Department of Biochemistry, National Organization for Drug Control and Research (NODCAR)/Egyptian Drug Authority (EDA), Cairo, Egypt.
Department of Biotechnology &Molecular drug evaluation, National Organization for Drug Control and Research (NODCAR)/Egyptian Drug Authority (EDA), Cairo, Egypt.
BMC Complement Med Ther. 2024 Apr 5;24(1):153. doi: 10.1186/s12906-024-04447-9.
Vortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.
The experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.
Interestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.
Thus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.
沃替西汀（VORTX）是一种强效和选择性的选择性 5-羟色胺再摄取抑制剂（SSRI），主要用于治疗抑郁症和情绪障碍等疾病，是首选药物之一。有限的先前研究结果表明，沃替西汀每日治疗与肝损伤和肝毒性有关。芦丁（RUT）具有抗氧化特性，已证明具有多种有益的健康作用，包括肝保护作用。因此，本研究旨在评估和评估 RUT 对每日低剂量和高剂量 VORTX 给药的肝毒性作用的改善作用。
实验设计包括 6 组大鼠，每组均分为两组。对照组、RUT（25mg/kg）暴露组、VORTX（28mg/kg）暴露组、VORTX（28mg/kg）+RUT（25mg/kg）暴露组、VORTX（80mg/kg）暴露组和 VORTX（80mg/kg）+RUT（25mg/kg）暴露组。经过 30 天的每日暴露期后，对血清肝酶活性、肝毒性生物标志物、肝抗氧化内源性酶、DNA 片段化和肝组织组织病理学研究进行评估。
有趣的是，RUT 的每日联合给药减轻了与 VORTX 相关的肝损伤和肝毒性的风险。所有检测到的肝功能、氧化应激和炎症生物标志物（包括天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、乳酸脱氢酶（LDH）、白蛋白、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、谷胱甘肽 S-转移酶（GST）、总蛋白、酸性磷酸酶、N-乙酰基/-β-葡萄糖苷酶（β-NAG）、β-半乳糖苷酶（β-Gal）、甲胎蛋白（AFP）、半胱天冬酶 3 和细胞色素 C 以及组织病理学研究都有显著改善，与对照组和单独 RUT 组相比。
因此，RUT 可被认为是一种潜在的有效互补治疗方法，可预防每日或长期给予 VORTX 引起的肝毒性和肝损伤。
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