4.7 Article

Regulation of inflammation and COX-2 gene expression in benzo (a) pyrene induced lung carcinogenesis in mice by all trans retinoic acid (ATRA)

Journal

LIFE SCIENCES
Volume 285, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119967

Keywords

ATRA; COX-2; B(a)P induced mice-lung cancer; Inflammation marker; Haematology; RT-PCR/qPCR

Funding

  1. Department of Science and Technology, SERB (DST-SERB)
  2. Department of Biotechnology (DBT)

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This study demonstrates that all trans retinoic acid can alleviate inflammatory symptoms in benzo(a)pyrene-induced mice, reduce COX-2 gene expression, and prevent carcinogenesis.
Aim: Inflammation provides favourable microenvironment for cancer development. An enhanced COX-2 gene expression is a key inflammatory mediator of cancers and the drug that inhibits it, helps to manage cancer effectively and increases survival rate. The objective is to analyse the inflammatory changes and COX-2 gene expression in benzo (a) pyrene induced mice and to evaluate the regulatory effect of all trans retinoic acid. Materials and methods: The body and organ weights were recorded in B(a)P induced mice. The haematological parameters and serum inflammatory markers of carcinogenesis were tested. The H & E stained liver and lung tissues were examined for histopathologic changes. The COX-2 gene expression was analysed by RT-PCR and qPCR in lung and liver. Key findings: The decreased body weight, increased organ weights and the damages in liver and lung were observed in B(a)P induced mice and were prevented significantly upon ATRA treatment. The lowered Hb, RBC and lymphocytes and an enhanced WBC, monocytes and neutrophils observed in B(a)P group were significantly reversed in treated group. A drastic increase in cancer associated inflammatory markers observed in B(a)P induced mice were significantly (P <= 0.001) reduced in treated mice. The RT-PCR product density of COX-2 gene was very high in B(a)P group (lung-0.43 +/- 0.06; liver-0.39 +/- 0.04) significantly lower in treated group (lung-0.12 +/- 0.03; liver-0.08 +/- 0.03) with a significant difference in RQ values (B(a)P lung-18.46 +/- 0.04, liver-12.46 +/- 0.08; treated lung-5.93 +/- 0.07, liver-2.92 +/- 0.10). Significance: The ATRA has decreased the inflammatory condition with downregulation of COX-2 gene expression and thereby prevented carcinogenesis during early stage of B(a)P induced cancer development.

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