Disulfiram ameliorates bleomycin induced pulmonary inflammation and fibrosis in rats.

Bleomycin (BL) is a widely used anticancer drug that can cause pulmonary fibrosis due to increased fibroblast proliferation and increased secretion of extracellular matrix. RASSF1A is a tumor suppressor gene that is down-regulated by DNA methylation during fibrosis. Disulfiram (DSF), a noncytosine DNA methyltransferase inhibitor, can revert epigenetic biomarkers and re-express silenced genes. We investigated anti-inflammatory and anti-fibrotic effects of DSF on regulation of epigenetic molecules and histopathology in a rat model of BL induced pulmonary fibrosis. We used six groups of rats: sesame oil (SO) control (Co) group, BL group, BL + SO group and three BL + DSF groups administered 1 mg/kg DSF (BL + DSF), 10 mg/kg DSF (BL + DSF10) or 100 mg/kg DSF (BL + DSF100), respectively. BL was administered intratracheally to induce pulmonary fibrosis. DSF and SO were injected intraperitoneally (i.p.) 2 days before BL administration; these injections were continued for 3 weeks. At the end of the study, lung tissues were removed for molecular and histopathologic studies. Administration of 10 or 100 mg/kg DSF after BL induced pulmonary inflammation and fibrosis, and up-regulated RASSF1A and down-regulated TNF-α and IL-1 ß compared to the BL and BL + SO groups. A RASSF1A unmethylated band was observed using the methylation-specific PCR technique in rats that had been administered 10 and 100 mg/kg DSF, which indicated partial DNA demethylation. Histopathologic evaluation revealed that fibrosis and all inflammatory scores were decreased significantly in the BL + DSF10 and BL + DSF100 groups compared to the BL group. Our findings indicate that DSF modified DNA methylation by up-regulating RASSF1A, which reduced inflammation and fibrosis in BL induced pulmonary inflammation and fibrosis.

N-Acetylcysteine attenuated pulmonary fibrosis induced by bleomycin via immunomodulation responses.

Background and purpose: Pulmonary fibrosis (PF) is a chronic and life-threatening interstitial lung disease. N-acetyl cysteine (NAC) is an antioxidant pharmaceutically available to reduce endothelial dysfunction, inflammation, and fibrosis, however, the therapeutic effect of NAC on PF has not been clearly identified. This research aimed to investigate the possible therapeutic impact of NAC on PF induced by bleomycin in the rat model. Experimental approach: Rats received intraperitoneal injections of NAC at 150, 300, and 600 mg/kg for 28 days before bleomycin, while the positive and negative control groups were treated with bleomycin alone and normal saline, respectively. Then, rats' lung tissues were isolated and leukocyte infiltration and also collagen deposition were evaluated using hematoxylin and eosin and Mallory trichrome stainings, respectively. In addition, the levels of IL-17, and TGF-ß cytokines in bronchoalveolar lavage fluid and hydroxyproline in homogenized lung tissues were assayed using the ELISA method. Findings/Results: Histological findings indicated that NAC decreased leukocyte infiltration, collagen deposition, and fibrosis score in the bleomycin-induced PF tissue. Moreover, NAC significantly reduced TGF-ß and hydroxyproline levels at 300-600 mg/kg, as well as IL-17 cytokine at 600 mg/kg. Conclusion and implications: NAC showed a potential anti-fibrotic effect by reducing hydroxyproline and TGF-ß as well as an anti-inflammatory effect by decreasing IL-17 cytokine. So, it may be administered as a prophylactic or therapeutic candidate agent to attenuate PF via immunomodulatory effects. Although, future studies are suggested.

Regioselective alkylation of 2,4-dihydroxybenzyaldehydes and 2,4-dihydroxyacetophenones.

We report a cesium bicarbonate-mediated alkylation of 2,4-dihydroxybenzyaldehyde and 2,4-dihydroxyacetophenone to generate 4-alkylated products in acetonitrile at 80 °C with excellent regioselectivity, up to 95% isolated yields, and broad substrate scope.

Cellulose matrix embedded copper decorated magnetic bionanocomposite as a green catalyst in the synthesis of dihydropyridines and polyhydroquinolines.

A new biopolymer-based magnetic nanocomposite was prepared and characterized by Fourier transform infrared (FT-IR) spectroscopy, energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images, inductively-coupled plasma atomic emission spectroscopy (ICP-AES) analysis, thermogravimetric/differential thermal (TG/DT) analysis and atomic force microscopy (AFM) image analysis. Then, it was applied as an efficient heterogeneous catalyst in two important three- and four-component one-pot organic condensation reactions for the synthesis of Hantzsch 1,4-dihydropyridine and polyhydroquinoline derivatives in high yields under solvent-free condition at room temperature. The first design and development of a low-leaching bionanostructure, easy separation and reusability of the nanocatalyst, simple work-up procedure, mild, green and environmentally friendly conditions are some important features and advantages of the present work.