title: Benzanthrone induced immunotoxicity via oxidative stress and inflammatory mediators in Balb/c mice.
abstract: Benzanthrone (BA) is an important dye intermediate which is used in the manufacturing of several polycyclic vat and disperse dyes in textile industries. Several studies have indicated that the general population is also exposed to BA owing to its release from furnace effluents and automobile exhausts in the environment. In several clinical studies, it has been shown that workers exposed to BA developed itching, burning sensation, erythema and hyperpigmentation of the skin, which could be an outcome of the dysregulated immune response. In this study, we have used female Balb/c mice as a model to study the immuno-inflammatory changes after systemic administration of BA (7.5mg/kgb.w. and 15mg/kgb.w.) for one week. BA exposed animals exhibited the signs of intense systemic inflammation as evident by enhanced DTH response, MPO activity, hyperplastic and dysplastic histopathological organization of spleen and lung tissue. Splenic evaluation revealed enhanced oxidative stress, upregulation of prominent inflammatory markers like iNOS and COX-2 and DNA damage. In coherence with the observed immuno-inflammatory alterations, the levels of several inflammatory and regulatory cytokines (IL-17, TNF-α, IFN-γ, IL-1, IL-10, IL-4) were significantly enhanced in serum as well as the spleen. In addition, BA administration significantly induced the activation of ERK1/2, p38, JNK MAPKs and their downstream transcription factors AP-1 (c-fos, c-jun), NF-κB and Nrf2 which comprise important mechanistic pathways involved in inflammatory manifestations. These results suggest the immunotoxic nature of the BA and have implications for the risk assessment and management of occupational workers, and even common masses considering its presence as an environmental contaminant.
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Tewari
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Roy
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Payal
authors.initials: P
authors.lastname: Mandal
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Yadav
authors.affiliation: Pathology Laboratory, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001, India.
authors.forename: Bhushan P
authors.initials: BP
authors.lastname: Chaudhari
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), New Delhi, India; Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, India.
authors.forename: Rajnish K
authors.initials: RK
authors.lastname: Chaturvedi
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Premendra D
authors.initials: PD
authors.lastname: Dwivedi
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India. Electronic address: anurag1706@gmail.com.
authors.forename: Anurag
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Food, Drugs and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: mditrc@rediffmail.com.
authors.forename: Mukul
authors.initials: M
authors.lastname: Das
mesh_terms: D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D016273:Occupational Exposure / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001551:Benz(a)Anthracenes; D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; C012768:benzanthrone
keywords: Antioxidant enzyme; Benzanthrone; Cytokine; DNA damage; Immunotoxicity; Inflammation; Reactive oxygen species