Dose-dependent protective effects of theophylline on testicular endocrine function in a rat model of ischemia-reperfusion injury.

INTRODUCTION

Testicular torsion (TT) induces ischemia-reperfusion (I/R) damage, frequently resulting in inflammatory responses, oxidative stress, and compromised spermatogenesis. This study investigated the potential therapeutic role of theophylline-a methylxanthine with established antioxidant and anti-inflammatory properties-on testicular I/R outcomes in a rat model.

METHODS

Thirty-two pubertal Wistar-Albino rats were categorized into four cohorts (n=8 per group): Control, I/R, and I/R treated with either 10 mg/kg or 50 mg/kg theophylline.

RESULTS

While plasma biochemical markers (tumor necrosis factor-alpha (TNF-α), glutathione, myeloperoxidase, ischemia-modified albumin, inhibin B, caspase-3, and testosterone) and histopathological Johnsen tubular biopsy scores remained statistically comparable across groups, significant intergroup variations were observed in testicular tissue TNF-α (p = 0.017), testicular testosterone (p = 0.003), and Cosentino histopathological grades (p < 0.05).Although high-dose theophylline showed a downward trend in tissue TNF-α, this specific pairwise difference did not reach statistical significance.

DISCUSSION: These results indicate that while acute structural protection was limited within a 4-hour reperfusion window, high-dose theophylline demonstrates a promising capacity to preserve testicular testosterone levels and modulate local inflammatory markers. This suggests a dose-dependent supportive effect on Leydig cell function and endocrine recovery following ischemic insult.