Bevacizumab and cytostatics induce oxidative changes in the submandibular gland of male rats

Abstract

Objective: To investigate whether the administration of bevacizumab in combinationwith cytostatics could cause an oxidative response in the submandibular gland of ananimal model.Materials and methods: 48 Male Wistar rats (350–400 g) were used. Group 1: Control;Group 2: 5-Flourouracil + Leucovorin calcium (Intraperitoneal injection for fiveconsecutive days with 20 mg/kg+10 mg/kg); Group 3: Bevacizumab, two intraperitonealdoses of 0.2 mg/kg on days 1 and 15; Group 4: Oxaliplatin, one intraperitoneal dose of25 mg/kg on days 1 and 15; Group 5: Bevacizumab+Oxaliplatin+5-Fluorouracil+Leucovorin calcium , single intraperitoneal dose of 20 mg/kg, 10 mg/kg,0.2 mg/kg, and 25 mg/kg on days 1 and 15; Group 6: pair-fed group without drugs. Insubmandibular gland homogenates, Uric Acid, Lipid Peroxides, Aqueous Peroxides, andSuperoxide Dismutase activity were measured. Results: Uric Acid in Groups 1, 3, and 6were higher than in cytostatic groups (p < 0.02, 0.02, and 0.001). Lipid Peroxides andAqueus Peroxides were similar. Superoxide Dismutase Activity was higher in Groups 2,3, 4, 5, and 6 compared to Group 1 (p < 0.0001). In Group 3, Superoxide DismutaseActivity was lower than in cytostatic-treated groups but higher than Group 6 (p < 0.001).Group 2 showed higher activity compared to Groups 3 and 6 (p < 0.0001).Conclusions: Cytostatic treatment exerted a pro-oxidant effect at the acinar level.Conversely, bevacizumab may promote an antioxidant glandular response. Furtherresearch into these treatments´ effects on the stomatognathic system is crucial forimproving quality of life in patients undergoing anti-tumour therapy.