International Immunopharmacology ( IF 4.8 ) Pub Date : 2021-11-19 , DOI: 10.1016/j.intimp.2021.108285 Tissiane Eid Barbosa Ashino 1 , Monielle Leal Sant Ana 2 , Ariane Harumi Yoshikawa 3 , Lucas Possebon 1 , Sara de Souza Costa 1 , Melina Mizusaki Iyomasa-Pilon 4 , Helena Ribeiro Souza 1 , Giovana Aparecida Gonçalves 5 , Sonia Maria Oliani 6 , Ana Paula Girol 7
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.
中文翻译:
Piperlongumin在预防因苯并芘致癌物暴露于肺部引起的炎症损伤中的保护作用
苯并芘是具有致癌能力的主要多环芳烃之一。研究表明,消炎药可以降低肺癌的发病率。在这种情况下,我们重点介绍 Piperlongumin (PL),一种来自 Piper longum 的生物碱,具有抗炎特性。因此,我们的目的是研究 PL 在 Balb/c 小鼠中苯并芘诱导的肺癌发生模型中的作用。将动物分为 3 组(n = 10/组):假手术(10% DMSO)、苯并芘(100 mg/kg,在 DMSO 中稀释)诱导 12 周(BaP)和苯并芘诱导并用 PL 处理(BaP/PL) (2 mg/kg in 10% DMSO) 从诱导后第 8 周开始。每天对动物称重并在第 12 周进行体积描记术。分析血液中的基因毒性和血红蛋白水平并定量支气管肺泡灌洗液 (BAL) 中的白细胞。收集肺用于组织病理学评估、膜联蛋白 A1 (AnxA1)、环氧合酶 2 (COX-2)、抗凋亡蛋白 Bcl-2 和核转录因子 (NF-kB) 的免疫组织化学研究以及白细胞介素细胞因子 (IL) 的测量-1β、IL-17 和肿瘤坏死因子 (TNF) -α。PL 治疗降低了频率、容量和肺通气的肺参数 (p < 0,001),减少了 BAL 中的淋巴细胞、单核细胞和中性粒细胞 (p < 0,05) 以及血红蛋白水平 (p < 0,01)。与 BaP 组相比,PL 给药还减少了 DNA 损伤并保留了肺部结构。而且,PL 的抗炎作用通过维持 AnxA1 水平、降低 COX-2 (p < 0,05)、Bcl-2 (p < 0,01) 和 NF-kB (p < 0,001) 表达和降低 IL-1β、IL-17 (p < 0,01) 和 TNF-α (p < 0,05) 水平。结果显示了 PL 在治疗肺部抗炎和抗肿瘤疾病方面的治疗潜力,具有良好的治疗意义。