Ellagic acid attenuates testicular disruption in rheumatoid arthritis via targeting inflammatory signals, oxidative perturbations and apoptosis.

BACKGROUND AND PURPOSE: Reduced male fertility has been regarded as a serious complication of rheumatoid arthritis. Phytochemicals have been described as protective agents against rheumatoid arthritis-linked testicular impairment. The current study aimed to investigate the potential protective effects of ellagic acid on rheumatoid arthritis-evoked testicular dysfunction vis-à-vis the reference anti-inflammatory celecoxib.

EXPERIMENTAL APPROACH: Ellagic acid (50 mg/kg/day) and celecoxib (5 mg/kg/day) were administered orally for 20 days in adjuvant-induced arthritic rats.

KEY FINDINGS: Current data revealed that ellagic acid counteracted rheumatoid arthritis-evoked testicular histopathologic changes, disrupted sperm characteristics and low gonadosomatic index with comparable efficacy to celecoxib. Ellagic acid also enhanced the testicular steroidogenesis via upregulating the gene expression of 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein with consequent boosting of serum testosterone. Notably, ellagic acid attenuated the testicular inflammatory responses through suppression of myeloperoxidase, tumor necrosis factor-α and cyclo-oxygenase-2 protein expression together with enhancing the anti-inflammatory signal interleukin 10. Ellagic acid also curbed the redox alterations via lowering the production of lipid peroxides and nitric oxide and elevation of the anti-oxidant reduced glutathione. In support of cell survival, ellagic acid combated testicular apoptosis through downregulating caspase-3 protein expression.

SIGNIFICANCE: The present work accentuates the beneficial actions of ellagic acid in rheumatoid arthritis-incurred testicular impairment and disrupted spermatogenesis via combating the inflammatory, oxidative and apoptotic aberrations.