Peroxisome Proliferator Activator Receptor (PPAR)- γ Ligand, but Not PPAR- α , Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver.
Peroxisome Proliferator Activator Receptor (PPAR)- γ Ligand, but Not PPAR- α , Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver.
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DOI：
10.1155/2014/626319
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Rifaai RA
中科院分区：
文献类型：
--
作者：
El-Sheikh AA;Rifaai RA
研究了过氧化物酶体增殖物激活物受体（peroxisome proliferator activator receptor，PPAR）-α和-γ激动剂非诺贝特（fenofibrate，FEN）和吡格列酮（pioglitazone，PIO）对环磷酰胺（cyclophosphamide，CP）诱导的大鼠肝损伤的保护作用。FEN和PIO（分别为150和10 mg/kg/天）口服给药4周。在不同的组中，CP（150 mg/kg，i. p.）在实验结束前5天以单剂量注射，有或没有任一种PPAR激动剂。CP诱导肝毒性，因为它引起组织病理学改变，血清丙氨酸和天冬氨酸转氨酶，总胆红素，白蛋白，碱性磷酸酶和乳酸脱氢酶增加。CP引起肝脏氧化应激，表明组织还原型谷胱甘肽减少，丙二醛和一氧化氮水平增加。CP还导致肝脏抗氧化酶水平降低，包括过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶。此外，CP增加血清和肝脏炎症标志物肿瘤坏死因子（TNF）-α的水平，使用ELISA评估。在CP激发前预先给予PIO而非FEN可改善肝功能和组织学，并显著逆转氧化和炎症参数。总之，通过激活抗氧化和抗炎机制，激活PPAR-γ（而非PPAR-α）可保护CP诱导的肝毒性，并可作为CP化疗期间的补充。
Hepatoprotective potential of peroxisome proliferator activator receptor (PPAR)-α and -γ agonists, fenofibrate (FEN), and pioglitazone (PIO), respectively, against cyclophosphamide (CP)-induced toxicity has been investigated in rat. FEN and PIO (150 and 10 mg/kg/day, resp.) were given orally for 4 weeks. In separate groups, CP (150 mg/kg, i.p.) was injected as a single dose 5 days before the end of experiment, with or without either PPAR agonist. CP induced hepatotoxicity, as it caused histopathological alterations, with increased serum alanine and aspartate transaminases, total bilirubin, albumin, alkaline phosphatase and lactate dehydrogenase. CP caused hepatic oxidative stress, indicated by decrease in tissue reduced glutathione, with increase in malondialdehyde and nitric oxide levels. CP also caused decrease in hepatic antioxidant enzyme levels, including catalase, superoxide dismutase, glutathione peroxidase, and glutathione S-transferase. Furthermore, CP increased serum and hepatic levels of the inflammatory marker tumor necrosis factor (TNF)-α, evaluated using ELISA. Preadministration of PIO, but not FEN, prior to CP challenge improved hepatic function and histology, and significantly reversed oxidative and inflammatory parameters. In conclusion, activation of PPAR-γ, but not PPAR-α, conferred protection against CP-induced hepatotoxicity, via activation of antioxidant and anti-inflammatory mechanisms, and may serve as supplement during CP chemotherapy.
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影响因子：
--
作者：
Hsiao PJ;Hsieh TJ;Kuo KK;Hung WW;Tsai KB;Yang CH;Yu ML;Shin SJ
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Kuttan, Girija
DOI：
10.1097/01.alc.0000192394.26573.10
发表时间：
2005-12-01
影响因子：
3.2
作者：
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通讯作者：
Sato, N
DOI：
10.1111/j.1365-2710.2009.01029.x
发表时间：
2009-10-01
影响因子：
2
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Urbanek, K.