Lightning Talk + Poster ESA-SRB-ANZOS 2025 in conjunction with ENSA

Understanding diabetic kidney disease (DKD), COVID-19 infection, and mitochondrial dysfunction (129108)

Ellen N Tejo 1 , Rani Whiddett 1 , Chengxiang Foo 1 , Katharina Ronacher 1 , Chenping Du 1 , Amelia Fortheringham 1 , Domenia McCarthy 1 , Saee Zambre 1 , Josephine Forbes 1 2 3 4 , Mitchell Sullivan 1 5 6
  1. Glycation and Diabetes Complication, Mater Research Institute - The University of Queensland, the Translational Research Institute (MRI-UQ, TRI), Brisbane, QUEENSLAND, Australia
  2. Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  3. Mater Hospital, Mater Misericordiae Ltd, Brisbane, Queensland, Australia
  4. Department of Medicine, University of Melbourne, Brisbane, Queensland, Australia
  5. Centre for Bioinnovation and School of Health, University of Sunshine Coast, Sippy Downs, Queensland, Australia
  6. Sunshine Coast Health Institute, Birtinya, Queensland, Australia

The comorbidities of diabetes and COVID-19 have been strongly associated with increased morbidity and mortality. Previous studies have linked both diseases with kidney damage and mitochondrial dysfunction. Considering the importance of mitochondrial dysfunction in both diabetes and COVID-19, we hypothesized that improving mitochondrial function would be an effective treatment strategy for preventing kidney damage when these diseases are present.

To investigate this, male C57Bl6/J mice (n=12-16/group) were assigned to 5 groups: 1) non-diabetic,non-treated,and non-infected; 2) non-diabetic,non-treated,and infected; 3) non-diabetic,treated,and infected; 4) diabetic,non-treated,and infected; and 5) diabetic,treated,and infected. MitoA is an antioxidant compound that has demonstrated potency and efficacy in ameliorating mitochondrial dysfunction in other mitochondrial diseases. Type1 Diabetes was induced in the diabetic groups by 5 daily intraperitoneal injections of low-dose streptozotocin (STZ, 55 mg/kg/day) at 5 weeks of age. Groups that received MitoA treatment were given a daily dose via oral gavage, with control groups receiving saline. At 18 weeks of age, the COVID-infected groups were infected with mouse-adapted strains of the SARS-CoV-2 virus via respiratory injection and monitored daily. When the average body weight of one group decreased by over 20% of the pre-infection body weight, mice from all groups were euthanised.

Post-infection body weight measurements showed that COVID-19 infection significantly decreased body weight, with the group that was diabetic, untreated, and infected being affected most severely. The body weight decrease was significantly reduced in groups receiving MitoA treatment, with or without diabetes.

The infected diabetic group that received daily MitoA treatment showed significantly less overall kidney damage (measured by Glomerular Sclerosis Index) and qualitatively less fibrosis (measured by Sirius Red staining) when compared to the untreated group. MitoA treatment had no noticeable effect on blood glucose control. These results suggest that MitoA may ameliorate some of the effects of diabetes and COVID-19 infection on kidney health.