title: Ubiquinone (coenzyme Q10) prevents renal mitochondrial dysfunction in an experimental model of type 2 diabetes.
abstract: Cardiovascular benefits of ubiquinone have been previously demonstrated, and we administered it as a novel therapy in an experimental model of type 2 diabetic nephropathy. db/db and dbH mice were followed for 10 weeks, after randomization to receive either vehicle or ubiquinone (CoQ10; 10mg/kg/day) orally. db/db mice had elevated urinary albumin excretion rates and albumin:creatinine ratio, not seen in db/db CoQ10-treated mice. Renal cortices from db/db mice had lower total and oxidized CoQ10 content, compared with dbH mice. Mitochondria from db/db mice also contained less oxidized CoQ10(ubiquinone) compared with dbH mice. Diabetes-induced increases in total renal collagen but not glomerulosclerosis were significantly decreased with CoQ10 therapy. Mitochondrial superoxide and ATP production via complex II in the renal cortex were increased in db/db mice, with ATP normalized by CoQ10. However, excess renal mitochondrial hydrogen peroxide production and increased mitochondrial membrane potential seen in db/db mice were attenuated with CoQ10. Renal superoxide dismutase activity was also lower in db/db mice compared with dbH mice. Our results suggest that a deficiency in mitochondrial oxidized CoQ10 (ubiquinone) may be a likely precipitating factor for diabetic nephropathy. Therefore CoQ10 supplementation may be renoprotective in type 2 diabetes, via preservation of mitochondrial function.
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia. Electronic address: Karly.Sourris@bakeridi.edu.au.
authors.forename: Karly C
authors.initials: KC
authors.lastname: Sourris
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia.
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Harcourt
authors.affiliation: Department of Pediatrics, Department of Pathology, and Department of Laboratory Medicine, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Tang
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Morley
authors.affiliation: Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia; Heart Failure Pharmacology, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia.
authors.forename: Karina
authors.initials: K
authors.lastname: Huynh
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Penfold
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia.
authors.forename: Melinda T
authors.initials: MT
authors.lastname: Coughlan
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia.
authors.forename: Tuong-Vi
authors.initials: TV
authors.lastname: Nguyen
authors.affiliation: Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia; Heart Failure Pharmacology, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Ritchie
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart Research Institute, Melbourne, VIC 3004, Australia; Department of Immunology and Department of Medicine, Monash University, Alfred Medical Research Education Precinct, Melbourne, Australia; Mater Medical Research Institute, South Brisbane, QLD, Australia.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000419:Albuminuria / Q000188:drug therapy; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D005260:Female; D000072596:Hepatitis A Virus Cellular Receptor 1; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000652:urine; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D055316:Cystatin C; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D000255:Adenosine Triphosphate; D003404:Creatinine; D002950:Citrate (si)-Synthase; C024989:coenzyme Q10