphological structure was observed in the kidney and testicular tissues of both the DS-treated and control rats. Conclusion: Significant morphological changes were observed in the livers of the offspring whose parents had been treated with DS. No significant differences were observed in liver morphology between the female and male offspring. There were no significant effects of DS on the morphology of the kidney and testis in all offspring.

Natural remedies for non‐steroidal anti‐inflammatory drug‐induced toxicity

“…It will affect the mechanism of oxidative stress and causes damage to cells and cellular compounds (Khan & Ahmed, 2009). The activity of diclofenac results in the elevation of ROS, which ultimately results in peroxidative damage in the kidney (Della Torre et al, 2016;Gökçimen et al, 2001). Studies on diclofenac-induced rats have been observed to exhibit anemia.…”

Maternal diclofenac sodium ingestion and severe neonatal pulmonary hypertension

“…Recently, there is evidence of good placental transfer of DS in human; the concentration of DS in fetal tissue was high and similar to that of maternal serum 5 . DS has also been shown to have teratogenic and postnatal effects in rat models 6,7 . Animal studies had proven the development of tricuspid regurgitation, atrial right to left shunting, and right ventricular hypertrophy as the result of sustained right ventricular overload after fetal ductus ligation 8−10 .…”

“…5 DS has also been shown to have teratogenic and postnatal effects in rat models. 6,7 Animal studies had proven the development of tricuspid regurgitation, atrial right to left shunting, and right ventricular hypertrophy as the result of sustained right ventricular overload after fetal ductus ligation. [8][9][10] In addition, fetal pulmonary hypertension due to intrauterine closure of the ductus also gives rise to media thickening of pulmonary arterioles, which impede the postnatal fall in pulmonary vascular resistance.…”

Effects of prenatally exposed diclofenac sodium on rat heart tissue:a stereological and histological study

“…Our study indicates that a reduction in cardiac ventricular wall volume and the histological changes observed in the cardiac ventricular muscle are not directly due to the contraction of DA. They may be the combined effects of DS and its metabolites and the side effects of DS-deregulated umbilical cord blood circulation (36). Two different examinations were made of the 20-weekold rats, which were exposed to the same DS doses during the same period and days of uterine life.…”