Pharmaceutical and Biomedical Research

en Combined Exposure to Chlorpyrifos and Chronic Heat Stress Induces Endpoint-Specific Toxicity in the Male Rat Reproductive System سم شناسی Toxicology پژوهشي Original Research Background: Concurrent occupational exposure to organophosphate pesticides like chlorpyrifos (CPF) and rising environmental heat stress (HS) represents an underexplored male reproductive hazard. Objectives: This study aimed to characterize the combined subchronic effects of CPF and chronic HS on the male rat reproductive system and to evaluate whether these physical and chemical stressors interact additively, synergistically, or antagonistically.  Methods: Twenty male Wistar rats were randomized into four groups (n = 5/group) for 30 days: Control, CPF (8 mg/kg/day via gavage), HS (38°C, 2 h/day), and CPF+HS. Serum reproductive hormones, epididymal sperm parameters, and testicular oxidative biomarkers (ROS, MDA, GSH, SOD) were evaluated using two-way ANOVA. Results: Individual exposures significantly increased oxidative stress and impaired sperm quality and hormone levels (p < 0.05). In the co-exposure (CPF+HS) group, testicular oxidative biomarkers and sperm parameters exhibited a non-additive, near-ceiling response dominated by CPF toxicity (p > 0.05 versus CPF alone). Conversely, a significant CPF × HS interaction was observed for serum testosterone (1.05 ± 0.04 ng/mL) and LH (3.12 ± 0.04 mIU/mL) (p < 0.001), indicating an enhanced suppressive response following combined exposure. In contrast, FSH showed an additive decline without a significant interaction (p = 0.148). Conclusion: Combined chemical-thermal exposure induces endpoint-specific toxicity. Testicular oxidative damage and sperm quality are restricted by a CPF-driven metabolic ceiling effect, whereas the HPT axis exhibits enhanced vulnerability via synergistic hormone suppression, highlighting the limitations of simple additive risk models.   Chlorpyrifos, Heat Stress Disorders, Oxidative Stress, Spermatozoa 0 0 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-1502-1&slc_lang=en&sid=1 solale ramzani solale.ramezani@modares.ac.ir 100319475328460012394 100319475328460012394 No Department of Occupational Health and Safety Engineering, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Seyyed Bagher Mortazavi mortazav@modares.ac.ir 100319475328460012395 100319475328460012395 Yes Department of Occupational Health and Safety Engineering, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Mohammad Shokrzadeh mshokrzadeh@mazums.ac.ir 100319475328460012396 100319475328460012396 No Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran Ali Khavanin khavanin@modares.ac.ir 100319475328460012397 100319475328460012397 No Department of Occupational Health and Safety Engineering, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran