Department of Biochemistry, Faculty of Science, King Abdulaziz University, P.O. Box: 80200, Zip Code: 21589, Jeddah, Kingdom of Saudi Arabia.
Daru. 2019 Jun;27(1):525-531. doi: 10.1007/s40199-019-00252-9. Epub 2019 Mar 22.
The major adverse effect associated with systemic administration of Fluconazole (FLZ), is hepatic toxicity. FLZ is most commonly used antifungal drug in treatment of invasive fungal infections.
FLZ toxicity was challenged by individual and in combination of three vitamins (B1, B2 B3). Animals were divided nine groups with six animals in each group. FLZ, at a dose of 50 mg/kg b.w, was orally administered for 90 days in experimental animals. Vitamins as individual or in combination was administered concomitantly to challenge or alleviate the toxicity of FLZ. They were sacrificed at the end of protocol for biochemical and histopathology analysis. Focus was made to observe the role of these micro nutrient's (vitamins) on liver for alteration in of pathological and physiological effects by FLZ in the Wistar albino rats.
Combination of vitamin B1 + B2 + B3 in FLZ induced toxicity was able to restore the level of alkaline phosphatase (ALP) near to normal but with high level of ALP in B1 Control group. Aspartate aminotransferase (AST) was restored to normal in FLZ + B1, FLZ + B2 and FLZ + B1 + B2 + B3 groups and vice versa in FLZ + B3 group animals. Further the level of alanine aminotransferase (ALT) was restored to normal in FLZ + B3 animals. There were no significant changes found in total bilirubin (TBI), and direct bilirubin (DBI) as compare to normal control. Histopathological studies on animals' studies validated the serological results in normalizing the cellular architecture of liver.
Restoration of altered biochemical parameters and cellular architecture of hepatocytes by different combination of these vitamins proves the chemo preventive potential of these micro nutrients' in FLZ toxicity. Graphical abstract Vitamin B combination attenuates fluconazole toxicity.
氟康唑（FLZ）全身给药的主要不良反应是肝毒性。FLZ 是治疗侵袭性真菌感染最常用的抗真菌药物。
通过单独和三种维生素（B1、B2、B3）组合来挑战 FLZ 毒性。将动物分为 9 组，每组 6 只。实验动物口服给予 FLZ ，剂量为 50mg/kg b.w，共 90 天。维生素单独或联合给药，以挑战或减轻 FLZ 的毒性。在方案结束时处死动物，进行生化和组织病理学分析。重点观察这些微量营养素（维生素）对肝脏的作用，观察 FLZ 在 Wistar 白化大鼠中对病理和生理效应的改变。
FLZ 诱导毒性中维生素 B1+B2+B3 的联合用药能够使碱性磷酸酶（ALP）水平接近正常，但 B1 对照组的 ALP 水平较高。天冬氨酸氨基转移酶（AST）在 FLZ+B1、FLZ+B2 和 FLZ+B1+B2+B3 组恢复正常，而在 FLZ+B3 组动物中则相反。此外，FLZ+B3 组动物的丙氨酸氨基转移酶（ALT）水平恢复正常。与正常对照组相比，总胆红素（TBI）和直接胆红素（DBI）没有显著变化。动物研究的组织病理学研究证实了血清学结果在使肝细胞的细胞结构正常化方面的作用。
不同维生素组合对生化参数和肝细胞细胞结构的改变的恢复证明了这些微量营养素在 FLZ 毒性中的化学预防潜力。
图表摘要 维生素 B 组合减轻氟康唑毒性。
