Mandal Santa, Verma Navneet, Bora Nilutpal S, Dey Piyali, Islam Johirul, Dwivedi Sanjai K, Chattopadhyay Pronobesh
Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, Assam, India.
School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, India.
Inhal Toxicol. 2020 Jun;32(7):299-310. doi: 10.1080/08958378.2020.1784321. Epub 2020 Jun 28.
To explore the therapeutic role of a single dose combination of montelukast (MON) and dexamethasone (DXM) through intra-peritoneal route against paraquat (PQ)-intoxicated experimental Wistar rats.
the survival rate was investigated following the administration of both MON and DXM in PQ exposed rats. Lungs parameters including enhanced pause (Penh), tidal volume (TV) and breath per minute (BPM) were determined using the whole body plethysmograph (WBP). Further chest imaging and histopathological studies were conducted to evaluate the lungs injury. the antioxidant activity was carried out by determining the levels of catalase (SOD), superoxide dismutase (CAT) and glutathione peroxidase (GSH-Px). Lungs tissue concentration of different proinflammatory cytokines like IL-1β, IL-6, TGF-β1 and TNF-α was also determined. Finally, expression of NF-kB and p-NF-kB was investigated by western blot.
Results of survival rate and levels of lungs parameters indicated therapeutic potential of combination treatment of MON and DXM. Protective activity on lungs was reflected in chest imaging and histopathological investigations. Moreover, combination treatment exhibited significant increased levels of all anti-oxidant parameters. Significant decrease in the levels of IL-1β; IL-6; TGF-β1 and TNF-α was also observed with the combination treatment of MON and DXM. Evidence of significant down regulation of NF-kB and phospho-NF-kB was also found with the combination treatment of MON and DXM.
Given the advantage of therapeutic synergism activity of MON and DXM, it may be used in the prophylaxis of PQ-intoxication following clinical trials.
探讨腹腔注射孟鲁司特（MON）和地塞米松（DXM）单剂量联合用药对百草枯（PQ）中毒的实验性Wistar大鼠的治疗作用。
在暴露于PQ的大鼠中给予MON和DXM后，研究其存活率。使用全身体积描记器（WBP）测定包括增强暂停（Penh）、潮气量（TV）和每分钟呼吸次数（BPM）在内的肺参数。进一步进行胸部成像和组织病理学研究以评估肺损伤。通过测定过氧化氢酶（SOD）、超氧化物歧化酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的水平来进行抗氧化活性检测。还测定了肺组织中不同促炎细胞因子如IL-1β、IL-6、TGF-β1和TNF-α的浓度。最后，通过蛋白质印迹法研究NF-kB和p-NF-kB的表达。
存活率和肺参数水平的结果表明MON和DXM联合治疗具有治疗潜力。胸部成像和组织病理学研究反映了对肺的保护作用。此外，联合治疗显示所有抗氧化参数水平显著升高。MON和DXM联合治疗还观察到IL-1β、IL-6、TGF-β1和TNF-α水平显著降低。MON和DXM联合治疗还发现NF-kB和磷酸化NF-kB显著下调的证据。
鉴于MON和DXM具有治疗协同活性的优势，经临床试验后，它可能用于预防PQ中毒。
