BACKGROUND:Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions.Although decompression of the bile duct has been reported to improve liver functions in animal studi...BACKGROUND:Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions.Although decompression of the bile duct has been reported to improve liver functions in animal studies,the mechanism of obstruction differs from that in humans.This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting.METHODS:We conducted a 'before and after study' on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression.Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling(TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin(HE) to identify bile lakes.All measurements were independently done by 2 observers.RESULTS:Twenty-one severe obstructive jaundice patients were included.In all patients,excessive hepatocyte apoptosis and bile lakes were apparent.After decompression,the hepatocyte apoptosis index decreased from 53.1(SD 105) to 11.7(SD 13.6)(P<0.05),and the bile lakes from 23.6(SD 14.8) to 10.9(SD 6.9)(P<0.05).CONCLUSION:Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice,similar to the findings in animal studies.展开更多
BACKGROUND:Increasing evidence suggests that the inactivation of cathepsin B attenuates hepatocyte apoptosis and liver damage.This study aimed to investigate the protective effects of a cathepsin B inhibitor(CA-074me)...BACKGROUND:Increasing evidence suggests that the inactivation of cathepsin B attenuates hepatocyte apoptosis and liver damage.This study aimed to investigate the protective effects of a cathepsin B inhibitor(CA-074me) on lipopolysaccharide(LPS)/D-galactosamine(D-GalN)-induced acute hepatic failure(AHF) in mice.METHODS:Mice were intraperitoneally injected with a combination of LPS/D-GalN to induce AHF with or without CA-074me pretreatment.The cumulative survival rates were calculated 48 hours after the induction of AHF.As well as changes in biochemical indicators and liver histology,hepatocyte apoptosis was assessed using a TUNEL method.Serum tumor necrosis factor-α(TNF-α) production,caspase-3,caspase-8,and caspase-9 activity was evaluated.Cytosolic cytochrome c and Bcl-2 expression were measured by Western blotting.RESULTS:The marked elevation in serum aminotransferase activity and prothrombin time found in LPS/D-GalN-treated mice was significantly improved by pretreatment with CA074me.The efficacy of CA-074me was also confirmed by histological analysis and TUNEL assay.The survival rate significantly improved in LPS/D-GalN-induced mice given CA-074me compared with untreated mice.LPS/D-GalNinduced caspase-3 and caspase-9 activation was remarkably suppressed by CA-074me.However,the increased levels of serum TNF-α and elevated caspase-8 activity in AHF mice were not significantly reduced by CA-074me.Moreover,CA074me sharply reduced the increased expression of cytosolic cytochrome c and markedly augmented Bcl-2 expression.CONCLUSION:These results suggest that CA-074me has a protective effect in acute hepatic failure induced by LPS/D-GalN.展开更多
BACKGROUND Aloe vera exerts several biological activities,such as,anti-inflammatory,antioxidant,and antimicrobial effects.It was recently shown to reduce insulin resistance and triglyceride level.We hypothesized that ...BACKGROUND Aloe vera exerts several biological activities,such as,anti-inflammatory,antioxidant,and antimicrobial effects.It was recently shown to reduce insulin resistance and triglyceride level.We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH)in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n=6 in each group).Rats in the control group were fed ad libitum with a standard diet for 8 wk.Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD)for 8 wk.Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg)by gavage daily for 8 wk.Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA)levels increased significantly in the NASH group as compared with the control group(377±77 nmol/mg vs 129±51 nmol/mg protein,respectively,P<0.001).Glutathione(GSH)levels were significantly lower in the NASH group than the control group(9±2 nmol/mg vs 24±8 nmol/mg protein,respectively,P=0.001).The expression of interleukin-18 (IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisomeproliferator-activated receptor gamma decreased in the NASH group comparedwith the controls. Following aloe vera administration, MDA levels decreased (199± 35 nmol/mg protein) and GSH increased (18 ± 4 nmol/mg protein) markedly.Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyteapoptosis were observed in the NASH group. Aloe vera treatment attenuatedthese changes in liver histology.CONCLUSIONAloe vera attenuated oxidative stress, hepatic inflammation and hepatocyteapoptosis, thus improving liver pathology in rats with NASH.展开更多
Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although mos...Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although most people with dengue viral infection are asymptomatic,approximately 25%experience a selflimited febrile illness with mild to moderate biochemical abnormalities.Severe dengue diseases develop in a small proportion of these patients,and the common organ involvement is the liver.The hepatocellular injury was found in 60%-90%of DHF patients manifested as hepatomegaly,jaundice,elevated aminotransferase enzymes,and critical condition as an acute liver failure(ALF).Even the incidence of ALF in DHF is very low(0.31%-1.1%),but it is associated with a relatively high mortality rate(20%-68.3%).The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis,immunemediated hepatocyte injury induced hepatitis,and cytokine storm.Hepatic hypoperfusion is another contributing factor in dengue shock syndrome.The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.展开更多
文摘BACKGROUND:Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions.Although decompression of the bile duct has been reported to improve liver functions in animal studies,the mechanism of obstruction differs from that in humans.This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting.METHODS:We conducted a 'before and after study' on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression.Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling(TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin(HE) to identify bile lakes.All measurements were independently done by 2 observers.RESULTS:Twenty-one severe obstructive jaundice patients were included.In all patients,excessive hepatocyte apoptosis and bile lakes were apparent.After decompression,the hepatocyte apoptosis index decreased from 53.1(SD 105) to 11.7(SD 13.6)(P<0.05),and the bile lakes from 23.6(SD 14.8) to 10.9(SD 6.9)(P<0.05).CONCLUSION:Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice,similar to the findings in animal studies.
文摘BACKGROUND:Increasing evidence suggests that the inactivation of cathepsin B attenuates hepatocyte apoptosis and liver damage.This study aimed to investigate the protective effects of a cathepsin B inhibitor(CA-074me) on lipopolysaccharide(LPS)/D-galactosamine(D-GalN)-induced acute hepatic failure(AHF) in mice.METHODS:Mice were intraperitoneally injected with a combination of LPS/D-GalN to induce AHF with or without CA-074me pretreatment.The cumulative survival rates were calculated 48 hours after the induction of AHF.As well as changes in biochemical indicators and liver histology,hepatocyte apoptosis was assessed using a TUNEL method.Serum tumor necrosis factor-α(TNF-α) production,caspase-3,caspase-8,and caspase-9 activity was evaluated.Cytosolic cytochrome c and Bcl-2 expression were measured by Western blotting.RESULTS:The marked elevation in serum aminotransferase activity and prothrombin time found in LPS/D-GalN-treated mice was significantly improved by pretreatment with CA074me.The efficacy of CA-074me was also confirmed by histological analysis and TUNEL assay.The survival rate significantly improved in LPS/D-GalN-induced mice given CA-074me compared with untreated mice.LPS/D-GalNinduced caspase-3 and caspase-9 activation was remarkably suppressed by CA-074me.However,the increased levels of serum TNF-α and elevated caspase-8 activity in AHF mice were not significantly reduced by CA-074me.Moreover,CA074me sharply reduced the increased expression of cytosolic cytochrome c and markedly augmented Bcl-2 expression.CONCLUSION:These results suggest that CA-074me has a protective effect in acute hepatic failure induced by LPS/D-GalN.
基金Supported by the Grant of Ratchadaphiseksomphot,Faculty of Medicine,Chulalongkorn University,Bangkok,Thailand,No.RA59/035.
文摘BACKGROUND Aloe vera exerts several biological activities,such as,anti-inflammatory,antioxidant,and antimicrobial effects.It was recently shown to reduce insulin resistance and triglyceride level.We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH)in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n=6 in each group).Rats in the control group were fed ad libitum with a standard diet for 8 wk.Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD)for 8 wk.Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg)by gavage daily for 8 wk.Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA)levels increased significantly in the NASH group as compared with the control group(377±77 nmol/mg vs 129±51 nmol/mg protein,respectively,P<0.001).Glutathione(GSH)levels were significantly lower in the NASH group than the control group(9±2 nmol/mg vs 24±8 nmol/mg protein,respectively,P=0.001).The expression of interleukin-18 (IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisomeproliferator-activated receptor gamma decreased in the NASH group comparedwith the controls. Following aloe vera administration, MDA levels decreased (199± 35 nmol/mg protein) and GSH increased (18 ± 4 nmol/mg protein) markedly.Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyteapoptosis were observed in the NASH group. Aloe vera treatment attenuatedthese changes in liver histology.CONCLUSIONAloe vera attenuated oxidative stress, hepatic inflammation and hepatocyteapoptosis, thus improving liver pathology in rats with NASH.
文摘Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although most people with dengue viral infection are asymptomatic,approximately 25%experience a selflimited febrile illness with mild to moderate biochemical abnormalities.Severe dengue diseases develop in a small proportion of these patients,and the common organ involvement is the liver.The hepatocellular injury was found in 60%-90%of DHF patients manifested as hepatomegaly,jaundice,elevated aminotransferase enzymes,and critical condition as an acute liver failure(ALF).Even the incidence of ALF in DHF is very low(0.31%-1.1%),but it is associated with a relatively high mortality rate(20%-68.3%).The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis,immunemediated hepatocyte injury induced hepatitis,and cytokine storm.Hepatic hypoperfusion is another contributing factor in dengue shock syndrome.The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.