Metformin Exerted Neuroprotective Effects on Cognition in Rats with Trastuzumap‐Induced Brain Toxicity

Background Trastuzumap (Trz) is effectively used for breast cancer patients to improve health status and reduce mortality rate. Nevertheless, several studies reported its adverse effect on brain toxicity. To date, the mechanisms of Trz-induced toxicity are not fully understood. Metformin a generic prescribed drug type 2 diabetes mellitus, while in past decade it also attenuating effects chemotherapy. However, metformin mitochondrial function, hippocampal microglial synaptic plasticity, cognitive function have never been investigated. Method Eighteen male Wistar rats were randomly divided into two groups; control group (0.9% NSS, intraperitoneal (i.p.) injection, n = 8) Trz-treated (4 mg/kg 7 days, i.p. 16). Then, subgroups (n 6/ subgroup) receive either vehicle daily via oral gavage) or (250 mg/kg/day gavage). At end experiment protocol, was measured, brains obtained further molecular investigation. Result demonstrated an increase ROS production, increased mean fluorescence intensity ionized calcium binding adaptor molecule 1 (Iba1), decreased dendritic spine density, preferent index novel object location (NOL) recognition (NOR) test (p<0.05, Figure 1A-F). Metformin-treated Trz-rats reversed Trz by attenuated Iba1, as well NOL NOR Conclusion indicated dysfunction, impaired alleviated those deleterious effects. The findings this study emphasize roles against strengthen