دورية أكاديمية
أعرض في EDS

Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model.

التفاصيل البيبلوغرافية
العنوان: Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model.
المؤلفون: Siregar O; Department of Orthopaedics and Traumatology, Adam Malik General Hospital, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia., Lelo A; Department of Pharmacology and Therapeutics School of Medicine, Universitas Sumatera Utara, Indonesia., Rahyussalim AJ; Department of Orthopaedics and Traumatology, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Ilyas S; Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia., Benny; Department of Orthopaedics and Traumatology, Adam Malik General Hospital, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia., Kurniawati T; Stem Cell and Tissue Engineering Cluster, IMERI Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.; Stem Cell Medical Technology Integrated Service Unit, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia., Augustinus Y; Department of Orthopaedics and Traumatology, Adam Malik General Hospital, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia., Hendra; Department of Orthopaedics and Traumatology, Adam Malik General Hospital, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia., Mandagi T; Department of Orthopaedics and Traumatology, Adam Malik General Hospital, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia., Zufar MLL; Medical graduate, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Fathurrahman I; Medical graduate, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
المصدر: BioMed research international [Biomed Res Int] 2023 Jan 27; Vol. 2023, pp. 7421325. Date of Electronic Publication: 2023 Jan 27 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Hindawi Pub. Co.
مواضيع طبية MeSH: Doxycycline*/pharmacology , Spondylitis*/drug therapy , Tuberculosis*/microbiology , Matrix Metalloproteinase Inhibitors*/pharmacology, Animals ; Humans ; Rabbits ; Matrix Metalloproteinase 1/metabolism ; Mycobacterium tuberculosis
مستخلص: Background: Tuberculosis (TB) of the spine is a highly disruptive disease, especially in underdeveloped and developing countries. This condition requires standard TB treatment for 9-18 months, which increases patient risk of drug-resistant TB. Consequently, this raises the concern of adopting additional therapies to shorten the treatment duration, improve the efficacy of anti-TB drugs, and further decrease damage in the affected tissues and organs. Matrix metalloproteinase- (MMP-) 1 is a key regulator of the destruction of the extracellular matrix and associated proteins and is a new potential target for TB treatment research. In the present study, we investigated the effects of doxycycline as an MMP-1 inhibitor in patients with spondylitis TB.
Methods: Seventy-two New Zealand white rabbits with spondylitis TB were divided into 12 different groups based on incubation period (2, 4, 6, and 8 weeks) and doxycycline administration (without, 1 mg/kg body weight (BW), and 5 mg/kg BW). We observed the course of infection through the blood concentration changes and immunohistochemical examination of MMP-1, in addition to BTA staining, culture, polymerase chain reaction (PCR), and histopathological examination.
Results: Treatment with once daily 5 mg/kg BW doxycycline significantly improved the blood MMP-1 level ( p < 0.05) compared with the placebo and 1 mg/kg BW doxycycline. A significantly reduced ongoing infection and a higher healing rate were demonstrated in rabbits with a higher doxycycline dose through BTA staining, culture, PCR, and histopathology. Various degrees of vertebral endplates, vertebral body, and intervertebral disc destruction were observed in 32 rabbits with positive histopathological findings, in addition to positive inflammatory cell infiltration, characterized by numerous lymphocytes, macrophages, and epithelial cells, as well as abundant granulation tissue and necrotic substances proximal to the inoculated vertebral area. Bone and intervertebral disc destructions were more apparent in the untreated rabbits.
Conclusion: Our study demonstrated the potential of doxycycline as an adjunctive treatment in spondylitis TB. However, limitations remain regarding the differences in the pathogenesis and virulence of Mycobacterium tuberculosis between rabbit and human systems, sample size, and the dose-dependent effect of doxycycline. Further studies are needed to address these issues.
Competing Interests: The authors declare no conflicts of interest regarding the research, authorship, and/or publication of this article.
(Copyright © 2023 Otman Siregar et al.)
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المشرفين على المادة: N12000U13O (Doxycycline)
EC 3.4.24.7 (Matrix Metalloproteinase 1)
0 (Matrix Metalloproteinase Inhibitors)
تواريخ الأحداث: Date Created: 20230206 Date Completed: 20230209 Latest Revision: 20230209
رمز التحديث: 20230210
مُعرف محوري في PubMed: PMC9897918
DOI: 10.1155/2023/7421325
PMID: 36743515
قاعدة البيانات: MEDLINE
الوصف
تدمد:2314-6141
DOI:10.1155/2023/7421325