ArticleJournal of applied biomedicine2026
Oxaliplatin-induced testicular toxicity is associated with transglutaminase-4 upregulation, hormonal dysregulation, and inflammatory responses.
Article in Journal of applied biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Oxaliplatin-induced toxicity presents a major challenge in cancer management because of its damaging effects on normal tissues, including the reproductive system. Transglutaminase 4 (TG4), a member of the transglutaminase enzyme family, is known for its role in protein cross-linking and cellular stress responses, but its role in chemotherapy-induced reproductive toxicity remains poorly understood. This study examines the impact of oxaliplatin, a platinum-based chemotherapeutic drug, on TG4 expression, enzymatic activity, and testicular toxicity in a rat model following intraperitoneal administration of oxaliplatin (10 mg/kg body weight weekly for six weeks). Biochemical analysis revealed significant hormonal and inflammatory alterations, including elevated serum interleukin-1β (IL-1β) levels, decreased testosterone concentrations, and increased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. These endocrine disturbances were accompanied by significant upregulation of TG4 expression in oxaliplatin-treated testicular tissue (OXP-TT), as demonstrated by quantitative real-time reverse transcription PCR (qRT-PCR) and immunohistochemical (IHC) analyses. Immunofluorescence (IF) further confirmed enhanced TG4 localization within both interstitial and seminiferous tubular regions. In addition, expression of the pro-inflammatory cytokines IL-6 and TNF was significantly increased. A marked elevation in total transglutaminase enzymatic activity was also detected in oxaliplatin-treated tissues. Collectively, these hormonal, inflammatory, and structural alterations occurred concurrently with increased TG4 expression and transglutaminase activity, suggesting that TG4 participates in the testicular response to oxaliplatin-induced stress. These findings indicate that TG4 is associated with chemotherapy-related reproductive toxicity and may represent a stress-responsive indicator of testicular injury. Further studies are required to determine whether TG4 plays a protective or pathogenic role in oxaliplatin-induced testicular damage and to evaluate its potential relevance in preserving fertility during platinum-based chemotherapy.
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