High-Dose Oral Ibuprofen in Treatment of Patent Ductus Arteriosus in Full-Term Neonates

Background: Patent ductus arteriosus (PDA) is an important risk for heart failure due to left to right shunt in term neonates. Objectives: In this study, we evaluated the effect of high dose ibuprofen in closure of PDA in term neonates. Patients and Methods: We used double dose ibuprofen (20 mg/kg, 10 mg/kg, and 10 mg/kg) for 3 - 30 day old term neonates with PDA who were admitted in the neonatal wards of Shiraz University of Medical Sciences. The results of this study were compared to the data of the previous study in our center which used the low dose of ibuprofen (10 mg/kg, 5 mg/kg, and 5 mg/kg). Results: 29 full term neonates received high-dose ibuprofen, in 18 neonates, PDA was closed after 4 days (62.1% versus 43.3% for the standard dose and 4.7% for the control group in the previous study) (P = 0.001). The results showed no significant correlation between the closure rate and gestational age, postnatal age, sex, and weight. In the 4th day of treatment, size of the pulmonic end of ductus arteriosus decreased from 2.09 mm to 0.77 mm compared to 1.68 mm to 0.81 mm in the standard dose of oral ibuprofen and 2.1 mm to 1.4 mm in the control group (P = 0.046). Conclusions: This study indicated that high-dose oral ibuprofen was more effective in closing or decreasing the size of PDA.

Early and late effects of Ibuprofen on mouse sperm parameters, chromatin condensation, and DNA integrity in mice

Background: There are few studies indicating the detrimental effects of ibuprofen on sperm fertility potential and DNA integrity. Objective: To determine the effects of Ibuprofen on sperm parameters, chromatin condensation and DNA integrity of mice. Materials and Methods: In this experimental study, 36 adult male mice with average weight 37 gr were divided into three groups, including control (group I, n=12), normal dosage of ibuprofen (group II, n=12) and high dosage (group III, n=12). Ibuprofen with different doses was dissolved in daily water of animals. After 35, 70 and 105 days, the cauda epididymis of mice were cut and incubated in Ham’s F10 media. Sperm samples were analyzed for parameters (motility, morphology and count), DNA integrity (SCD test) and chromatin condensation (chromomycin A3 and Aniline blue staining). Results: After 35 days, in addition to above mentioned sperm parameters, all of the treated mice showed statistically significant increase in spermatozoa with immature chromatin (P<0.05). However, after 70 days, the rate of sperm DNA fragmentation assessed by SCD was increased in group II (66.5±0.7) and the percentage of immature spermatozoa (AB+ and CMA3+) was higher in group III (77.5±0.7 and 49.5±6.3 respectively) than other groups. After 105 days, the AB+ spermatozoa were increased in both normal dose and high dose groups. Conclusion: Ibuprofen may cause a significant reduction in sperm parameters and sperm chromatin/DNA integrity in mice. It should be noted that these deleterious effects are dose-dependent and can be seen in early and late stage of drug treatments.