Metformin Mitigates Cisplatin and Paclitaxel Toxicity

After repeat exposure to the test environment and baseline measurements of behavior, C57Bl/6J mice were intraperitoneally (i.p.) treated with cisplatin (Sigma-Aldrich, St. Louis MI) daily at a dosage of 2.3 mg/kg for 5 days, followed by 5 days of rest, for two cycles with a total cumulative dose of 23 mg/kg cisplatin [19] (link). Control mice received an equivalent volume of saline. Metformin hydrochloride (Sigma-Aldrich) was freshly prepared in saline daily. Metformin (200 mg/kg) or saline was given i.p. for seven consecutive days, beginning 24 h prior to the first dose of cisplatin of each cycle or 24 h before the start of the second cisplatin cycle. A separate group of mice was treated with paclitaxel (i.p 10 mg/kg) every other day for two weeks. In this group, metformin (200 mg/kg i.p.) was given daily starting 24 h before the first dose of paclitaxel. On days when both cisplatin or paclitaxel and metformin were administered, metformin was given 30–60 min prior to cisplatin or paclitaxel. Lidocaine hydrochloride (Sigma-Aldrich; 5 µl 4% in saline) or saline was injected into the hind paw of control mice 10 minutes before the adhesive removal test.