sirolimus and Burns--Chemical

sirolimus has been researched along with Burns--Chemical* in 5 studies

Other Studies

5 other study(ies) available for sirolimus and Burns--Chemical

ArticleYear
Rapamycin inhibits corneal inflammatory response and neovascularization in a mouse model of corneal alkali burn.
    Experimental eye research, 2023, Volume: 233

    Alkali burn-induced corneal injury often causes inflammation and neovascularization and leads to compromised vision. We previously reported that rapamycin ameliorated corneal injury after alkali burns by methylation modification. In this study, we aimed to investigate the rapamycin-medicated mechanism against corneal inflammation and neovascularization. Our data showed that alkali burn could induce a range of different inflammatory response, including a stark upregulation of pro-inflammatory factor expression and an increase in the infiltration of myeloperoxidase- and F4/80-positive cells from the corneal limbus to the central stroma. Rapamycin effectively downregulated the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), toll-like receptor 4 (TLR4), nucleotide binding oligomerization domain-like receptors (NLR) family pyrin domain-containing 3 (NLRP3), and Caspase-1, and suppressed the infiltration of neutrophils and macrophages. Inflammation-related angiogenesis mediated by matrix metalloproteinase-2 (MMP-2) and rapamycin restrained this process by inhibiting the TNF-α upregulation in burned corneas of mice. Rapamycin also restrained corneal alkali burn-induced inflammation by regulating HIF-1α/VEGF-mediated angiogenesis and the serum cytokines TNF-α, IL-6, Interferon-gamma (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The findings of this study indicated rapamycin may reduce inflammation-associated infiltration of inflammatory cells, shape the expression of cytokines, and balance the regulation of MMP-2 and HIF-1α-mediated inflammation and angiogenesis by suppressing mTOR activation in corneal wound healing induced by an alkali injury. It offered novel insights relevant for a potent drug for treating corneal alkali burn.

    Topics: Alkalies; Animals; Burns, Chemical; Cornea; Corneal Injuries; Corneal Neovascularization; Cytokines; Disease Models, Animal; Eye Burns; Inflammation; Matrix Metalloproteinase 2; Mice; Neovascularization, Pathologic; Sirolimus; Tumor Necrosis Factor-alpha

2023
Rapamycin ameliorates corneal injury after alkali burn through methylation modification in mouse TSC1 and mTOR genes.
    Experimental eye research, 2021, Volume: 203

    Alkali burn to the cornea is one of the most intractable injuries to the eye due to the opacity resulting from neovascularization (NV) and fibrosis. Numerous studies have focused on studying the effect of drugs on alkali-induced corneal injury in mouse, but fewer on the involvement of alkali-induced DNA methylation and the PI3K/AKT/mTOR signaling pathway in the mechanism of alkali-induced corneal injury. Thus, the aim of this study was to determine the involvement of DNA methyltransferase 3 B-madiated DNA methylation and PI3K/AKT/mTOR signaling modulation in the mechanism of alkali-induced corneal injury in a mouse model. To this end, we used bisulfite sequencing polymerase chain reaction and Western blot analysis, to study the effects of 5-aza-2'-deoxycytidine and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, which inhibit methyltransferase and PI3K respectively, on DNA methylation and expression of downstream effectors of PI3K related to corneal NV, including TSC1 and mTOR genes. The results showed that, after an intraperitoneal injection of rapamycin (2 mg/kg/day) for seven days, the alkali-induced opacity and NV were remarkably decreased mainly by suppressing the infiltration of immune cells into injured corneas, angiogenesis, VEGF expression and myofibroblasts differentiation; as well as by promoting corneal cell proliferation and PI3K/AKT/mTOR signaling. More significantly, these findings showed that epigenetic regulatory mechanisms by DNA methylation played a key role in corneal NV, including in corneal alkali burn-induced methylation modification and rapamycin-induced DNA demethylation which involved the regulation of the PI3K/AKT/mTOR signaling pathway at the protein level. The precise findings of morphological improvement and regulatory mechanisms are helpful to guide the use of rapamycin in the treatment of corneal angiogenesis induced by alkaline-burn.

    Topics: Actins; Animals; Blotting, Western; Burns, Chemical; Chromones; Corneal Injuries; Disease Models, Animal; DNA Methylation; Eye Burns; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation; Immunosuppressive Agents; Male; Mice; Morpholines; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Sirolimus; Sodium Hydroxide; TOR Serine-Threonine Kinases; Tuberous Sclerosis Complex 1 Protein; Vascular Endothelial Growth Factor A

2021
Nanostructured lipid carriers containing rapamycin for prevention of corneal fibroblasts proliferation and haze propagation after burn injuries: In vitro and in vivo.
    Journal of cellular physiology, 2019, Volume: 234, Issue:4

    Topics: Administration, Ophthalmic; Animals; Burns, Chemical; Cell Proliferation; Cells, Cultured; Cornea; Corneal Injuries; Corneal Neovascularization; Corneal Opacity; Disease Models, Animal; Drug Carriers; Drug Compounding; Eye Burns; Fibroblasts; Fibrosis; Humans; Lipids; Male; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Sirolimus; Sodium Hydroxide; Wound Healing

2019
Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-β1/ERK pathways regulation.
    Investigative ophthalmology & visual science, 2013, Jul-02, Volume: 54, Issue:7

    To investigate the protective effect of rapamycin against alkali burn-induced corneal damage in mice.. BALB/c mice were treated with 0.1 N NaOH to the cornea for 30 seconds. Corneal neovascularization and opacity were clinically evaluated at 1, 2, and 4 weeks after chemical burn injury. Rapamycin was delivered topically to right eyes (1 mg/mL) and injected intraperitoneally (0.2 mg/kg) once a day. Concentrations of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-β1) in the cornea were measured by enzyme-linked immunosorbent assay (ELISA). In vitro-cultured human corneal stromal cells were treated with 0 to 500 nM rapamycin for 3 days and then assessed by immunofluorescence staining of vimentin and alpha-smooth muscle actin (α-SMA). Western blotting assays for α-SMA, phosphorylated extracellular signal-regulated kinase (ρ-ERK 1/2), and total ERK 1/2 were also performed.. Corneal neovascularization and corneal opacity scores measured 4 weeks after the chemical burn corneal injury were lower in the rapamycin group than in the control group. Two weeks after the chemical burn injury, a significant elevation in the corneal IL-6 levels of the positive control group was observed, compared to the levels in the negative control group or the rapamycin group (P < 0.05). Corneal TGF-β1 levels were lower in the rapamycin-treated group than in the control group at 4 weeks after chemical burn injury (P < 0.05). Moreover, rapamycin inhibited TGF-β1-induced α-SMA expression and augmented ERK 1/2 phosphorylation.. Rapamycin treatment reduced corneal opacity and corneal neovascularization in BALB/c mice. Rapamycin protected the cornea from chemical damage via reduction of IL-6 and TGF-β1 expression. Rapamycin reduced α-SMA expression through the ERK 1/2 pathway.

    Topics: Animals; Blotting, Western; Burns, Chemical; Cells, Cultured; Corneal Neovascularization; Corneal Opacity; Corneal Stroma; Enzyme-Linked Immunosorbent Assay; Eye Burns; Immunosuppressive Agents; Injections, Intraperitoneal; Interleukin-6; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Signal Transduction; Sirolimus

2013
Combined treatment with antioxidants and immunosuppressants on cytokine release by human peripheral blood mononuclear cells - chemically injured keratocyte reaction.
    Molecular vision, 2011, Volume: 17

    To investigate the effect of antioxidants and immunosuppresants on mixed peripheral blood mononuclear cells (PBMC) - chemically injured keratocytes reaction (MLKR).. The PBMC stimulation assay was performed using chemically injured keratocytes treated with 0.05 N NaOH for 90 s (MLKR). MLKR were treated with various drugs including rapamycin, dexamethasone, mycophenoleic acid (MPA), alpha lipoic acid (ALA), and N-acetyl cysteine (NAC). Matrix metalloprotease-9 (MMP-9), transforming growth factor-beta 1 (TGF-β1), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF) secretion profiles of activated PBMCs stimulated by NaOH-treated keratocytes were determined by ELISA.. Anti-oxidants as well as immunosuppressants suppressed PBMC proliferation. MMP-9 levels were lower in antioxidants group. IL-6 levels decreased in dexamethasone group and anti-oxidants group. Combination of immunosuppressants and antioxidants suppressed more PBMC proliferation except for rapamycin + ALA group, suppressed MMP-9 production except for MPA + ALA group, decreased IL-6 levels and increased MIF levels except for rapamycin + ALA group. TGF-β1 levels were elevated in rapamycin group and rapamycin + ALA group.. Cytokine production was different depending on combination of drugs.Our results suggest that the different drugs should be selected for treatment according to the phases of corneal chemical burn.

    Topics: Acetylcysteine; Antioxidants; Burns, Chemical; Cells, Cultured; Coculture Techniques; Cornea; Corneal Injuries; Corneal Keratocytes; Dexamethasone; Drug Combinations; Humans; Immunosuppressive Agents; Interleukin-6; Intramolecular Oxidoreductases; Leukocytes, Mononuclear; Macrophage Migration-Inhibitory Factors; Matrix Metalloproteinase 9; Mycophenolic Acid; Sirolimus; Sodium Hydroxide; Thioctic Acid; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

2011