Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), 68820Al-Azhar University, Cairo, Egypt.
Hum Exp Toxicol. 2021 Dec;40(12_suppl):S509-S518. doi: 10.1177/09603271211051597. Epub 2021 Oct 20.
Fluoxetine (FLX) has been widely used as first-line treatment in cases of depression and other neuropsychiatric disorders. Although its safety has been approved, the use of FLX was associated with liver injury and chronic liver disease. Vinpocetine (Vinpo), a nootropic drug, possesses antioxidant and anti-inflammatory effects.
This study aimed to evaluate the protective effects of Vinpo on FLX-induced liver damage pointing to the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and nuclear factor erythroid 2-related factor 2 (Nrf2).
Rats were randomized to four groups: control group, Vinpo group (20 mg/kg/day; orally), FLX group (10 mg/kg/day; orally), and Vinpo + FLX group.
FLX-induced liver damage was evidenced through elevated liver function biomarkers and induced hepatic histopathological changes. Concurrent Vinpo treatment resulted in a significant decrease in hepatotoxicity biomarkers and histopathological alterations. FLX-induced oxidative stress and inflammation were attenuated by Vinpo. In addition, Vinpo attenuated the hepatic NRF2 and HO-1 levels and up-regulated PPAR-γ expression. Moreover, FLX elevated Bcl-2-associated X protein (Bax) mRNA expression and decreased B-cell lymphoma 2 (Bcl2) mRNA expression were markedly reversed by Vinpo.
Vinpo possesses ameliorative effects against FLX-induced liver injury in rats. This effect may be due to attenuation of oxidative stress and inflammation, in addition to upregulation of PPAR-γ expression.
氟西汀（FLX）已被广泛用作抑郁症和其他神经精神疾病的一线治疗药物。尽管其安全性已得到认可，但 FLX 的使用与肝损伤和慢性肝病有关。长春西汀（Vinpo）是一种益智药，具有抗氧化和抗炎作用。
本研究旨在评估长春西汀对 FLX 诱导的肝损伤的保护作用，指出过氧化物酶体增殖物激活受体-γ（PPAR-γ）和核因子红细胞 2 相关因子 2（Nrf2）的作用。
将大鼠随机分为四组：对照组、长春西汀组（20mg/kg/天；口服）、FLX 组（10mg/kg/天；口服）和长春西汀+FLX 组。
FLX 诱导的肝损伤表现为肝功能生物标志物升高和肝组织病理学改变。同时给予长春西汀治疗可显著降低肝毒性生物标志物和组织病理学改变。长春西汀减轻了 FLX 诱导的氧化应激和炎症。此外，长春西汀还降低了 NRF2 和 HO-1 水平，并上调了 PPAR-γ 的表达。此外，FLX 升高了 B 细胞淋巴瘤 2 相关 X 蛋白（Bax）mRNA 表达，降低了 B 细胞淋巴瘤 2（Bcl2）mRNA 表达，长春西汀明显逆转了这一现象。
长春西汀对大鼠 FLX 诱导的肝损伤具有改善作用。这种作用可能是由于抑制了氧化应激和炎症，同时上调了 PPAR-γ 的表达。
