Faculty of Veterinary Medicine, Department of Pathology, Kastamonu University, 37150, Kastamonu, Turkey.
Faculty of Dentistry, Department of Basic Science, Istanbul Gelişim University, 34295, Istanbul, Turkey.
BMC Complement Med Ther. 2022 Dec 13;22(1):331. doi: 10.1186/s12906-022-03803-x.
Tacrolimus (FK506) is an immunosuppressive agent and has toxic side effects such as nephrotoxicity, hepatotoxicity, and neurotoxicity. In our study, we aimed to investigate the protective effect of silymarin on renal and hepatic toxicity considered to be tacrolimus related.
In this 6-week experimental study, 46 eight-week-old healthy male rats were used. The groups comprised the Control (healthy rats, n = 6), Tac (tacrolimus 1 mg/kg, n = 8), silymarin 100 mg/kg (SLI 100 mg/kg n = 8), Tac + SLI 100 (tacrolimus 1 mg/kg + SLI 100 n = 8), SLI 200 (SLI 200 mg/kg n = 8), and Tac + SLI 200 (tacrolimus 1 mg/kg + SLI 200 mg/kg n = 8). After 6 weeks, all rats were sacrificed, and the tissue follow-up procedure was performed for kidney and liver tissues, histopathology, and in situ TUNEL analysis. Blood samples were analyzed for the total antioxidant capacity (TAC), total oxidant capacity (TOC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), albumin, total bilirubin, creatine.
Histopathological findings of kidney and liver tissue of rats were determined to increase statistically in Tac group compared to SLI 1 00 and SLI 200 groups (P < 0.05). In addition, the Tac + SLI 100 and Tac + SLI 200 groups were found to be statistically similar to the Control group (P > 0.05). The in situ TUNEL method showed that the tacrolimus increased apoptosis while the silymarin decreased it. TOC levels increased statistically in Tac groups compared to silymarin-treated groups (P < 0.05). Although the TAC level was not statistically significant among the experimental groups (P > 0.05), the lowest was measured in the Tac group. The ALT, AST, GGT, total bilirubin, and creatine values were higher in the Tac group than in the silymarin groups (P < 0.05). There was no statistically significant difference between the groups with regard to the albumin level (P > 0.05).
In our study, we determined that tacrolimus caused damage to kidney and liver tissue. Histopathological, biochemical and apoptotic findings show that silymarin has a protective effect against nephrotoxicity and hepatotoxicity caused by tacrolimus.
他克莫司（FK506）是一种免疫抑制剂，具有肾毒性、肝毒性和神经毒性等毒副作用。在我们的研究中，我们旨在研究水飞蓟素对被认为与他克莫司相关的肾毒性和肝毒性的保护作用。
在这项为期 6 周的实验研究中，使用了 46 只 8 周龄的健康雄性大鼠。这些组包括对照组（健康大鼠，n=6）、Tac（他克莫司 1mg/kg，n=8）、水飞蓟素 100mg/kg（SLI 100mg/kg，n=8）、Tac+SLI 100（他克莫司 1mg/kg+水飞蓟素 100mg/kg，n=8）、水飞蓟素 200mg/kg（SLI 200mg/kg，n=8）和 Tac+SLI 200（他克莫司 1mg/kg+水飞蓟素 200mg/kg，n=8）。6 周后，所有大鼠均被处死，并对肾脏和肝脏组织进行组织学随访、组织病理学检查和原位 TUNEL 分析。对血液样本进行总抗氧化能力（TAC）、总氧化能力（TOC）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、γ-谷氨酰转移酶（GGT）、白蛋白、总胆红素、肌酸的分析。
与 SLI 100 和 SLI 200 组相比，Tac 组大鼠的肾脏和肝脏组织的组织病理学发现明显增加（P<0.05）。此外，Tac+SLI 100 和 Tac+SLI 200 组与对照组相比无统计学差异（P>0.05）。原位 TUNEL 法显示，他克莫司增加了细胞凋亡，而水飞蓟素则减少了细胞凋亡。与水飞蓟素治疗组相比，Tac 组的 TOC 水平明显升高（P<0.05）。虽然实验组之间的 TAC 水平没有统计学意义（P>0.05），但 Tac 组的 TAC 水平最低。与水飞蓟素组相比，Tac 组的 ALT、AST、GGT、总胆红素和肌酸水平较高（P<0.05）。各组白蛋白水平无统计学差异（P>0.05）。
在我们的研究中，我们确定他克莫司导致了肾脏和肝脏组织的损伤。组织病理学、生化和细胞凋亡发现表明，水飞蓟素对他克莫司引起的肾毒性和肝毒性具有保护作用。
