螺旋藻保护大鼠免受他克莫司引起的肝和肾毒性:生化和组织学研究

Zakaria A. Elzawahry, M. Abass, M. R. A. El-Haleem, R. A. A. Hamid, H. Atteia
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引用次数: 4

摘要

他克莫司是一种强大的免疫抑制剂,具有肝毒性和肾毒性作用。它对许多有毒物质有保护作用。本研究旨在探讨螺旋藻对他克莫司所致肝、肾毒性的保护作用。40只成年雄性白化大鼠分为4组。ⅰ组为对照组,ⅱ组为螺旋藻组(口服螺旋藻500 mg/Kg体重(bw)/天),ⅲ组为他克莫司组(口服他克莫司12 mg/Kg体重/天);第六组,预防组(在他克莫司之前口服螺旋藻3天,与他克莫司同时口服螺旋藻28天,先前剂量相同)。他克莫司对肝肾功能和结构均有不良影响,表现为肝转氨酶、总胆红素和直接胆红素、白蛋白、尿素氮、血清肌酐和肌酐清除率升高。他克莫司组大鼠血清总抗氧化能力(TAC)和肝脏、肾脏总硫醇分子(TTM)显著降低,丙二醛显著升高。在组织病理学上,他克莫司引起肝细胞肿胀和肉芽化,血窦充血和胆管变性,肾小球肥大和分节,肾小管肿胀、变性和透明质化。螺旋藻预处理和协同处理显著改善了这些有害影响。与此同时,PCNA的表达部分恢复到接近正常水平。此外,螺旋藻治疗没有改变谷血他克莫司水平或他克莫司诱导的免疫抑制。需要进一步的研究来评估接受他克莫司治疗的移植患者是否可以从螺旋藻的保护作用中获益。关键词:抗氧化剂,丙二醛(MDA),总抗氧化能力(TAC),他克莫司,总硫醇分子(TTM),增殖细胞核抗原(PCNA),螺旋藻
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Spirulina protects against tacrolimus-induced hepatic and renal toxicity in rats: A biochemical and histological study
Tacrolimus is a powerful immunosuppressive agent with hepatotoxic and nephrotoxic effects. It has a protective role against many toxicants. This study was conducted to evaluate the possible protective role of spirulina against tacrolimus induced hepatotoxicity and nephrotoxicity. Forty adult male albino rats divided into 4 groups. Group I, control group, Group II, spirulina group (received spirulina 500 mg/Kg body weight (bw)/day orally), Group III, tacrolimus group (received tacrolimus 12 mg/kg bw/day orally); and Group VI, prophylactic group (orally administered spirulina for 3 days before and 28 days concurrently with tacrolimus in the same previous doses). Tacrolimus induced adverse effects on both liver and kidney functions and structure that was manifested by elevated hepatic transaminases, total and direct bilirubin, albumin, blood urea nitrogen, serum creatinine and creatinine clearance. There was a significant decrease in serum total antioxidant capacity (TAC) and hepatic and renal total thiol molecules (TTM), with a significant increase in serum malondialdehyde in tacrolimus group. Histopathologically, tacrolimus induced swelling and granulation of hepatocytes, congestion of blood sinusoids and degeneration of bile ductiles, glomerular hypertrophy and segmentation, swelling, degeneration and hyalinosis of renal tubules. Spirulina pre- and co-treatment significantly improved these deleterious effects. This was accompanied by partial restoration of the expression of PCNA near to the normal level observed in control rats. Moreover, spirulina treatment did not alter the trough blood tacrolimus levels or tacrolimus-induced immunosuppression. Further studies are warranted to evaluate whether transplant patients on tacrolimus treatment may benefit from the protective effects of spirulina. Key words: Antioxidant, malondialdehyde (MDA), total antioxidant capacity (TAC), tacrolimus, total thiol molecules (TTM), proliferating cell nuclear antigen (PCNA), spirulina.
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