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Effect of allopurinol on damage caused by free radicals to cryptorchid testes
Rosa María Vigueras-Villaseñor1, Dora Molina-Ortiz, Gabriela Reyes-Torres
1Subdirección de Medicina Experimental, Instituto Nacional de Pediatría, Mexico; Facultad de Medicina Veterinaria y Zootécnia, UNAM, Mexico. marcoviv@servidor.unam.mx
Abstract:
Cryptorchidism causes apoptosis of germ cells. It has been suggested that the redox regulatory system is involved in this process. The free radicals produced are thought to be generated during the production of uric acid, a reaction catalyzed by xanthine oxidase. This enzyme is inhibited by allopurinol; however, the role of allopurinol in neonate rats with inguinal cryptorchidism has not been assessed yet. Sixty male Wistar rats were used and five groups were formed: a control, a sham, a sham group with allopurinol administration and two groups with surgical unilateral cryptorchidism, which either did not receive, or received, allopurinol. The rats were assessed at 40 days post-partum. Reactive oxygen species concentration and epithelial area were measured and the histopathological, apoptotic and cellular proliferation indexes were determined. We found a decrease in reactive oxygen species, histopathological and apoptotic indexes and an increase in proliferation index and epithelial area in rats with cryptorchidism treated with allopurinol in comparison with rats with untreated cryptorchidism. We suggest that the over-production of reactive oxygen species plays an important role in the damage of the cryptorchid testes. Allopurinol administration decreases reactive oxygen species concentrations as well as the damage to the germ epithelium.
Insights
Allopurinol reduces damage in cryptorchid testes by decreasing reactive oxygen species (ROS). This treatment improved germ cell health and proliferation in neonate rats with undescended testes.
Area of Science:
- Reproductive Biology
- Endocrinology
- Toxicology
Background:
- Cryptorchidism, characterized by undescended testes, leads to germ cell apoptosis.
- The redox regulatory system, involving reactive oxygen species (ROS) and xanthine oxidase, is implicated in this process.
- Allopurinol is a known inhibitor of xanthine oxidase.
Purpose of the Study:
- To evaluate the therapeutic effect of allopurinol on neonatal inguinal cryptorchidism in rats.
- To investigate the role of reactive oxygen species in testicular damage associated with cryptorchidism.
Main Methods:
- Unilateral cryptorchidism was surgically induced in male Wistar rats.
- Five experimental groups were established: control, sham, sham with allopurinol, cryptorchid, and cryptorchid with allopurinol.
- Assessment at 40 days postpartum included ROS concentration, epithelial area, histopathology, apoptosis, and cell proliferation.
Main Results:
- Allopurinol treatment significantly decreased ROS levels and apoptotic/histopathological indexes in cryptorchid testes.
- Conversely, allopurinol increased proliferation index and epithelial area in affected testes.
- Untreated cryptorchid testes showed higher ROS and damage markers compared to controls.
Conclusions:
- Overproduction of reactive oxygen species plays a critical role in the pathogenesis of cryptorchid testicular damage.
- Allopurinol administration mitigates testicular damage by reducing ROS concentrations and protecting germinal epithelium.
