Clozapine-Induced parotid inflammation and the effect of N-Acetyl cysteine on it: An experimental study
European Journal of Pharmacology, cilt.1029, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1029
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.ejphar.2026.179010
- Dergi Adı: European Journal of Pharmacology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: Clozapine, Inflammation, N-acetylcysteine, Oxidative stress, Parotid gland
- Bilecik Şeyh Edebali Üniversitesi Adresli: Evet
Özet
Objective Clozapine is associated with systemic and salivary gland inflammation, but the mechanisms underlying parotid toxicity remain unclear. This study evaluated oxidative stress, inflammatory responses, and histopathological changes in the parotid glands of rats treated with clozapine and investigated the protective effects of N-acetylcysteine (NAC). Methods Thirty-six male Wistar Albino rats were randomly allocated to Control, Clozapine (40 mg/kg/day), or Clozapine + NAC (240 mg/kg/day) groups for 23 days. Serum and parotid tissues were analyzed for total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), TNF alpha, IL-10, and C-reactive protein (CRP). Histopathological assessments included inflammation, nuclear degeneration, ductal dilatation, and mucinous metaplasia. Results Clozapine significantly increased TOS, OSI, TNF alpha, and CRP, while decreasing TAS and IL-10 in both serum and parotid tissue compared to controls (p < 0.05). NAC co-administration reversed these changes, indicating reduced oxidative stress and inflammation. Histologically, clozapine induced periductal, lobular, and periglandular inflammation, nuclear degeneration, and ductal dilatation; these alterations were markedly attenuated by NAC (p < 0.001). Mild mucinous metaplasia was observed in the serous component of the parotid in clozapine-treated rats, independent of NAC treatment. Conclusion Clozapine disrupts antioxidant and inflammatory balance in rat serum and parotid glands, inducing structural and biochemical alterations. NAC co-administration significantly attenuates these effects, suggesting a potential therapeutic role in preventing clozapine-induced parotid toxicity. Further studies are warranted to explore clinical implications for sialorrhea and salivary gland protection.