Protective effects of diallyl trisulfide (DATS) against doxorubicin-induced inflammation and oxidative stress in the brain of rats

• Published in: Free radical biology & medicine 2020-11, Vol.160, p.141-148
• Main Authors: Leung, Wai-Shing, Kuo, Wei-Wen, Ju, Da-Tong, Wang, Tian-De, Shao-Tsu Chen, William, Ho, Tsung-Jung, Lin, Yu Min, Mahalakshmi, B., Lin, Jing-Ying, Huang, Chih-Yang
• Format: Article
• Language: English
• Subjects: Diallyl trisulfide (DATS); Doxorubicin (DOX); Inflammation; Oxidative stress; Tumor necrosis factor-alpha (TNF-α)
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.07.018

Doxorubicin (DOX) is a widely used antitumor drug that causes severe neurotoxicity in patients. Diallyl trisulfide (DATS) is an organosulfur compound with established potent antioxidant and anti-inflammatory properties. Herein, we investigated the neuroprotective efficacy of DATS in preventing DOX-induced neurotoxicity in a rat model. Specifically, DATS (40 mg/kg) was administered to rats 24 h after DOX treatment, once a week for 8 weeks. Our results showed that DATS treatment led to a decrease in plasma levels of tumor necrosis factor-alpha (TNF-α) induced by DOX. DATS restored cerebral cortex and hippocampus histopathological architecture and neuronal loss. Immunohistochemical staining indicated that DATS decreased the expression of glial fibrillar acidic protein (GFAP) in DOX treated rats. Components of stress-related inflammatory proteins (TNF-α, phospho nuclear factor kappa B (NF-κB), inducible nitricoxide synthase (iNOS) and cyclooxygenase-2 (COX-2)) were all significantly increased in the DOX group, in comparison with the control group, whereas they were decreased after DATS treatment. In addition, the mRNA of antioxidant enzymes (superoxide dismutase 2 (SOD2), catalase, glutathione peroxidase 1, 4 (GPx1 and GPx4)) and antioxidant proteins (heme oxygenase-1 (HO-1), superoxide dismutase 1, 2 (SOD1 and SOD2), Γ-glutamylcysteine synthase (Γ-GCSc)) were markedly increased in DOX group compared with the control group, which were significantly attenuated by DATS treatment. The upregulation of antioxidants enzymes in DOX group was probably a compensatory effect against elevated oxidative stress induced by DOX. DATS treatment could ameliorate this oxidative stress in brain. Our results suggested that DATS has potential clinical applications in the prevention of DOX-induced neurotoxicity by ameliorating inflammatory insults and oxidative stress. [Display omitted] •DATS inhibit DOX-induced TNF-α release in peripheral plasma and brain.•DATS decreased DOX-induced the GFAP expression level in cerebral cortex.•DATS has strong anti-inflammatory effects in the brain by inhibiting TNF-α/NFκB/iNOS/COX2 signaling pathway.•DATS ameliorated DOX-induced oxidative stress in brain and achieved brain tissue protection.