Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model.
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 additi...
| Publicado en: | BioMed Research International pp. 1 - 13 |
|---|---|
| Autores principales: | , , , , , , , , , , |
| Formato: | diagnostic images pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
1/27/2023
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=161547200&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 161547200 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 1/27/2023 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 161547200 161547200 161547200 10.1155/2023/7421325 161547200 ppf: 1 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Doxycycline as a Potential MMP-1 Inhibitor for the Treatment of Spondylitis Tuberculosis: A Study in Rabbit Model. aug: au: Siregar, Otman Lelo, Aznan Rahyussalim, Ahmad Jabir Ilyas, Syafruddin Benny Kurniawati, Tri Augustinus, Yohanes Hendra Mandagi, Tommy Zufar, Muhammad Luqman Labib Fathurrahman, Irfan affil: Department of Orthopaedics and Traumatology, Adam Malik General Hospital, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia sug: subj: Tuberculosis, Spinal Drug Therapy Doxycycline Pharmacodynamics Antibiotics, Antitubercular Pharmacodynamics Matrix Metalloproteinases Antagonists and Inhibitors Spondylitis, Ankylosing Animal Studies Rabbits Drug Resistance, Multiple Immunohistochemistry Vertebral Body Pathology Polymerase Chain Reaction Mycobacterium Tuberculosis Analysis Matrix Metalloproteinases Drug Effects Matrix Metalloproteinases Blood Doxycycline Administration and Dosage ab: 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. pubtype: Academic Journal doctype: diagnostic images pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|