Metformin Alleviates Renal Fibrosis

All experiments received prior approval from the Austin Health Animal Ethics Committee which operates under guidelines prepared by the National Health and Medical Research Council (NHMRC), the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and Animal Welfare Victoria. Since this was an entirely animal study, the requirement for consent was waived. The unilateral ureteric obstruction (UUO) model was used to create renal fibrosis as previously described [10 (link)]. In brief, this involved taking male C57Bl/6 mice who were 8–10 weeks old and tying off one of their ureters via a standard surgical technique under isofluorane anaesthesia. Mice were monitored twice daily for weight loss, other signs of distress or evidence of poor health. They received buprenorphine subcutaneous injections for pain in the first three days post-operatively. Seven days later, the mice were sacrificed and a nephrectomy performed. This was done under ketamine anaesthesia with a sufficient dose to provide euthanasia. The obstructed kidney was then used for analysis. In one arm of the study metformin was also added to the mice’s drinking water for three days prior to and during the experiment. Liquid metformin hydrochloride (Focus Pharmaceuticals, London, UK) 0.08mg/mL was added into the drinking water and changed every 48 hours.