摘要
OBJECTIVE Acetaminophen(APAP),also known as paracetamol,is a commonly used antipyretic,anal⁃gesic and anti-inflammatory drug.However,during the use of APAP for more than half a century,people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a cen⁃tury.The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use.In Chinese tra⁃ditional medicine,chrysanthemums have the functions of dispelling wind,dissipating heat,clearing the liver and improv⁃ing eyesight.Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety,it has good value for medicine and food.The aim of this study was to investigate the protective effect of Bianliang Ziyu extract(BZE)on APAP-damaged rats and the potential molecular mechanism.METHODS Male Sprague-Dawley rats(200-220 g)were intragastrically administered BZE(110,220 and 440 mg·kg^-1)for 8 d.On the ninth day,APAP(800 mg·kg^-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury.The serum and liver samples were collected after 24 h.The levels of alanine aminotransferase(ALT),aspartic aminotransferase(AST),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in serum and liver tissue of rats were detected by kit method.HE staining was used to observe the histopathological changes in the liver of rat.The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosyn⁃thesis related proteins were detected by Western blot.RESULTS The results showed that BZE significantly reduced the levels of ALT,AST,MDA and ROS and increased the levels of GSH and SOD caused by APAP.Moreover,BZE increased phosphorylation of AMP-activated protein kinase(AMPK)and glycogen synthase kinase 3β(GSK3β),promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptorγ(PPAR-γ),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),mitochondrial transcription factor(TFAM)and nuclear respira⁃tory factor 1(NRF1).CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.
OBJECTIVE Acetaminophen（APAP）, also known as paracetamol, is a commonly used antipyretic, analgesic and anti-inflammatory drug. However, during the use of APAP for more than half a century, people have not only used APAP to fight diseases but have also suffered the adverse effects brought about by APAP for more than half a century. The most serious adverse reaction to APAP is hepatotoxicity caused by overdose or long-term use. In Chinese traditional medicine, chrysanthemums have the functions of dispelling wind, dissipating heat, clearing the liver and improving eyesight. Although the chrysanthemum variety named Bianliang ziyu from Kaifeng is not a medicinal variety, it has good value for medicine and food. The aim of this study was to investigate the protective effect of Bianliang Ziyu extract（BZE） on APAP-damaged rats and the potential molecular mechanism. METHODS Male Sprague-Dawley rats（200-220 g） were intragastrically administered BZE(110, 220 and 440 mg·kg-1) for 8 d. On the ninth day, APAP(800 mg·kg-1)was administered intragastrically to the rats 0.5 h after BZE administration to induced drug-induced liver injury. The serum and liver samples were collected after 24 h. The levels of alanine aminotransferase（ALT）, aspartic aminotransferase（AST）, reactive oxygen species（ROS）, malondialdehyde（MDA）, superoxide dismutase（SOD） and glutathione（GSH） in serum and liver tissue of rats were detected by kit method. HE staining was used to observe the histopathological changes in the liver of rat. The effects of BZE on the expression of the oxidative stress related proteins and the mitochondrial biosynthesis related proteins were detected by Western blot. RESULTS The results showed that BZE significantly reduced the levels of ALT, AST, MDA and ROS and increased the levels of GSH and SOD caused by APAP. Moreover, BZE increased phosphorylation of AMP-activated protein kinase（AMPK） and glycogen synthase kinase 3β（GSK3β）, promoted the nuclear translocation of nuclear factor-erythroid 2-related factor 2（Nrf2）. BZE also upregulated the expression of mitochondrial biosynthesis related proteins such as peroxisome proliferator-activated receptor γ（PPAR-γ）, peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α）, mitochondrial transcription factor（TFAM） and nuclear respiratory factor 1（NRF1）. CONCLUSION BZE alleviates APAP-induced liver injury in rats by inhibiting oxidative stress via GSK3β-Nrf2 signaling and the mitochondrial biosynthesis pathway mediated by AMPK.
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2019年第9期719-719,共1页
Chinese Journal of Pharmacology and Toxicology
