Evaluation of role of doxycycline (a matrix metalloproteinase inhibitor) on renal functions in patients of diabetic nephropathy

Aggarwal, Hari Krishan; Jain, Deepak; Talapatra, Paulomi; Yadav, Raj Kumar; Gupta, Tulika; Kathuria, Kashmiri Lal

doi:10.3109/0886022x.2010.502606

Cited by 36 publications

(24 citation statements)

References 25 publications

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“…Furthermore, doxycyline at 2.0 mg/kg attenuates lung injury induced by LPS, doxycycline-resistant S. pneumoniae and bleomycin; and reduces inflammation in a model of asthma [4,5,14]. In humans, doxycycline has been used in the treatment of lymphangioleiomyomatosis (LAM) [15,16] and decreases proteinuria in diabetic nephropathy [17], although it was found to have no effect in osteoarthritis [18]. Clearly, doxycycline has anti-inflammatory properties that are independent of its antimicrobial activity.…”

Section: Discussionmentioning

confidence: 99%

Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide

et al. 2012

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BackgroundTetracyclines are broad-spectrum antibiotics that are also used to induce gene expression using the reverse tetracycline transactivator / tetracycline operator system (rtTA/tetO system). The system assumes that tetracyclines have no effects on mammals. However, a number of studies suggest that tetracyclines may have powerful anti-inflammatory effects. We report that the tetracycline, doxycycline, inhibits neutrophil (PMN) influx into the lungs of mice treated with bacterial endotoxin (LPS).MethodsMice were challenged with intratracheal LPS in the presence or absence of doxycyline. bronchoalveolar lavage cell counts and differential, total bronchoalveolar lavage protein, lung homogenate caspase-3 and tissue imaging were used to assess lung injury. In addition, PMN chemotaxis was measured in vitro and syndecan-1 was measured in bronchoalveolar lavage fluid.ResultsThe administration of doxycycline resulted in a significant decrease in the number of bronchoalveolar lavage PMNs in LPS-treated mice. Doxycycline had no effect on other markers of lung injury such as total bronchoalveolar lavage protein and whole lung caspase-3 activity. However, doxycycline resulted in a decrease in shed syndecan-1 in bronchoalveolar lavage fluid.ConclusionWe conclude that doxycycline has an important anti-inflammatory effect that can potentially confound the experiments in which the rtTA/tetO system is being used to study the immune response.

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Section: Discussionmentioning

confidence: 99%

Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide

et al. 2012

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“…Aggarwal et al demonstrated that compared with angiotensin-converting enzyme inhibitors (ACEIs) and or angiotensin receptor blockers (ARBs), doxycycline (an inhibitor of MMP) can effectively reduce proteinuria in adult patients with DN, but unfortunately it is effective only for a short duration, i.e. , less than 12 weeks [143]. …”

Section: Mmps and Diabetic Nephropathymentioning

confidence: 99%

“…MMP9 is another protease which has been investigated with respect to its role in the DN with mixed variable results and contradictions. It is of interest to note that non-specific pharmacological inhibition of MMP9 with doxycycline were found to be associated with amelioration of renal injury [143]. In addition, it is also reported that Simvastatin protects kidney damage of diabetic rat through the suppression of MMP9 expression [147].…”

Section: Mmps and Diabetic Nephropathymentioning

confidence: 99%

A Glimpse of Matrix Metalloproteinases in Diabetic Nephropathy

Xiao

et al. 2014

CMC

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Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic nephropathy, which not only is related to the excessive synthesis of matrix proteins, but also to their decreased degradation by the MMPs. In recent years, increasing evidence suggest that there is a good correlation between the activity or expression of MMPs and progression of renal disease in patients with diabetic nephropathy in humans and in various experimental animal models. In such a diabetic milieu, the expression of MMPs is modulated by high glucose, advanced glycation end products (AGEs), TGF-β, reactive oxygen species (ROS), transcription factors and some of the microRNAs. In this review, we focused on the structure and functions of MMPs, and their role in the pathogenesis of diabetic nephropathy.

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“…The mechanism remains unclear. [189] [190][191][192][193][194][195][196] MMP-plays important role in development of diabetic nephropathy. [193,194] Dysregulation in NGAL, MMP-9 aand MMP2 is noted in type1 diabetes.…”

Section: Mechanismmentioning

confidence: 99%