ABSTRACT
Acrylamide (AA) is a heat-induced food contaminant, mainly metabolized by the liver. Increasing evidences have proved that ferroptosis is linked to the pathogenesis of liver disease. In the current study, the underlying mechanism of AA-induced rat hepatic stellate (HSC-T6) cells ferroptosis was investigated by detecting changes in iron levels, expressions of ferroptosis-related proteins and indicators of mitochondrial dysfunction. The results showed that AA treatment led to iron levels increased and expressions of long-chain acyl-CoA synthase 4 (ACSL4), cyclooxygenase 2 (COX2) and ferritin heavy chain 1 (FTH1) proteins in HSC-T6 cells were all altered. Treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) markedly reversed the impact of AA, suggesting that AA induced ferroptosis in HSC-T6 cells. Mechanistically, AA induced the onset of ferroptosis by affecting XCT-GSH-GPX4 antioxidant signaling. Moreover, AA created a peroxidative environment for ferroptosis by inducing oxidative stress in HSC-T6 cells through mitochondrial dysfunction, as evidenced by increased mitochondrial ROS (mtROS) release, mitochondrial membrane potential (MMP) depolarization, and decreased mitochondrial ATP. Our results indicated that AA resulted in mitochondrial dysfunction and ferroptosis, and dysregulation of XCT-GSH-GPX4 antioxidant signaling was a key factor in AA-induced ferroptosis.
Subject(s)
Ferroptosis , Acrylamide/toxicity , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Iron/metabolism , Mitochondria/metabolism , RatsABSTRACT
OBJECTIVE To study the pharmacokinetics and tissue distribution of deferiprone (DFP) in rats. METHODS Plasma and tissues were collected after male Wistar rats were ig given DFP 35, 70 and 140 mg·kg~(-1) at different time points. The DFP in plasma and tissues was determined by high performance liquid chromatography. The compartment model was fitted and pharmacokinetic parameters were calculated by DAS 2.0. RESULTS The results showed that the pharmacokinetic process of DFP in rats was two-compartment model after rats were ig given DFP 35, 70 and 140 mg·kg~(-1). The t_(1/2α) were 23.3, 22.2 and 20.9 min, respectively. The t_(1/2β) were 53.3, 50.9 and 46.3 min, respectively. The Cl were 0.017, 0.021 and 0.016 L·min~(-1)·kg~(-1), respectively. The content of DFP was high in stomach and liver tissues after rats were ig given DFP 70 mg·kg~(-1), and it was lower in the other tissues. The content of DFP in liver tissues was (359.22±31.16)μg·g~(-1), at 60 min after rats were ig given DFP 70 mg·kg~(-1). CONCLUSION The absorption and elimination of DFP are quick and the tissue distribution of DFP is wide in vivo.
ABSTRACT
Objective To investigate and analyze the constitution and health condition of senior high school graduate students,and to find methods to improve and promote teenagers' health.Methods Seventy-four thousand six hundred and twenty-four senior high school students graduated from the vear 2003 to 2007 were taken the health examination according to common university and college recruitment examination standard by special medical personnel.The whole data were statistically analyzed.Results The data showed that there were 30 cases of acute viral hepatitis,41 cases of infiltrative pulmonary tuberculosis,5 cases of congenital heart diseases,the rate of hepatitis B virus(HBV)infection was 9.0%(6959/74 624),nearsightedness 82.0%(61 082/74 624);and that the rate of purely qualification,unqualified quantity and specialty limit rate(contain Single disease accumulated) for registering was 14.0%,72 cases and 93.0%(69 593/74 624) respectively.Conclusion The constitution of senior high school graduate students was unsatisfactory.
