Department of Pharmacology & Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Department of Biochemistry, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt.
Drug Chem Toxicol. 2024 Nov;47(6):897-908. doi: 10.1080/01480545.2024.2310641. Epub 2024 Mar 4.
Depression is a persistent illness affecting health, behavior, and performance in life. Worldwide morbidity and mortality are caused by depression. The current study intended to explore fumaric acid's potential protective effect against ciprofloxacin-provoked depression in rats and to determine its mechanism of action by studying its antioxidant and anti-inflammatory properties. Five groups of male Wistar albino rats (120 g ± 20) were employed; the first group received physiological saline, the second group received fumaric acid (80 mg/kg/day; orally) for 3 weeks, the third group was administered ciprofloxacin (50 mg/kg/day; orally) for 3 weeks to induce depression, the fourth group received a daily low dose of fumaric acid (40 mg/kg; orally) concurrent with ciprofloxacin and the fifth group received a daily high dose of fumaric acid (80 mg/kg; orally) concurrent with ciprofloxacin for 21 days. Then, behavior tests, oxidative stress indicators, inflammatory biomarkers, neurotransmitters, p190 Rho GTP, and histopathological examination were evaluated. Ciprofloxacin significantly increased oxidative stress biomarkers [malondialdehyde (MDA) as a lipid peroxidation marker and nitric oxide (NO)] and biomarkers of inflammation (TLR-4)] and tumor necrosis factor-alpha (TNF-α) with reduction in the activities of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and catalase as well as brain contents of neurotransmitters and P190-RHO GTP. In addition, it causes necrosis of neurons and mild loss of Purkinje cells. Fumaric acid eliminates these effects of ciprofloxacin. Fumaric acid has beneficial effects as an anti-depressant in Wistar albino male rats that received ciprofloxacin.
抑郁症是一种影响健康、行为和生活表现的慢性疾病。全球的发病率和死亡率都是由抑郁症引起的。本研究旨在探讨富马酸对环丙沙星诱发的大鼠抑郁的潜在保护作用，并通过研究其抗氧化和抗炎特性来确定其作用机制。本研究采用了五组雄性 Wistar 白化大鼠（120g±20）：第一组给予生理盐水，第二组给予富马酸（80mg/kg/天；口服）3 周，第三组给予环丙沙星（50mg/kg/天；口服）3 周以诱发抑郁，第四组给予低剂量富马酸（40mg/kg/天；口服）与环丙沙星同时给药，第五组给予高剂量富马酸（80mg/kg/天；口服）与环丙沙星同时给药 21 天。然后，评估了行为测试、氧化应激指标、炎症生物标志物、神经递质、p190 Rho GTP 和组织病理学检查。环丙沙星显著增加了氧化应激生物标志物[丙二醛（MDA）作为脂质过氧化标志物和一氧化氮（NO）]和炎症生物标志物（TLR-4）和肿瘤坏死因子-α（TNF-α），同时降低了核因子红细胞 2 相关因子 2（Nrf-2）和过氧化氢酶的活性以及神经递质和 P190-RHO GTP 的脑含量。此外，它还导致神经元坏死和浦肯野细胞轻度丢失。富马酸消除了环丙沙星的这些作用。富马酸对接受环丙沙星的雄性 Wistar 白化大鼠具有抗抑郁作用。
