Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation
Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation
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DOI：
10.1016/j.lfs.2018.01.010
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发表时间：
2018-03-01
期刊：
影响因子：
6.1
通讯作者：
El-Sayed, Yasser S.
中科院分区：
文献类型：
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作者：
Khafaga, Asmaa F.;El-Sayed, Yasser S.
目的：甲氨蝶呤(MTX)是一种有效的细胞毒性药物，用于治疗多种致癌、炎性和自身免疫性疾病，但MTX的肝毒性限制了其应用。因此，本研究旨在评价螺旋藻对MTX急性毒性的保护和免疫刺激作用。主要方法：32只雄性Wistar大鼠随机分为4组(n=8)：对照组、SP组(500 mg/kg BWT，每天灌胃21天)、MTX(20 mg/kg BWT，单次ip)和MTX+SP组(n=8)。观察肝和脾的组织结构、白细胞计数和血清免疫球蛋白。检测肝脏氧化/抗氧化状态、促炎细胞因子(肿瘤坏死因子-a、白介素6)和促凋亡蛋白(caspase-3、bax)的免疫表达。主要发现：MTX可导致大鼠肝脏广泛坏死和空泡化，脾白髓淋巴组织严重萎缩，血清转氨酶、乳酸脱氢酶、肝组织丙二醛、肿瘤坏死因子-a和白介素6水平升高，caspase-3和bax阳性的肝细胞数增多。白细胞计数、血清免疫球蛋白(Ig A、Ig M和Ig G)水平以及肝脏抗氧化酶(GSH、GPX、SOD和CAT)水平也显著下降。SP可显著改善肝、脾组织结构，恢复肝酶活性，减少脂质过氧化产物、促炎性细胞因子、caspase3和Bax免疫表达。此外，抗氧化酶、血清免疫球蛋白和总白细胞计数也显著增加。意义：SP具有良好的抗氧化、抗炎、抗细胞凋亡和免疫刺激特性，可对抗MTX诱导的肝毒性和免疫抑制。
Aims: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity.Main methods: Thirty-two male Wistar rats were randomly allocated into the following four groups (n=8): control, SP (500 mg/kg bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and MTX + SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum immunoglobulins were evaluated. Hepatic oxidant/antioxidant status, proinflammatory cytokines (tumor necrosis factor-a, and interleukin 6), and pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed.Key findings: MTX induced extensive hepatic necrosis and vacuolation, and sever lymphoid depletion in splenic white pulp with increased levels of serum transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis factor-a and interleukin 6; and number of caspase 3-and Bax-positive hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins (IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and CAT) was also detected. Pretreatment with SP resulted in significant improvements in hepatic and splenic histologic architecture, as well as restoring liver enzymes and reduction of lipid peroxidation product, proinflammatory cytokines, and caspase 3 and Bax immunoexpression. Additionally, a significant increase in antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was demonstrated.Significance: SP possesses promising antioxidant, anti-inflammatory, anti-apoptotic and immune stimulatory properties against MTX-induced hepatotoxicity and immunosuppression.