Effects of Hydroxychloroquine Used in Fracture Healing on Oxidative Stress and DNA Damage in Rat Tissues

Hydroxychloroquine is an aminoquinoline derivative drug widely used in the treatment of autoimmune diseases, rheumatoid arthritis, and malaria. In 2020, it was approved by the FDA for the treatment of COVID-19, despite a lack of clear evidence of efficacy/safety based solely on in vitro data. In our previous study, we demonstrated that orally administered hydroxychloroquine in rats impaired bone fracture healing, attributing this to increased oxidative stress in the blood. In this study, based on our previous results, we aimed to investigate the effects of the drug on oxidative stress and DNA damage that may develop over time in liver, kidney, and brain tissues in the same model. In the study, antioxidant enzyme activities and lipid peroxidation were measured as parameters of oxidative stress, and the Comet assay was used to determine potential DNA damage in rat tissues. While a dose-independent increase was observed in MDA levels in the liver and brain, the level of MDA in the kidney increased dose-dependently. DNA damage results were also consistent with MDA levels. Although oxidative damage due to bone fracture formation in the control groups showed a time-dependent change, it was not statistically significant. Our findings clearly demonstrate that hydroxychloroquine causes oxidative stress and DNA damage in the liver, kidney, and brain tissues of rats with bone fracture.