The Protective Effects of Citrulline on Testicular Injury Induced by Torsion and Detorsion in Adult Male Rats: An Experimental Study

Abstract

Background: Testicular torsion is a critical urological emergency that can lead to testicular ischemia and significant tissue damage. Citrulline, a supplement known for enhancing cellular metabolism and mitigating oxidative stress and inflammation, has been explored for its protective effects against testicular injury resulting from torsion and detorsion in rat models.

Methods: This study involved 42 Wistar rats, divided into six groups: Sham, torsion/detorsion (T/D), and four groups receiving varying doses of Citrulline (300, 600, 900 mg/kg) and vitamin E (20 mg/kg). A surgical procedure was performed to induce torsion by rotating the left testicle for 4 hr, followed by reperfusion. Daily oral administration of the supplements continued for one week post-surgery. Assessments included oxidative stress markers, apoptosis, inflammation, pathology, and sperm parameters. Statistical analysis was conducted using GraphPad Prism.

Results: Citrulline administration at doses of 600 and 900 mg/kg significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Additionally, it increased glutathione (GSH) levels and decreased protein carbonyl levels at the 900 mg/kg dose. The expression of interleukin-6 (IL-6) decreased at 900 mg/kg, tumor necrosis factor-alpha (TNF-α) levels dropped at 600 and 900 mg/kg, and the pro-apoptotic factor Bax was reduced at all doses. Sperm analysis showed improved sperm count and motility at the 900 mg/kg dose. Histological examination revealed significant positive effects of Citrulline on testicular tissue.

Conclusion: Citrulline effectively lowers oxidative stress, inflammation, while enhancing sperm quality and pathological outcomes. These results indicate that Citrulline has potential as a therapeutic agent for testicular torsion.

Keywords: Citrulline; Inflammation; Oxidative stress; Testis; Torsion.

Figure 1.

H&E-stained histology of testis showing (A) Sham group, (B) torsion/detorsion (T/D) group, (C) vitamin E group (20 mg/kg), (D) torsion/detorsion (T/D) group with a therapeutic dose of 300 mg/kg (T/D+Cit300), (E) torsion/detorsion (T/D) group with a therapeutic dose of 600 mg/kg (T/D+Cit600), and (F) torsion/detorsion (T/D) group with a therapeutic dose of 900 mg/kg (T/D+Cit900). Thick black arrow: loss of integrity; Thin black arrow: edema - increased distance between seminiferous tubules; Black double-headed arrow: diameter of seminiferous tubule. Magnification: 20× and scale bar:100 μm