Laboratory of Animal and Human Physiology, Department of Zoology (Animal Sciences), Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Laboratory of Animal and Human Physiology, Department of Zoology (Animal Sciences), Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Toxicol Appl Pharmacol. 2022 Oct 1;452:116192. doi: 10.1016/j.taap.2022.116192. Epub 2022 Aug 8.
Use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of gastric ulcers. Excellent therapeutic properties have made the use of NSAIDs widespread. Nano-drug delivery to reduce systemic toxicity through modulating drug pharmacokinetics may be a better choice. Presently, we investigated if naproxen nanoformulation (PVA capped NPRS-MgO NPs) is less toxic to be used as an alternative drug. Groups of mice were assigned to control, NPRS-treated, CNF-treated, UNF-treated, and MgO NPs-treated groups. Analyses included gross examination of gastric mucosa, calculation of ulcer and inhibition indices, determination of tissue levels of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and reduced glutathione (GSH), histological and immunohistochemical assessment of i-NOS, COX-2, and caspase-3 of stomach mucosa, q-PCR for the detection of mRNA expression of IL-1β, IL-6, and TNF-α. Results were compared statistically at P < 0.05. Compared to NPRS-treated mice which developed multiple ulcers, had elevated MDA and ROS levels, and deceased CAT, POD, SOD, and GSH levels, significantly increased expression of IL-1β, IL-6, and TNF-α mRNA, damaged surface epithelium with disrupted glandular architecture and leucocyte infiltration of lamina propria with a marked increase in mucosal COX-2, i-NOS, and caspase-3 expression, oral administration of coated and uncoated naproxen nanoformulations prevented the gross mucosal damage by a restoration of all biochemical, histological, and immunohistochemical alterations to near control levels. The present study demonstrates that naproxen sodium nanoformulation has a gastroprotective action and in the clinical setting can be a better alternative to conventional naproxen.
非甾体抗炎药(NSAIDs)的使用是导致胃溃疡的主要原因之一。由于其出色的治疗效果,NSAIDs 的应用非常广泛。通过调节药物药代动力学来实现纳米药物递送,以降低全身毒性,可能是一个更好的选择。目前,我们研究了萘普生纳米制剂(PVA 封端的 NPRS-MgO NPs)是否毒性更低,可作为替代药物。将小鼠分为对照组、NPRS 处理组、CNF 处理组、UNF 处理组和 MgO NPs 处理组。分析包括胃黏膜大体检查、溃疡和抑制指数计算、组织内活性氧(ROS)、丙二醛(MDA)、过氧化氢酶(CAT)、过氧化物酶(POD)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)水平测定、胃黏膜 i-NOS、COX-2 和 caspase-3 的组织学和免疫组织化学评估、IL-1β、IL-6 和 TNF-α 的 mRNA 表达的 q-PCR 检测。结果在 P < 0.05 时进行统计学比较。与 NPRS 处理组相比,NPRS 处理组小鼠出现多发性溃疡,MDA 和 ROS 水平升高,CAT、POD、SOD 和 GSH 水平降低,IL-1β、IL-6 和 TNF-α mRNA 表达显著增加,表面上皮受损,腺体结构紊乱,固有层白细胞浸润,黏膜 COX-2、i-NOS 和 caspase-3 表达明显增加,口服涂层和未涂层的萘普生纳米制剂可防止大体黏膜损伤,使所有生化、组织学和免疫组织化学改变恢复到接近对照水平。本研究表明,萘普生钠纳米制剂具有胃保护作用,在临床环境中可能是传统萘普生的更好替代品。