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

Vida  Motamed Nia; Nastaran  Rezaei; Mohammad  Shokati Sayyad; Mohammad  Seyedabadi; Fereshteh Talebpour  Amiri; Fatemeh  Shaki

doi:10.18502/jri.v25i3.17014

Vida Motamed Nia Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Nastaran Rezaei Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Mohammad Shokati Sayyad Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Mohammad Seyedabadi Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
Fereshteh Talebpour Amiri Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Scienc-es, Sari, Iran
Fatemeh Shaki Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

DOI: https://doi.org/10.18502/jri.v25i3.17014

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

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.