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The Protective Effect Of Maltol On Hepatotoxicity And Cardiotoxicity Via PI3K/Akt Signaling Pathway In Mice

Posted on:2020-05-29Degree:MasterType:Thesis
Country:ChinaCandidate:X J MiFull Text:PDF
GTID:2404330599962771Subject:Pharmacy
Abstract/Summary:
Red ginseng is the processed product of the ginseng of the Araliaceae plant.The heat-processed red ginseng undergo a chemical reaction,in which a more complex Maillard reactions occur between the maltose and amino acid,thereby producing one of the unique components of red ginseng-maltol.In recent years,more and more studies have confirmed the free radical scavenging ability of maltol,which can not only improves oxidative stress-induced neuronal damage,but also inhibits oxidative stress-induced diabetic kidney damage and improves cisplatin-induced renal cell apoptosis by the PI3k/Akt signaling pathway.In this study,we analyzed maltol which is isolated from red ginseng.Meanwhile,we established three kinds of toxicological model,the PI3K/Akt signaling pathway was used as a research object to investigate how maltol can play a protective role in liver and heart tissues by regulating apoptosis signals.1.Hepatic fibrosis is a progressive asymptomatic pathological process as a result of chronic liver injury and can progress to cirrhosis even hepatocarcinoma and play an important role in wound tissue remodeling and healing mechanism.If the process of fibrosis persists for a long time,it will develop into cirrhosis,endangering the life of the patient.In the present study,we used the intraperitoneal injection of TAA to cause the hepatic fibrosis.Results indicated that TAA intraperitoneal injection significantly increased serum activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST),these elevations were significantly diminished by pretreatment with maltol.Additionally,maltol ameliorated TAA-induced oxidative stress and restored liver histology accompanied with the decreased of α-smooth muscle actin(α-SMA)expression.Furthermore,maltol significantly suppressed the transforming growth factor-β1(TGF-β1)expression and the PI3K/Akt pathway.This study suggested that maltol alleviated experimental liver fibrosis by suppressing the activation of HSCs and inducting apoptosis of activated HSCs through TGF-β1-mediated PI3K/Akt signing pathway besides anti-oxidative stress.2.In order to investigate the regulation of maltol on apoptosis in different tissues,this study established the models of cisplatin-evoked cardiotoxicity in vivo and in vitro.Increased oxidative stress,inflammation and apoptosis have been implicated in the cardiotoxicity that limits the clinical use of cisplatin as an antitumor drug.In the present study,mice were administered intragastrically with maltol at the different dose daily.The mice in cisplatin group and maltol administration groups received four times intraperitoneal injection of cisplatin with 3 mg/kg on the 7th,9th,11 th,13th,day 1 h after the administration of maltol to induce cardiotoxicity in mice.Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with significant histopathology and elevation of serum activities of Lactate dehydrogenase(LDH),Creatine kinase(CK),Creatine kinase isoenzyme MB(CK-MB)and plasma cardiac troponin T(cTnT)concentration,cisplatin also impaired antioxidative defense system,and maltol significantly attenuated the cisplatin-evoked disturbances in the above-mentioned parameters.Pretreatment with maltol significantly attenuated oxidative stress-related apoptosis in myocardial tissue by attenuating the inhibitory effect of cisplatin on the PI3K/Akt signaling pathway,suggesting that maltol can improve cisplatin-induced apoptosis by regulating the PI3K/Akt pathway.In addition,we established a model of H9c2 cell.The cell viability was measured by MTT assay and the accumulation level of reactive ROS was evaluated by ROS fluorescence staining.Western blot was used to investigate the expression of apoptotic signaling pathway-related proteins in H9c2 cells,and further confirmed the results of mice in vivo studies.Taken together,in the above two different types of toxicology experiments,Maltol regulates apoptotic proteins by the PI3K/Akt signaling pathway,exerting its liver protection and cardioprotective effects.This suggests that the better biological activity of red ginseng may be related to the production of maltol and participate in the overall biological activity of red ginseng,the possible molecular mechanism is achieved by regulating PI3K/Akt-mediated apoptotic signaling pathway.Meanwhile,as a food additive,the safety of maltol has been recognized worldwide,and it has the advantages of low price and easy synthesis.If it can be better applied to the field of health care,it will have important clinical significance.
Keywords/Search Tags:Maltol, Liver fibrosis, Myocardial toxicity, PI3K/Akt signaling pathway, Apoptosis
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