Effect of Short-Term Tacrolimus Exposure on Rat Liver: An Insight into Serum Antioxidant Status, Liver Lipid Peroxidation, and Inflammation.
Effect of Short-Term Tacrolimus Exposure on Rat Liver: An Insight into Serum Antioxidant Status, Liver Lipid Peroxidation, and Inflammation.
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DOI：
10.1155/2021/6613786
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发表时间：
2021
影响因子：
4.6
通讯作者：
Oghumu S
中科院分区：
文献类型：
--
作者：
Fatima N;Sheikh N;Satoskar AR;Akhtar T;Tayyeb A;Ashfaq I;Ryan N;Ambreen S;Jha BK;Oghumu S
他克莫司（TAC）是一种免疫抑制药物，最适合用于肝、肾和心脏移植，以避免免疫排斥。回顾过去，大量研究报道了TAC的影响，如肾毒性、糖尿病和其他并发症。然而，关于TAC对肝脏短期暴露的信息有限。因此，本研究旨在揭示TAC短期暴露对大鼠模型的影响。分别于6、12、24、48 h时间点给药建立动物模型。采用PAS-D、网状蛋白染色、PCNA和CK-7免疫染色及肝匀浆糖原定量观察肝脏组织病理学变化。采用TUNEL法评估肝脏DNA损伤情况。测定血清中GSH浓度、SOD和CAT活性，评估抗氧化状态；测定肝组织MDA水平，作为氧化应激的生物标志物。采用RT-PCR法分析肝脏中IL-10、IL-13、SOCS-2、SOCS-3基因的表达。结果显示，所有tac治疗组的肝脏结构都发生了显著变化，表现为肝窦扩张、肝细胞紊乱、糖原沉积和网状蛋白纤维塌陷。与对照组相比，治疗组PCNA和CK-7免疫染色显著增加，tunel阳性细胞出现。TAC处理组血清抗氧化酶水平显著降低，肝脏MDA水平升高，提示氧化应激诱导。在治疗组中，细胞因子的基因表达谱显著上调，突出了炎症反应。总之，目前的研究结果表明，即使是短期的TAC暴露也会引起抗氧化状态和脂质过氧化的变化。因此，应考虑这些因素，以避免和尽量减少长期治疗过程中免疫抑制相关问题。
Tacrolimus (TAC) is an immunosuppressive drug, optimally used for liver, kidney, and heart transplant to avoid immune rejection. In retrospect, a multitude of studies have reported effects of TAC, such as nephrotoxicity, diabetes, and other complications. However, limited information is available regarding short-term exposure of TAC on the liver. Therefore, the present study was designed to unravel the effects of short-term exposure of TAC on a rat model. The animal model was established by TAC administration for 6, 12, 24, and 48 h time points. Liver histopathological changes were observed with PAS-D, reticulin stain, and immunostaining of PCNA and CK-7 coupled with glycogen quantification in a liver homogenate. TUNEL assay was performed to evaluate the DNA damage in the liver. Concentration of GSH and activities of SOD and CAT in the serum were measured to assess the antioxidant status, whereas liver tissue MDA level was measured as a biomarker of oxidative stress. Hepatic gene expression analysis of IL-10, IL-13, SOCS-2, and SOCS-3 was performed by RT-PCR. Results revealed marked changes in liver architecture of all TAC-treated groups, as evidenced by sinusoid dilation, hepatocyte derangement, glycogen deposition, and collapsed reticulin fibers. Significant increase in PCNA and CK-7 immunostaining along with the presence of TUNEL-positive cells was revealed in treatment groups as compared to the control group. Serum antioxidant enzyme status was markedly decreased, whereas the liver MDA level was increased in TAC treatment groups indicating oxidative stress induction. The gene expression profile of cytokines was significantly upregulated in treatment groups highlighting an inflammatory response. In conclusion, results of the current study propose that even a short-term TAC exposure can induce change in antioxidant status and lipid peroxidation. Therefore, these factors should be considered to avoid and minimize immunosuppression-related issues in a prolonged course of treatment.
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影响因子：
1.6
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