title: Diallyl sulfide attenuates bleomycin-induced pulmonary fibrosis: critical role of iNOS, NF-kappaB, TNF-alpha and IL-1beta.
abstract: Diallylsulfide (DAS), an antioxidant and anti-inflammatory agent was evaluated for its ability to repress lung fibrosis induced by bleomycin in Wistar rats. A single intra tracheal administration of bleomycin (6.5 U/kg BW) was administered to pulmonary fibrosis group, while DAS (120 mg/kg BW) was administered intraperitoneally throughout the experimental period. Fibrotic changes in the lungs were estimated by measuring lung hydroxyproline content. Bleomycin administration significantly (P<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the lung tissues. Bleomycin caused a significant decrease in the level of reduced glutathione (GSH), which was accompanied with significant increase in lipid peroxidation (LPO) level, and myeloperoxidase (MPO) activity, in the lung tissues. An increase in the level of cell counts in bronchoalveolar lavage fluid (BALF) was observed in bleomycin induced group. DAS administration altered the levels of enzymic antioxidants, TBARS, MPO and GSH towards normal values. Histopathological analysis and picrosirius red staining showed an increased collagen deposition in rats receiving bleomycin alone that was decreased upon DAS treatment. Immunohistochemical studies revealed that DAS reduced the bleomycin-induced activation of inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-kappaB) and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), in the lung tissues. The present study provides evidence that DAS might serve as a novel target for the therapeutic treatment of lung fibrosis.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy campus, Chennai, 600 025, Tamil nadu, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Kalayarasan
authors.forename: Narayanan
authors.initials: N
authors.lastname: Sriram
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000498:Allyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D053583:Interleukin-1beta; D016328:NF-kappa B; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C038491:allyl sulfide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat