title: Alleviation of lung injury by glycyrrhizic acid in benzo(a)pyrene exposed rats: Probable role of soluble epoxide hydrolase and thioredoxin reductase.
abstract: Benzo(a)pyrene [B(a)P] is known to alter lung physiology by interfering in various intracellular pathways including alterations in NF-κB activities, cytokine release and cell survival. NF-κB suppression/activation plays a major role in cell survival status. Present investigation deals with such kind of effects of B(a)P on lungs in relation with soluble epoxide hydrolase (sEH) and thioredoxin reductase (TrxR) activities. Glycyrrhizic acid (GA), an active principle of Glycyrrhiza glabra (Licorice), is known to modulate various molecular processes. In the present study, we investigated the protective effects of GA against B(a)P induced debilities in lungs of Wistar rats. Intratracheal instillation of B(a)P significantly suppressed NF-κB translocation, sEH, TrxR and catalase activities in lung tissue. A marked induction of H(2)O(2) levels along with caspases activation (caspases-2, -3, -6, -8, and -9) in lung tissue after B(a)P exposure was observed. Lung injury was assessed by measuring lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total cell count, total protein, neutrophil elastase activity in bronchoalveolar lavage fluid (BALF). Reduction in phospholipid content further potentiated these parameters. GA oral administration (50 and 100mg/kg b.wt.) significantly showed protection of lung epithelium by suppression of caspases activities in lung tissue and reduction of total protein, total cells, elastase activity, LDH and ALP activities along with fortification of phospholipids in BALF. Histological observations also confirm the findings in above mentioned parameters. Results indicate a strong correlation between amelioration of sEH and TrxR activities, and NF-κB activation. The present investigation gives an insight into probable mechanisms of lung injuries induced by short term exposures of B(a)P and prevention by glycyrrhizic acid.
authors: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors: Wajhul
authors: W
authors: Qamar
authors: Rehan
authors: R
authors: Khan
authors: Abdul Quaiyoom
authors: AQ
authors: Khan
authors: Muneeb U
authors: MU
authors: Rehman
authors: Abdul
authors: A
authors: Lateef
authors: Mir
authors: M
authors: Tahir
authors: Farrah
authors: F
authors: Ali
authors: Sarwat
authors: S
authors: Sultana
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D007202:Indicators and Reagents; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D010743:Phospholipids / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004785:Environmental Pollutants; D007202:Indicators and Reagents; D016328:NF-kappa B; D010743:Phospholipids; D001564:Benzo(a)pyrene; D019695:Glycyrrhizic Acid; D007770:L-Lactate Dehydrogenase; D013880:Thioredoxin-Disulfide Reductase; D000469:Alkaline Phosphatase; D004851:Epoxide Hydrolases; D019272:Leukocyte Elastase; D020169:Caspases