Clinical Pharmacy Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527, Tanta, Egypt.
Clinical Pharmacy Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
Int Immunopharmacol. 2021 Apr;93:107372. doi: 10.1016/j.intimp.2021.107372. Epub 2021 Jan 29.
Chronic pancreatitis is considered a common gastrointestinal disorder, with significant morbidity and mortality. Fluoride is an important agent for the development of our body systems, especially for bone and teeth, however on its excess consumption, it deposits in different body tissues, especially the pancreas, causing its chronic inflammation and destruction. Fraxetin proved to possess versatile activities including; antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic activities. In the present study, we have evaluated the fraxetin potentiality to prevent fluoride-induced chronic pancreatitis in rats, by evaluating animal body weights and body weight gain rate, serum amylase, and lipase activities, pancreatic oxidative stress markers, cytokines, apoptotic markers, myeloperoxidase, and hydroxyproline levels, and histopathological changes. Nine-weeks-old male Wistar rats drank distilled water containing 500 ppm sodium fluoride (NaF) for 60 days to induce chronic pancreatitis. Oral fraxetin (20, 40, and 80 mg/kg/day) received simultaneously to prevent chronic pancreatitis development. Fraxetin in a dose-dependent manner alleviated chronic pancreatitis induced by NaF, as it restored the decreased body weight and weight gain rate, decreased the elevated serum amylase and lipase activities, pancreatic IL-6, TNF-α, MDA, caspase-3, MPO and hydroxyproline levels, and Bax/Bcl-2 ratio, enhanced pancreatic CAT and SOD activities, and GSH levels, besides it augmented the elevated IL-10 level, with the restoration of normal pancreatic architecture. Therefore, fraxetin could be a promising agent recommended for the prevention of fluoride-induced chronic pancreatitis in endemic areas.
慢性胰腺炎被认为是一种常见的胃肠道疾病，具有较高的发病率和死亡率。氟化物是我们身体系统发育的重要物质，特别是对骨骼和牙齿。然而，过量摄入氟化物会导致其在不同的身体组织中沉积，特别是在胰腺中，引起慢性炎症和破坏。瑞香素已被证明具有多种活性，包括抗氧化、抗炎、抗纤维化和抗细胞凋亡作用。在本研究中，我们评估了瑞香素预防氟诱导的大鼠慢性胰腺炎的潜力，通过评估动物体重和体重增长率、血清淀粉酶和脂肪酶活性、胰腺氧化应激标志物、细胞因子、凋亡标志物、髓过氧化物酶和羟脯氨酸水平以及组织病理学变化。9 周龄雄性 Wistar 大鼠饮用含 500ppm 氟化钠（NaF）的蒸馏水 60 天，以诱导慢性胰腺炎。同时给予瑞香素（20、40 和 80mg/kg/天）口服，以预防慢性胰腺炎的发生。瑞香素以剂量依赖的方式缓解了由 NaF 诱导的慢性胰腺炎，因为它恢复了降低的体重和体重增长率，降低了升高的血清淀粉酶和脂肪酶活性、胰腺白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）、髓过氧化物酶（MPO）和羟脯氨酸水平，以及 Bax/Bcl-2 比值，增强了胰腺过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性以及谷胱甘肽（GSH）水平，同时还增加了升高的白细胞介素-10（IL-10）水平，并恢复了正常的胰腺结构。因此，瑞香素可能是一种有前途的药物，推荐用于预防氟诱导的地方性慢性胰腺炎。
