The Role of Doxycycline as a Matrix Metalloproteinase Inhibitor for the Treatment of Chronic Wounds

Stechmiller, Joyce; Cowan, Linda; Schultz, Gregory S.

doi:10.1177/1099800409346333

Cited by 91 publications

(67 citation statements)

References 56 publications

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“…Doxycycline can also impact the gut microbiota in humans; the direct impact of this on adipose biology is unclear but potentially significant (Angelakis et al 2014). Furthermore, doxycycline can regulate the function of matrix metalloproteinases (Stechmiller et al 2010). Nevertheless, we are presently unaware of data that would suggest that short-term doxycycline exposure directly impacts adipose tissue turnover in a manner that would confound lineage tracing studies.…”

Section: Perspectives Limitations and Future Directionsmentioning

confidence: 99%

Sorting out adipocyte precursors and their role in physiology and disease

2017

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The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear. Recent studies have identified distinct adipocyte precursor populations that are physiologically regulated and contribute to the development, maintenance, and expansion of adipocyte pools in mice. With new tools available, the properties of adipocyte precursors can now be defined, and the regulation and function of adipose plasticity in development and physiology can be explored.Adipocytes ("fat cells") are critical regulators of several aspects of normal physiology, including energy balance, nutrient homeostasis, and tissue homeostasis (Rosen and Spiegelman 2014). White adipocytes represent the principle site for energy storage in mammals. These cells accumulate excess energy in the form of intracellular triglycerides packaged into large single lipid droplets. White adipocytes are also endocrine cells; adipocytes secrete numerous hormones and cytokines that impact several aspects of physiology, including nutrient homeostasis, inflammation, and reproductive biology (Ouchi et al.

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Section: Perspectives Limitations and Future Directionsmentioning

confidence: 99%

Sorting out adipocyte precursors and their role in physiology and disease

2017

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“…Doxycycline has been experimentally shown to reduce tissue degradation (Bildt et al, 2009;Li et al, 2013) and its activity as an MMP inhibitor makes it attractive as a potential treatment for chronic wounds (Naidoo et al, 2009;Stechmiller et al, 2010). The MMP inhibitory action of doxycycline is independent of its antimicrobial properties and thus unrelated to its inhibitory effect on bacterial protein synthesis.…”

Section: Introductionmentioning

confidence: 99%

“…Although the full mechanism has yet to be elucidated, it is believed to inhibit enzymatic MMP activity through the chelation of the zinc molecule and MMP gene expression (Li et al, 2013). Doxycycline's inhibitory activity extends to TNFa-converting enzyme (TACE), a molecule that causes release of tumor necrosis factor-alpha (TNFa), which is an important inflammatory mediator known to impair wound healing (Stechmiller et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity

Omolu

Bailly²,

Day

2017

Drug Delivery

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Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-M TM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750 lm). Treatment of Strat-M TM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-M TM . Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds. ARTICLE HISTORY

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“…Tetrasiklinler ve KMT'lerin nötrofil, sitokin ve MMP'leri inhibe edebilme özelliğine bağlı olarak yara iyileşmesini hızlandırdıkları bildirilmiştir. Ayrıca topikal doksisiklin MMP inhibisyonu ile yara iyileşmesini hızlandırdığı gösterilmiştir [24] . Kaposi sarkomunda MMP-2 ve MMP-9 düzeylerinde artış olması üzerine KMT-3 ile faz 2 çalışma sonuçlarında anlamlı olmasa da tetrasiklinlerin etkili olduğu gösterilmiş, tetrasiklin tedavisi ile MMP-2 ve MMP-9 seviyelerinin anlamlı olarak azaldığı gösterilse de, MMP inhibitörleri ile yapılan çalışmalar sonuçsuz kalmıştır [25,26] .…”

Section: Anti-enflamatuvar Etkiunclassified

Non Antimicrobial Effects of Antibacterial Agents

Demiraslan¹,

Uysal²

2018

mjima

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Aside from their antibacterial activity, antimicrobial agents have also some beneficial effects due to their chemical structures. These effects include anti-inflammatory, immunomodulatory, anti-cancer, anti-angiogenic, neuroprotective, cardioprotective, augmented gastrointestinal motility, and binding toxins. This paper does not comprise non-antimicrobial effects of all antibiotics due to the fact that the issue is very extended. We reviewed use of penicillins in mushroom poisoning and their promising inhibitor effect on proliferation of cervical carcinoma and leukemia cells. We summarized neuroprotective effect of ceftriaxone and its inhibitory potential on proliferation of lung cancer cells. Tetracyclines are agents that have been focused on and investigated for a long time, and demeclocycline that belongs to this group is used for inappropriate antidiuretic hormone secretion. Moreover, low-dose doxycycline that is also a tetracycline, has been approved for the treatment of periodontitis, and inhibition of matrix metalloproteinase enzyme is the responsible mechanism for its anti-inflammatory action. Matrix metalloproteinase inhibition also provides a decrease in tumor angiogenesis and metastasis. Minocycline, another tetracycline, reduces the synthesis of beta-amyloid which plays a key role in Alzheimer's disease and other neurodegenerative diseases, and it also inhibits glial inducible nitric oxide (NO) synthase and NOmediated neurotoxicity. Erythromycin that is a macrolide antibiotic is used as a gastrointestinal motility augmenter; azithromycin gives an early improvement in patients with cystic fibrosis due to its anti-inflammatory effect. It has been shown that clarithromycin decreases the metastatic AbstractAntimikrobiyal ajanlar kimyasal yapılarından dolayı bakterilere karşı aktiviteleri dışında bazı yararlı etkilere de sahiptirler. Bunlar arasında antienflamatuvar, immünomodülatör, anti-kanser, anti-anjiyogenik, nöroprotektif, kardiyoprotektif, gastrointestinal hareket artırıcı ve toksin bağlayıcı etkiler sayılabilir. Bu yazıda, konu çok geniş olduğundan dolayı sınırlı sayıda antibiyotiğin antimikrobiyal dışı etkileri ele alınmıştır. Penisilinlerin serviks ve lösemik kanser hücrelerinin çoğalmasını durdurma konusunda ümit vaat edici etkisi ve mantar zehirlenmesi tedavisinde kullanımı; seftriaksonun akciğer kanseri hücreleri üzerindeki çoğalmayı önleyici potansiyeli ve nöroprotektif etkisi derlenmiştir. Tetrasiklinler uzun süredir üzerinde durulan ve araştırılan ajanlardır ve bu gruptaki demeklosiklin, uygunsuz antidiüretik hormon salınımında kullanılmaktadır. Ayrıca tetrasiklinlerden doksisiklin düşük dozda periodontit tedavisi için onay almıştır ve anti-enflamatuvar etkiden sorumlu mekanizma matriks metalloproteinaz (MMP) enzimi inhibisyonudur. Ayrıca MMP inhibisyonu metastazda ve tümör anjiyogenezinde azaltma da sağlayabilmektedir. Diğer bir tetrasiklin olan minosiklin ise Alzheimer ve diğer nörodejeneratif hastalıklarda kilit rolü olan beta-amilod sentezini azaltmakta ve ayrıca gliyal indüklenebilir ...

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The Role of Doxycycline as a Matrix Metalloproteinase Inhibitor for the Treatment of Chronic Wounds

Cited by 91 publications

References 56 publications

Sorting out adipocyte precursors and their role in physiology and disease

Sorting out adipocyte precursors and their role in physiology and disease

Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity

Non Antimicrobial Effects of Antibacterial Agents

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