Effect of statins on oxidative DNA damage in diabetic polyneuropathy

Sandra Carrillo-Ibarra; Alejandra Guillermina Miranda-Díaz; Sonia Sifuentes-Franco; Ernesto Germán Cardona-Muñoz; Adolfo Daniel Rodríguez-Carrizalez; Geannyne Villegas-Rivera; Luis Miguel Román-Pintos

doi:10.33393/jcb.2018.2094

Authors

Sandra Carrillo-Ibarra Departament of Physiology, Institute of Clinical and Experimental Therapeutics, University Health Sciences Centre, University of Guadalajara, Guadalajara, Jalisco, México
Alejandra Guillermina Miranda-Díaz Departament of Physiology, Institute of Clinical and Experimental Therapeutics, University Health Sciences Centre, University of Guadalajara, Guadalajara, Jalisco, México
Sonia Sifuentes-Franco Departament of Physiology, Institute of Clinical and Experimental Therapeutics, University Health Sciences Centre, University of Guadalajara, Guadalajara, Jalisco, México
Ernesto Germán Cardona-Muñoz Departament of Physiology, Institute of Clinical and Experimental Therapeutics, University Health Sciences Centre, University of Guadalajara, Guadalajara, Jalisco, México
Adolfo Daniel Rodríguez-Carrizalez Departament of Physiology, Institute of Clinical and Experimental Therapeutics, University Health Sciences Centre, University of Guadalajara, Guadalajara, Jalisco, México
Geannyne Villegas-Rivera Department of Health-Disease Sciences as an Individual Process, Tonala University Centre, University of Guadalajara, Jalisco, México
Luis Miguel Román-Pintos Department of Health-Disease Sciences as an Individual Process, Tonala University Centre, University of Guadalajara, Jalisco, México

DOI:

https://doi.org/10.33393/jcb.2018.2094

Keywords:

Diabetic polyneuropathy, oxidative stress, statins, 8-hydroxy-2′-deoxyguanosine, 8-oxoguanine-DNA-N-glycosylase, superoxide dismutase

Abstract

Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status. Statins have pleiotropic, protective effects on the peripheral nerves of patients with diabetes. The aim of this study was to determine the effects of ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This randomized, double-blind, placebo-controlled, clinical trial comprised outpatients from Guadalajara, Mexico. The inclusion criteria were either gender, age 35–80 years, type 2 diabetes, glycated hemoglobin ≤10%, diabetic polyneuropathy stage 1/2, and signed informed consent. Patients who were taking antioxidant therapy or statins, had hypersensitivity to drugs, experienced organ failure, were pregnant or breastfeeding, or had other types of neuropathy were excluded. We assigned patients to placebo, ezetimibe/simvastatin 10/20 mg, or rosuvastatin 20 mg, and the primary outcomes were 8-hydroxy-2′-deoxyguanosine (8-OHdG) for DNA damage, 8-oxoguanine-DNA-N-glycosilase (hOGG1) for DNA repair, and superoxide dismutase (SOD). Seventy-four patients were recruited. Nine patients were included as negative controls. There were no differences in 8-OHdG between the healthy subjects (4.68 [3.53–6.38] ng/mL) and the DPN patients (4.51 [1.22–9.84] ng/mL), whereas the hOGG1 level was 0.39 (0.37–0.42) ng/mL in the healthy subjects and 0.41 (0.38–0.54) ng/mL in patients with DPN at baseline (p = 0.01). SOD decreased significantly in patients with DPN (5.35 [0.01–17.90] U/mL) compared with the healthy subjects (9.81 [8.66–12.61] U/mL) at baseline (p < 0.001). No significant changes in DNA biomarkers were observed in any group between baseline and final levels. We noted a rise in hOGG1 in patients with DPN, without modifications after treatment. There was a slight, albeit insignificant, increase in SOD in patients who were on statins.