Protective effects of piperlongumin in the prevention of inflammatory damage caused by pulmonary exposure to benzopyrene carcinogen

[Display omitted] •Important anti-inflammatory effects of PL in lungs of benzopyrene-induced animals.•Pulmonary parameters and blood hemoglobin levels were normalized by PL.•PL decreased DNA damage, inflammatory influx and disarrangement of lung structure.•PL reduced COX-2, Bcl-2 and NF-kB expressio...

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Published in:	International immunopharmacology Vol. 101; no. Pt B; p. 108285
Main Authors:	Ashino, Tissiane Eid Barbosa, Sant́ Ana, Monielle Leal, Yoshikawa, Ariane Harumi, Possebon, Lucas, de Souza Costa, Sara, Iyomasa-Pilon, Melina Mizusaki, Souza, Helena Ribeiro, Gonçalves, Giovana Aparecida, Oliani, Sonia Maria, Girol, Ana Paula
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-12-2021 Elsevier BV
Subjects:	Animals Annexin A1 - metabolism Anti-inflammatory agents Anti-Inflammatory Agents - pharmacology AnxA1 Apoptosis Bcl-2 protein Benzo(a)pyrene - metabolism Benzopyrene Benzopyrenes Blood Bronchoalveolar Lavage Fluid Bronchus Carcinogenesis Carcinogens Carcinogens - metabolism Cyclooxygenase 2 - metabolism Cyclooxygenase-2 Cytokines Cytokines - metabolism Damage prevention DNA damage Genotoxicity Hemoglobin IL-1β Inflammation - metabolism Interleukin 17 Interleukin-1beta Leukocytes Leukocytes (neutrophilic) Lung - pathology Lung cancer Lung diseases Lymphocytes Male Mice Mice, Inbred BALB C Monocytes Natural bioactive compound Neutrophils - metabolism NF-kappa B - metabolism NF-κB protein Polycyclic aromatic hydrocarbons Smoking Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-TNF Tumor necrosis factor-α MCP-1 COX-2 DMSO Lung cancer GSTP1 Sham NF-kB NaOH TGF- α ATII NBC BaP HIF-α ANOVA HUVEC AnxA1 PBS CBR1 SCLC Cytokines DAB NSCLC ip EDTA IL-1β MAPK Natural bioactive compound BAL IL-6 TNF-α UNIFIPA DNA PAH µL IL-17 ROS Bax NaCl PL HE Hep-2 Smoking
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Summary:	[Display omitted] •Important anti-inflammatory effects of PL in lungs of benzopyrene-induced animals.•Pulmonary parameters and blood hemoglobin levels were normalized by PL.•PL decreased DNA damage, inflammatory influx and disarrangement of lung structure.•PL reduced COX-2, Bcl-2 and NF-kB expressions but maintained high levels of AnxA1.•IL-1β, IL-17 and TNF-α levels were decreased by PL in benzopyrene-induced animals. Benzopyrene is one of the main polycyclic aromatic hydrocarbons with carcinogenic capacity. Research has shown that anti-inflammatory drugs can reduce the incidence of lung cancer. In this scenario, we highlight piperlongumin (PL), an alkaloid from Piper longum with anti-inflammatory properties. Therefore, our aim was to study the effect of PL administration in a model of pulmonary carcinogenesis induced by benzopyrene in Balb/c mice. Animals were divided into 3 groups (n = 10/group): sham (10% DMSO), induced by benzopyrene (100 mg/kg, diluted in DMSO) without treatment (BaP) for 12 weeks and induced by benzopyrene and treated with PL (BaP/PL) (2 mg/kg in 10% DMSO) from the eighth week post-induction. Animals were weighed daily and pletsmography was performed in the 12th week. Genotoxicity and hemoglobin levels were analyzed in blood and quantification of leukocytes in bronchoalveolar lavage (BAL). Lungs were collected for histopathological evaluation, immunohistochemical studies of annexin A1 (AnxA1), cyclooxygenase 2 (COX-2), anti-apoptotic protein Bcl-2 and nuclear transcription factor (NF-kB) and also the measurement of interleukin cytokines (IL)-1β, IL-17 and tumor necrosis factor (TNF) -α. Treatment with PL reduced the pulmonary parameters (p < 0,001) of frequency, volume and pulmonary ventilation, decreased lymphocytes, monocytes and neutrophils in BAL (p < 0,05) as well as blood hemoglobin levels (p < 0,01). PL administration also reduced DNA damage and preserved the pulmonary architecture compared to the BaP group. Moreover, the anti-inflammatory effect of PL was evidenced by the maintenance of AnxA1 levels, reduction of COX-2 (p < 0,05), Bcl-2 (p < 0,01) and NF-kB (p < 0,001) expressions and decreased IL-1β, IL-17 (p < 0,01) and TNF-α (p < 0,05) levels. The results show the therapeutic potential of PL in the treatment of pulmonary anti-inflammatory and anti-tumor diseases with promising therapeutic implications.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1567-5769 1878-1705
DOI:	10.1016/j.intimp.2021.108285