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

Objective

To investigate whether the administration of bevacizumab in combination with cytostatics could cause an oxidative response in the submandibular gland of an animal 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 five consecutive days with 20 mg/kg+10 mg/kg); Group 3: Bevacizumab, two intraperitoneal doses of 0.2 mg/kg on days 1 and 15; Group 4: Oxaliplatin, one intraperitoneal dose of 25 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. In submandibular gland homogenates, Uric Acid, Lipid Peroxides, Aqueous Peroxides, and Superoxide Dismutase activity were measured. Results: Uric Acid in Groups 1, 3, and 6 were higher than in cytostatic groups (p < 0.02, 0.02, and 0.001). Lipid Peroxides and Aqueus 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 Dismutase Activity 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. Further research into these treatments' effects on the stomatognathic system is crucial for improving quality of life in patients undergoing anti-tumour therapy.