Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Toxicon. 2011 Aug;58(2):195-201. doi: 10.1016/j.toxicon.2011.05.018. Epub 2011 Jun 7.
Cyanobacterial blooms that generate microcystins (MCYSTs) are increasingly recognized as an important health problem in aquatic ecosystems. We have previously reported the impairment of pulmonary structure and function by microcystin-LR (MCYST-LR) exposure as well as the pulmonary improvement by intraperitoneally injected (i.p.) LASSBio 596. In the present study, we aimed to evaluate the usefulness of LASSBio 596 per os on the treatment of pulmonary and hepatic injuries induced by MCYST-LR. Swiss mice received an intraperitoneal injection of 40 μl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 μg/kg). After 6 h the animals received either saline (TOX and CTRL groups) or LASSBio 596 (50 mg/kg, LASS group) by gavage. Eight hours after the first instillation, lung impedance (static elastance, elastic component of viscoelasticity and resistive, viscoelastic and total pressures) was determined by the end-inflation occlusion method. Left lung and liver were prepared for histology. In lung and hepatic homogenates MCYST-LR, TNF-α, IL-1β and IL-6 were determined by ELISA. LASSBio 596 per os (LASS mice) kept all lung mechanical parameters, polymorphonuclear (PMN) cells, pro-inflammatory mediators, and alveolar collapse similar to control mice (CTRL), whereas in TOX these findings were higher than CTRL. Likewise, liver structural deterioration (hepatocytes inflammation, necrosis and steatosis) and inflammatory process (high levels of pro-inflammatory mediators) were less evident in the LASS than TOX group. LASS and CTRL did not differ in any parameters studied. In conclusion, orally administered LASSBio 596 prevented lung and hepatic inflammation and completely blocked pulmonary functional and morphological changes induced by MCYST-LR.
蓝藻水华产生的微囊藻毒素(MCYSTs)日益被认为是水生生态系统中的一个重要健康问题。我们之前已经报道了微囊藻毒素-LR(MCYST-LR)暴露对肺结构和功能的损害,以及腹腔内注射(i.p.)LASSBio 596 对肺的改善。在本研究中,我们旨在评估口服 LASSBio 596 对 MCYST-LR 诱导的肺和肝损伤的治疗效果。瑞士小鼠接受了 40μl 生理盐水(CTRL)或亚致死剂量的 MCYST-LR(40μg/kg)的腹腔注射。6 小时后,动物分别接受生理盐水(TOX 和 CTRL 组)或 LASSBio 596(50mg/kg,LASS 组)灌胃。第一次给药后 8 小时,通过末端充气闭塞法测定肺阻抗(静态弹性、粘弹弹性的弹性成分和阻力、粘弹和总压力)。制备左肺和肝组织用于组织学检查。在肺和肝组织匀浆中,通过 ELISA 测定 MCYST-LR、TNF-α、IL-1β和 IL-6。口服 LASSBio 596(LASS 组)保持所有肺力学参数、多形核(PMN)细胞、促炎介质和肺泡塌陷与对照小鼠(CTRL)相似,而在 TOX 中这些发现高于 CTRL。同样,在 LASS 组中,肝结构恶化(肝细胞炎症、坏死和脂肪变性)和炎症过程(促炎介质水平升高)比 TOX 组更为明显。LASS 和 CTRL 在研究的任何参数上均无差异。总之,口服 LASSBio 596 可预防肺和肝炎症,并完全阻断 MCYST-LR 诱导的肺功能和形态变化。