Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats
Protective effects of fermented filtrate from Antrodia camphorata in submerged culture against CCl4-induced hepatic toxicity in rats
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DOI：
10.1021/jf0209701
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发表时间：
2003-03-12
影响因子：
6.1
通讯作者：
Yen, GC
中科院分区：
文献类型：
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作者：
Song, TY;Yen, GC
研究了樟树发酵滤液(DMF)对过氧化氢(H_2O_2)和四氯化碳(CCl4)诱导的大鼠肝细胞毒性的保护作用及其可能机制。结果表明，在AAPH/亚油酸体系中，DMF及其粗品三萜类化合物对脂质过氧化的抑制作用呈剂量-反应关系。用0.10 mg/mLDMF处理细胞4h，再用过氧化氢(100，um)处理1h，脂质过氧化作用显著降低(p<；0.05)，丙二醛生成减少。单次注射40%CCl4(10ml/100g体重，ip)前连续5d灌胃DMF[0.25和0.50 mg/kg体重]可显著抑制肝酶标记物(丙氨酸和天冬氨酸氨基转移酶)水平的升高和肝脏脂质过氧化(p<；0.05)。大鼠肝脏病理组织学评价显示，DMF可降低CCl4所致大鼠肝脏损伤的发生率，包括中性粒细胞浸润、水肿性肿胀和坏死。此外，大鼠口服前DMF中还原型谷胱甘肽依赖酶(谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽S转移酶)和谷胱甘肽/谷胱甘肽比值显著提高(p<；0.01)。结果提示，DMF可能通过上调肝脏GSH依赖酶来维持正常的GSH/GSSH比值，清除CCl4代谢过程中形成的自由基，从而起到预防生命系统氧化损伤的作用。
The protective effects and the possible mechanisms of dry matter of fermented filtrate (DMF) from Antrodia camphorata in submerged culture (ACSC) on H2O2-induced cytotoxicity in HepG2 and carbon tetrachloride (CCl4)-induced hepatotoxicity in Sprague-Dawley rats were investigated. The results showed that the inhibitory effect of DMF and its crude triterpenoids on lipid peroxidation occurred in a dose-response manner in an AAPH/linoleic acid system. When HepG2 cells were pretreated with DMF at the concentration of 0.10 mg/mL for 4 h and then induced by 1 h of treatment with H2O2 (100,uM), lipid peroxidation was significantly (p < 0.05) decreased, as measured by the formation of malondialdehyde. The oral pretreatment with DMF [0.25 and 0.50 mg/kg of body weight (bw)] for 5 consecutive days prior to the administration of a single dose of 40% CCl4 (10 ML/100 g of bw, ip) significantly prevented the increase in serum levels of hepatic enzyme markers (alanine and aspartate aminotransferase) and liver lipid peroxidation (p < 0.05). Histopathological evaluation of the rat liver revealed that DMF reduced the incidence of liver lesions, including neutrophil infiltration, hydropic swelling, and necrosis induced by CCl4 in rats. Moreover, reduced glutathione (GSH)-dependent enzymes (glutathione peroxidase, glutathione reductase, and glutathione S-transferase) and the GSH/GSSG ratio were significantly improved in the oral pretreatment DMF of rats (p < 0.01). The results suggest that DMF may play a role in preventing oxidative damage in living systems by up-regulating hepatic GSH-dependent enzymes to preserve the normal GSH/GSSH ratio and scavenging free radicals formed during CCl4 metabolism.