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Joint Diseases and
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Original Article · Open access

Hydroxychloroquine induces oxidative stress and impairs fracture healing in rats

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Duran Topak

Department of Orthopedics and Traumatology, Kahramanmaraş Sütçü Imam University Faculty of Medicine, Kahramanmaraş, Türkiye

ORCID: 0000-0002-1442-3392

Kaan Gürbüz

Department of Orthopedics and Traumatology, Kayseri City Education and Research Hospital, Kayseri, Türkiye

ORCID: 0000-0002-0144-5517

Fatih Doğar

Department of Orthopedics and Traumatology, Kahramanmaraş Sütçü Imam University Faculty of Medicine, Kahramanmaraş, Türkiye

ORCID: 0000-0003-3848-1017

Elçin Bakır

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Türkiye

ORCID: 0000-0001-5333-8273

Perihan Gürbüz

Department of Pharmacognosy, Faculty of Pharmacy, Erciyes University, Kayseri, Türkiye

ORCID: 0000-0002-3056-411X

Emine Kılınç

Department of Pathology, Kahramanmaraş Sütçü Imam University Faculty of Medicine, Kahramanmaraş, Türkiye

ORCID: 0000-0002-1032-651X

Ökkeş Bilal

Department of Orthopedics and Traumatology, Kahramanmaraş Sütçü Imam University Faculty of Medicine, Kahramanmaraş, Türkiye

ORCID: 0000-0002-7949-5434

Ayşe Eken

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Türkiye

ORCID: 0000-0003-4830-5770

Abstract

Objectives: The aim of this study was to investigate whether hydroxychloroquine sulfate (HCQS) induced oxidative stress and how it affected the union of bone fractures in an experimental rat model.

Materials and methods: A total of 48 Wistar albino male rats were used. The rats were divided into six groups. To investigate the effects of oral administration of HCQS at varying doses between the third and sixth weeks, fracture healing processes were evaluated using radiography, histopathology, biochemistry, and dual-energy X-ray absorptiometry. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured to analyze the relationship between HCQS and oxidative stress.

Results: Radiographic scores, alkaline phosphatase levels, callus/diaphysis ratio, callus development, and bone mineral density were significantly lower in rats given HCQS at three and six weeks compared to the control group (p<0.005). When oxidative stress parameters were compared among the groups, all antioxidant parameters were statistically significant, indicating that antioxidant systems played a role in peripheral blood, when HCQS was used (p<0.005).

Conclusion: Oral HCQS intake impairs the fracture healing process by causing oxidative stress in rats. However, further biomolecular researches are needed to understand the underlying mechanism of these effects

Declarations

Ethics Committee Approval

All procedures were performed in the Experimental Animals Breeding and Research Center of the Kahramanmaraş Sütçü Imam University Faculty of Medicine, Türkiye. Animal care was carried out with the prior approval of the Sutcu Imam University Animal Experimental Ethics Committee on May 2020 with approval number 2020/05 and was in full compliance with Turkish Law 6343/2, Veterinary Medicine Deontology Regulation 6.7.26, and the Helsinki Declaration of Animal Rights.

Author Contributions

Idea/concept, data collection and/ or processing: D.T., K.G., F.D., E.K., E.B., P.G.; Design, literature review: D.T., K.G., A.E., Ö.B.; Control/supervision: Ö.B., A.E., E.K., E.B.; Writing the article: D.T., K.G., F.D.; Critical review: A.E., Ö.B., P.G.; References and fundings: D.T., F.D., K.G.; Materials: E.K., E.B., A.E.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

The authors are indebted to the Research Foundation of Kahramanmaraş Sütçü Imam University Faculty of Medicine (Project ID: 2020\4-14 M) for its financial support in this work.

Acknowledgments

The authors are indebted to the Research Foundation of Kahramanmaraş Sütçü Imam University Faculty of Medicine (Project ID: 2020\4-14 M) for its financial support in this work, special thanks to Prof. Dr. Atilla Yoldaş (Department of Anatomy, Kahramanmaraş Sütçü Imam University Faculty of Medicine) for his tireless assistance at surgical technique standardization and operative assistance thanks are also due to Mr. Onur Öztürk for his tireless assistance at photographs taken and transportation.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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