Chrysin as a multi-target regulator of tramadol-induced testicular damage: Integration of inflammation, mitochondrial dynamics, and germ cell survival pathways.

Authors

İbrahim Erol, Selçuk Özdemir, Sefa Küçükler, Mustafa Özkaraca, Serkan Ali Akarsu, Hasan Şimşek, Hamit Emre Kızıl, Hüseyin Mutlu, Fatih Mehmet Kandemir

Published in

Toxicology and applied pharmacology. Pages 118081. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

Tramadol, although commonly utilized as an analgesic, is an opioid derivative that may induce significant adverse consequences on the reproductive system. This study experimentally assessed the toxic effects of tramadol on testicular tissue and reproductive capabilities, as well as the protective capability of chrysin (CHR) against these effects. The results indicated that tramadol treatment caused considerable functional impairment in testicular tissue, as reflected by a notable reduction in sperm count, motility, and morphology, an elevation in the Cosentino score, and a decline in the Johnsen score and germinal epithelial thickness. Moreover, tramadol inhibited the hypothalamo-pituitary-gonadal axis by reducing testosterone, FSH, and LH levels. At the molecular level, tramadol induced heightened oxidative stress, inhibited antioxidant defense mechanisms, intensified the inflammatory response, and compromised mitochondrial function. Furthermore, an elevation in DNA damage indicators and a notable activation of the cellular stress response were observed. Substantial disturbances were also noted in miRNA expression patterns and the control of target genes. Nonetheless, CHR therapy predominantly ameliorated all functional, hormonal, and molecular alterations induced by tramadol. Spermatogenesis was partially reinstated, and sperm parameters together with hormone levels approached values comparable to those of the control groups. Moreover, substantial advancements were attained in oxidative stress, inflammation, mitochondrial dysfunction, and DNA damage indicators. In conclusion, CHR has significant protective and regulatory actions against tramadol-induced testicular damage.

PMID:
42874878
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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