Abdelzaher Walaa Yehia, Nassan Mohamed A, Ahmed Sabreen Mahmoud, Welson Nermeen N, El-Saber Batiha Gaber, Khalaf Hanaa Mohamed
Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61519, Egypt.
Department of Clinical Laboratory Sciences, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Feb 16;15(2):232. doi: 10.3390/ph15020232.
The current research aimed to examine the ameliorative role of febuxostat (FEB), a highly potent xanthine oxidase inhibitor, against 5-fluorouracil (5-FU)-induced parotid salivary gland damage in rats, as FEB is a pleiotropic drug that has multiple pharmacological effects. A total of 32 Wistar adult male rats were randomly arranged into four groups. Group 1: the control group; given only the vehicle for 14 days, then given a saline i.p. injection from the 10th to the 14th day. Group 2: the FEB group; rats received FEB (10 mg/kg) once daily po for 14 days before receiving a saline i.p. injection from the 10th to the 14th day. Group 3: the 5-FU group; from the 10th to the 14th day, rats received an intraperitoneal injection of 5-FU (35 mg/kg/day). Group 4: the FEB/5-FU group; rats were pre-treated with FEB po for 14 days before receiving 5-FU i.p injections for five consecutive days from the 10th to the 14th day. Parotid gland damage was detected histologically and biochemically by the evaluation of oxidative stress markers (malondialdehyde (MDA) and nitric oxide levels (NOx)), oxidant defences (reduced glutathione (GSH) and superoxide dismutase (SOD)), inflammatory markers (tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β)), and transient receptor potential canonical1 (TRCP1) and C/EBP homologous protein (CHOP). FEB pre-treatment reduced MDA, TNF-, and IL-1 while increasing SOD, GSH, and NOx. FEB also significantly increased TRPC1 and decreased CHOP in parotid gland tissue. In conclusion, FEB pre-treatment reduced 5-FU-induced parotid salivary gland damage not only through its powerful anti-inflammatory and antioxidant effects, but also through its effect on the TRPC1/CHOP signalling pathway.
目前的研究旨在探讨非布司他（FEB），一种高效的黄嘌呤氧化酶抑制剂，对5-氟尿嘧啶（5-FU）诱导的大鼠腮腺唾液腺损伤的改善作用，因为FEB是一种具有多种药理作用的多效性药物。总共32只成年雄性Wistar大鼠被随机分为四组。第1组：对照组；仅给予赋形剂14天，然后从第10天至第14天腹腔注射生理盐水。第2组：FEB组；大鼠在第10天至第14天腹腔注射生理盐水前，每天口服一次FEB（10mg/kg），共14天。第3组：5-FU组；从第10天至第14天，大鼠腹腔注射5-FU（35mg/kg/天）。第4组：FEB/5-FU组；大鼠在第10天至第14天连续5天腹腔注射5-FU前，口服FEB预处理14天。通过评估氧化应激标志物（丙二醛（MDA）和一氧化氮水平（NOx））、抗氧化防御（还原型谷胱甘肽（GSH）和超氧化物歧化酶（SOD））、炎症标志物（肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β））以及瞬时受体电位香草酸亚型1（TRPC1）和C/EBP同源蛋白（CHOP），从组织学和生化方面检测腮腺损伤。FEB预处理降低了MDA、TNF-和IL-1水平，同时提高了SOD、GSH和NOx水平。FEB还显著增加了腮腺组织中的TRPC1水平并降低了CHOP水平。总之，FEB预处理不仅通过其强大的抗炎和抗氧化作用，还通过其对TRPC1/CHOP信号通路的影响，减轻了5-FU诱导的腮腺唾液腺损伤。
