title: Protective and therapeutic effect of apocynin on bleomycin-induced lung fibrosis in rats.
abstract: We aimed to investigate the preventive and therapeutic effect of apocynin (APO) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; APO group, 20 mg/kg APO was given intraperitoneal for 29 days; BLC-1 and BLC-2 groups, a single intratracheal injection of BLC (2.5 mg/kg); APO+BLC-preventive group, 20 mg/kg APO was administered 12 h before the intratracheal BLC injection and continued for 14 days; BLC+APO-treatment group, 20 mg/kg APO was given on the 14th day after the intratracheal BLC injection and continued to sacrifice. The BLC-1 group was sacrificed on the 14th day of BLC administration to validate BLC-induced lung inflammation and fibrosis on the 14th of study initiation. All other groups were sacrificed on the 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity, total oxidant status (TOS), and oxidative stress index (OSI) were measured. An addition to the serum myeloperoxidase (MPO), the cell count and cytokines (IL-1β, IL-6, and IL-8) of bronchoalveolar lavage (BAL) fluid were assayed. BLC-provoked histological changes were significantly detected compared to the control group. APO restored these histological damages in different quantity in the treatment and prevention groups. BLC caused a significant decrease in GSH, CAT, and GPX, which were accompanied with significantly the increased MDA, TOS levels, and OSI in the lung tissue concomitant with increased levels of the cellular account and proinflammatory cytokines in the BAL fluid. Otherwise, APO administration, both before and after BLC, reversed all biochemical markers and cytokine as well as histopathological changes induced by BLC. Interestingly, APO treatment reversed MPO activity in serum increased by BLC. In this study, both protective and therapeutic effects of APO against BLC-induced lung fibrosis were demonstrated for the first time.
authors.affiliation: Department of Pulmonary Medicine, Inonu University Faculty of Medicine, Malatya, Turkey, talatkilic2013@gmail.com.
authors.forename: Talat
authors.initials: T
authors.lastname: Kilic
authors.forename: Hakan
authors.initials: H
authors.lastname: Parlakpinar
authors.forename: Elif
authors.initials: E
authors.lastname: Taslidere
authors.forename: Sedat
authors.initials: S
authors.lastname: Yildiz
authors.forename: Alaadin
authors.initials: A
authors.lastname: Polat
authors.forename: Nigar
authors.initials: N
authors.lastname: Vardi
authors.forename: Cemil
authors.initials: C
authors.lastname: Colak
authors.forename: Hilal
authors.initials: H
authors.lastname: Ermis
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000097:blood; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D015415:Biomarkers; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D001761:Bleomycin; D008315:Malondialdehyde; C056165:acetovanillone; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione