Cytoplasmic enzyme activities involved in energy and amino acid metabolism in pathological human renal cortex

Enzyme levels of lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in the cytosol of renal cortex samples from either normal and pathologic kidney tissue. The mean enzyme activity values, expressed in Units per gram of cytosolic protein decreased in the following order: normal cortex (LDH = 4,299 +/- 654; AST = 522 +/- 101; ALT = 197 +/- 44). chronic pyelonephritis (LDH = 2,360 +/- 876; AST = 297 +/- 117; ALT = 90 +/- 48), hydronephrosis (LDH = 2,208 +/- 1,264; AST = 279 +/- 165; ALT = 82 +/- 61), pyonephrosis (LDH = 1,410 +/- 596; AST = 158 +/- 69; ALT = 23.4 +/- 16.4) and renal tuberculosis (LDH = 1,149 +/- 481; AST = 93 +/- 34; ALT = 5.6 +/- 2.8). The decrease in the enzyme activities paralleled tissue damage and it was shown to affect cellular functionality in relation with energy and amino acid metabolism.     

High adiponectin and TNF-alpha levels in moderate drinkers suffering from liver steatosis: comparison with non drinkers suffering from similar hepatopathy

Moderate alcohol consumption is associated with increased insulin sensitivity and a reduced risk for type 2 diabetes. An important endogenous mediator of insulin sensitivity is adiponectin (AN), an adipokine that displays numerous antiatherogenic, antidiabetogenic and antiinflammatory effects. Recently, acute increase in alcohol consumption has been shown to be associated with increase in plasma adiponectin and, concomitantly, insulin sensitivity. Whether chronic alcohol consumption predicts an increase in plasma AN and whether this is independent of adiposity, markers of liver dysfunction, and plasma adipokines such as tumor necrosis factor (TNF)-alpha is not known. We, therefore, investigated these relationships in 75 men who were diagnosed with liver steatosis using ultrasound/liver biopsy. We examined 75 men, who were diagnosed for having liver steatosis (ultrasound/liver biopsy). Each filled in a questionnaire on alcohol intake. Subjects were divided into two subgroups according to alcohol history and CDT concentrations--drinkers and non-drinkers. All individuals were examined for serum concentrations of AN, glucose, triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate transferase (GMT) activity; carbohydrate-deficient transferrin (CDT%) a marker of chronic alcohol consumption, insulin and TNF-alpha. The Quicki insulin sensitivity index was calculated. Forty-eight individuals were found to be moderate drinkers and 27 subjects non-drinkers. Moderate drinkers had significantly higher concentrations of AN (13.8 +/- 3,7 versus 9.1 +/- 5.4 mg/l, means +/- SD, p = 0.012) compared with non-drinkers, independent of adiposity. Plasma AN concentrations in the whole group were positively correlated with TNF-alpha concentrations (r = 0.6; p = 0.0001), CDT (r = 0.26; p = 0.0084), AST/ALT index (r = 0.3, p = 0.009), AST (r = 0.29; p = 0.011) and GMT (r = 0.29; p = 0.011) and negatively with BMI (r = -0.48; p = 0.0002) and glycemia (r = -0.22; p = 0.049). The positive associations of AN with TNF-alpha (0.8; p = 0.001), CDT (0.55; p = 0.017), AST/ALT index (0.55; p = 0.019) and the negative correlation with glycemia (-0.35; p = 0.0158) were independent of BMI. Stratified according to alcohol intake, in moderate drinkers, a positive correlation was found between AN and TNF-alpha concentrations (r = 0.6, p = 0.0001, AST/ALT index (r = 0.34, p = 0.0295) whereas in non-drinkers no such correlations were found. The concentration of AN and BMI displayed a negative correlation in both drinker and nondrinker patients (r = -0.42, p = 0.01 and -0.61; p = 0.012, respectively). We concluded that plasma AN is higher in moderate drinkers compared to non-drinkers, even after correction for BMI. Drinkers suffering from liver steatosis were found to have a positive correlation between AN concentrations, laboratory markers of liver disease and TNF-alpha. Such correlation was absent in non-drinkers suffering from liver steatosis. This suggests that alcohol may modulate the inhibitory effect of TNF-alpha on AN production, and thus, increase its plasma concentrations.     

Individual differences in plasma ALT, AST and GGT: contributions of genetic and environmental factors, including alcohol consumption

The causes of individuality of the plasma enzymes alanine aminotransferase (ALT; EC 2.6.1.2), aspartate aminotransferase (AST; EC 2.6.1.1) and gamma-glutamyl transferase (GGT; EC 2.3.2.2) were investigated in a study of 206 pairs of twins. Between-person variance was greater in men than women, while within-person variation was similar in both sexes. Plasma ALT and AST levels were affected by genetic factors, while GGT was affected by some environmental factor shared by co-twins. In the men, alcohol intake had a significant but small effect on all three enzyme levels, and since alcohol consumption was highly heritable, this appeared as a genetic influence on enzyme activities. The major factors involved in the observed correlations between these enzymes were a non-shared environmental factor other than alcohol affecting ALT, AST and GGT, and a genetic factor affecting only ALT and AST.     

Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women

Obesity and physical inactivity are independent risk factors for the development of nonalcoholic fatty liver disease (NAFLD). We determined the effect of endurance exercise training on hepatic lipid content and hepatic enzyme concentration in men and women. Waist circumference (WC), percent body fat (BF), computed tomography (CT) scans for liver attenuation (inverse relationship with hepatic lipid), bilirubin, alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) plasma concentrations were measured before and after 12 weeks of endurance training in 41 lean and obese men and women. Exercise training did not change liver attenuation, body weight, percent BF, bilirubin, or ALT concentration, but did lower WC (P < 0.0001), and decreased GGT in men only (P = 0.01). Obese subjects had a lower liver attenuation than lean subjects (P = 0.04). Obese women had lower ALT than obese men (P = 0.03). GGT was lower in women before and after training. WC was positively correlated with GGT (r = 0.32, P = 0.003) and ALT (r = 0.320, P = 0.004) and negatively correlated with liver attenuation (r = -0.340, P = 0.03). Percent BF was negatively correlated with bilirubin (r = -0.374, P = 0.005). Liver attenuation was negatively correlated with ALT (r = -0.405, P = 0.003). Short-term endurance training without weight loss does not alter hepatic lipid content. There was a strong relationship between GGT/ALT and body composition (percent BF) as well as between ALT and hepatic lipid content.     

Liver enzymes as a predictor for incident diabetes in a Japanese population: the Hisayama study

Objective: We studied the relationship between liver enzymes and the development of diabetes in a general Japanese population. Research Methods and Procedures: A total of 1804 non‐diabetic subjects 40 to 79 years of age were followed‐up prospectively for a mean of 9.0 years. Results: During the follow‐up, 135 subjects developed diabetes. In both sexes, the age‐adjusted cumulative incidence of diabetes increased significantly with elevating quartiles of serum γ‐glutamyltransferase (GGT) and alanine aminotransferase (ALT) levels. This pattern was also observed in aspartate aminotransferase (AST) quartiles for men but not for women. In multivariate analyses after adjusting for comprehensive risk factors and other liver enzymes, the risk of developing diabetes was significantly higher in the highest GGT quartile than in the lowest quartile [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.03 to 6.26 for men; OR, 5.73; 95% CI, 1.62 to 20.19 for women]. Similar results were observed in ALT quartiles (OR, 2.32; 95% CI, 0.91 to 5.92 for men; OR, 4.40; 95% CI, 1.38 to 14.06 for women) but not in AST quartiles in either sex. Significant positive associations of GGT and ALT with diabetes were seen within each stratified category of risk factors, namely fasting insulin, BMI, waist‐to‐hip ratio, high‐sensitivity C‐reactive protein, and alcohol consumption. In receiver operating characteristic analyses, the areas under the receiver operating characteristic curve of GGT and ALT were significantly larger than that of AST, fasting insulin, waist‐to‐hip ratio, or C‐reactive protein. Discussion: Our findings suggest that serum GGT and ALT concentrations are strong predictors of diabetes in the general population, independent of known risk factors.     

Reversibility of the effects on blood cells,lipids, liver function and hormones in former anabolic-androgenic steroid abusers

BACKGROUND: In contrast to the acute effects of anabolic-androgenic steroid (AAS) abuse, the long-term risk profile of former long-term abusers (ExA) is less clear. METHODS: Blood parameters of 32 male bodybuilders and powerlifters were studied. Fifteen ExA had not been abusing AAS for at least 12-43 months on average (mean dosage 700 mg for 26 weeks per year over 9 years), 17 athletes (A) were still abusing AAS (750 mg for 33 weeks per 8 years). FINDINGS: Hemoglobin (+5%), leucocytes (+33%) and platelets (+38%) were significantly higher in A. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher, cholinesterase activity (CHE) lower in A (65+/-55, 38+/-27 and 3719+/-1528U/l) compared to ExA (24+/-10, 18+/-11 and 6345+/-975U/l; each P<0.001) with normal values for gamma-glutamyl transpeptidase (gamma-GT) and bilirubin. ALT, AST and CHE correlated significantly with the extent (duration and weekly dosage, expressed as a point score) of AAS abuse in A (r=0.68, 0.57 and -0.62; each P<0.01). Total and LDL-cholesterol were similar, HDL-cholesterol was distinctly lower in A than in ExA (17+/-11 and 43+/-11 mg/dl; P<0.001) and correlated negatively with the extent of AAS abuse (r=-0.50; P<0.05). Testosterone and estradiol were significantly higher, while LH, FSH and the sexual-hormone-binding (SHB) protein were lower in A than in ExA (each P<0.001). Two ExA had testosterone levels below the normal range. INTERPRETATION: The alterations in cell counts, HDL-cholesterol, liver function and most hormones of the pituitary-testicular axis induced by a long-term abuse of AAS were reversible after stopping the medication for over 1 year. In some ExA, an increased ALT activity and a depressed testosterone synthesis were found.     

Effect of vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C

OBJECTIVES: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. METHODS: Seventeen HCV patients (male = 3; female = 14) of age 62 +/- 7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-alpha-tocopherol 500 mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients "T", low ALT group "L" (ALT < 70 IU/l) and high ALT group "H" (ALT > 70 IU/l), respectively. RESULTS: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p < 0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p < 0.0001) from the 1st to 3rd month in all three T, H and L groups. CONCLUSION: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels > 70 IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.     

Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men.

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.     

Effect of low birth weight on adrenal steroids and carbohydrate metabolism in early adulthood

AIM: Data are inconsistent whether hyperinsulinemia might be associated with adrenal hyperandrogenism in young adults born with low birth weight (LBW). METHOD: We investigated the insulin and adrenal steroid production of 70 young LBW adults [33 women (birth weight: 1,795 +/- 435 g) and 37 men (birth weight: 1,832 +/- 337 g)]. Their results were compared to those of 30 controls (14 men, 16 women), born with normal weight. RESULTS: In LBW women, we measured higher basal DHEA (33.5 +/- 13.1 vs. 23.6 +/- 8.7 nmol/l, p < 0.05), DHEAS (8.0 +/- 2.3 vs. 6.3 +/- 2.1 micromol/l, p < 0.05), androstenedione (8.3 +/- 2.8 vs. 6.0 +/- 2.2 nmol/l, p < 0.05) and cortisol (0.25 +/- 0.07 vs. 0.20 +/- 0.07 micromol/l, p < 0.05) levels and higher insulin response during oral glucose tolerance test (log.AUCins: 2.62 +/- 0.06 vs. 2.57 +/- 0.03, p < 0.05). DHEA levels correlated with fasting insulin levels (r = 0.45, p < 0.01) and insulin response (r = 0.33, p < 0.05). In LBW men, higher cortisol (0.27 +/- 0.06 vs. 0.22 +/- 0.06 micromol/l, p < 0.01) and SHBG (18.4 +/- 10.4 vs. 12.7 +/- 5.9 nmol/l, p < 0.05) levels were found. CONCLUSIONS: Our results suggest that modest hypercortisolism is present in young LBW adults. While the endocrine sequel of hypercortisolism raised insulin response and hyperandrogenism is detectable in apparently healthy young LBW women, it is absent in young LBW men. This suggests that gender-dependent mechanisms might play a role in the development of insulin resistance in LBW adults.     

Effect of envenomation on enzymes of brain of albino rats

Effects of high doses of cobra venom, (150 micrograms/120 +/- 20 g body wt) and viper venom (300 micrograms/120 +/- 20 g body wt) on aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), acetylcholinesterase (ACh) and alkaline phosphatase (ALP) of brain of albino rats were studied. While AST, LDH, ACh and ALP activities increased in both viper and cobra venom treated rats, ALT decreased in both groups compared to control.     

Hyperlipoproteinemia impairs endothelium-dependent vasodilation

Atherogenic lipoproteins can cause endothelial dysfunction in the initial stage of atherogenesis. In our study we examined 134 patients with defined hyperlipoproteinemia (non-HDL cholesterol>4.1 mmol/l or triglycerides>2.5 mmol/l or taking any of lipid lowering drugs)--94 men and 40 women. The subgroup of controls of comparable age contained 54 normolipidemic individuals--30 men and 24 women. Patients with hyperlipoproteinemia revealed significantly lower ability of endothelium-dependent flow-mediated vasodilation (EDV) measured on brachial artery (4.13+/-3.07 vs. 5.41+/-3.82 %; p=0.032) and higher carotid intima media thickness than normolipidemic controls (0.68+/-0.22 vs. 0.58+/-0.15 mm; p=0.005). In regression analysis, EDV correlated significantly with plasma concentrations of oxLDL (p<0.05) HDL-cholesterol (p<0.05), Apo A1 (p<0.05), ATI (p<0.01) and non-HDL cholesterol (p<0.05). Patients with hyperlipoproteinemia showed higher plasma levels of oxLDL (65.77+/-9.54 vs. 56.49+/-7.80 U/l; p=0.015), malondialdehyde (0.89+/-0.09 vs. 0.73+/-0.08 micromol/l; p=0.010) and nitrites/nitrates (20.42+/-4.88 vs. 16.37+/-4.44 micromol/l; p=0.018) indicating possible higher long-term oxidative stress in these patients.     

Hypertension and its related factors in Taiwanese elderly people

BACKGROUND: Our study used data collected in Chung-Hsing Village in May 1998 to evaluate the prevalence of hypertension and its correlates in Taiwanese elderly people. METHODS: All of individuals aged 65 and over were recruited as study subjects. A total of 1,093 persons, out of 1,774 registered residents, were contacted by face-to-face interview The response rate was 61.6 percent. However, only 586 respondents had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. In order to study the significant correlates of hypertension, the t-test, chi-square analysis, and multivariate logistic regression were used. RESULTS: Our results showed that 66 percent were men and 34 percent were women. The mean age was 73.1 +/- 5.3 years. The proportions of hypertension were 53.09 percent in men and 56.06 percent in women (p > 0.05). After controlling the other covariates, the multivariate logistic regression analysis showed that the significant related factors of hypertension were obesity (OR = 1.88, 95 percent CI = 1.06-3.34, p < 0.05) and renalfunction impairment (OR = 1.69, 95 percent CI = 1.02-2.80, p < 0.05). CONCLUSIONS: The prevalence of hypertension was high in elderly people. Hypertension is significantly associated with obesity and renalfunction impairment in elderly people.     

Is Alanine Aminotransferase Associated with Osteopenia in Middle-Aged and Elderly Chinese?

ObjectivesTo investigate the association between alanine aminotransferase (ALT) levels and risk of osteopenia in middle-aged and elderly Chinese with ALT within the normal range.MethodsThis was a cross-sectional study. A total of 4,890 men and women (pre- and postmenopausal) aged 40 years or older were randomly recruited from Fujian, China. Each participant was required to complete a questionnaire and then undergo anthropometric, biochemical, and bone mineral density measurements.ResultsThe odds ratio of osteopenia decreased significantly with increasing ALT level at baseline. The three groups (men, pre- and postmenopausal women) were divided by ALT quartiles. In multiple logistic regression models using the first quartile as the reference, after adjusting for corresponding confounding factors, the odds ratios of osteopenia across the other ALT quartiles were 0.576 (95% confidence interval [CI], 0.390 to 0.851), 0.654 (95% CI, 0.460 to 0.930), and 0.629 (95% CI, 0.427 to 0.926) for premenopausal women, and 0.949 (95% CI, 0.699 to 1.289), 0.733 (95% CI, 0.540 to 0.995), and 0.692 (95% CI, 0.508 to 0.943) for postmenopausal women (not significant for quartile 2). However, no significantly different results were found in men. Multiple linear regression models showed that serum ALT concentrations were positively associated with the homeostasis model assessment of insulin resistance.ConclusionOur study of middle-aged and elderly Chinese men and women demonstrates that the prevalence of osteopenia is inversely associated with ALT level when ALT is within the normal range. (Endocr Pract. 2014;20: 775-784)     

Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.     

Circulating soluble CD36 is a novel marker of liver injury in subjects with altered glucose tolerance

Liver injury linked to insulin resistance is characterized by mild to moderate increases in aminotransferase activity. A soluble form of CD36 (sCD36) was recently identified in human plasma. The aim of this study was to evaluate the relationships among plasma sCD36, insulin sensitivity (SI) and indicators of liver health. We evaluated a cohort of men from the general population (n=117). As expected, serum (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were associated positively with body mass index (BMI) and age and negatively with SI (minimal model method). Circulating sCD36 was positively associated with ALT, AST and GGT in subjects with altered glucose tolerance, but not in those with normal glucose tolerance. The difference in the slope of the relationships was significant (P=.01). Age, BMI and triglycerides (but not sCD36) contributed independently to 29% of ALT variance in subjects with normal glucose tolerance. In contrast, SI and sCD36 contributed independently to 39% of ALT variance in subjects with altered glucose tolerance. The correlation between ALT activity and sCD36 was confirmed in an independent, replication study. In summary, circulating sCD36 could represent a novel marker of liver injury in subjects with altered glucose tolerance.     

Correlation between serum alkaline phosphatase activity and blood glucose levels

Fasting blood glucose levels and serum alkaline phosphatase activity of age-matched Libyan diabetic men (168) and women (168) were determined. The mean levels of blood glucose of men and women were 227 +/- 6 and 237 +/- 5 mg/dl, respectively. The respective values of serum alkaline phosphatase were 179 +/- 5 and 199 +/- 6 IU/l. The mean serum phosphatase activity of women was significantly higher (p less than 0.001) than that of their male counterparts. A statistically significant positive correlation was found between serum alkaline phosphatase and blood glucose levels of these diabetic patients (r = 0.35; p less than 0.001).     

自噬抑制剂氯喹对急性酒精诱导小鼠肝损伤的影响

目的：探讨自噬抑制剂氯喹（CQ）对急性酒精诱导肝损伤的影响及其作用机制。方法：将雄性C57BL/6小鼠随机分为3组：正常对照组、酒精组、氯喹干预组（n=7）,其中酒精组按4.5 g/kg剂量给予33%（V/V）酒精灌胃。HE和油红O染色检测各组小鼠肝组织脂滴变化;检测肝组织甘油三酯（TG）含量变化;检测血清谷草转氨酶（AST）和谷丙转氨酶（ALT）活性;免疫荧光法检测微管相关蛋白轻链3（LC3）蛋白变化;Western blot法检测LC3蛋白和核蛋白P65表达的变化;ELISA法检测促炎因子TNF-α、IL-6的变化。结果：与对照组比较,酒精组脂滴形成、TG含量、血清AST和ALT活性明显增高。与对照组比较,酒精组LC3-Ⅱ蛋白表达明显增加;与酒精组比较,氯喹干预组使酒精诱导的LC3-Ⅱ蛋白表达增强进一步加剧,使酒精诱导的TG含量、血清AST和ALT活性进一步增高,同时增加了酒精诱导的p65入核及TNFα、IL-6释放。结论：急性酒精能引起小鼠肝脏脂肪变化及炎症,而自噬抑制剂氯喹抑制自噬进程,加剧酒精诱导的肝损伤,说明自噬在酒精诱导肝损伤中可能具有保护效应。     

Biochemical stress indicators of greater wax moth exposure to organophosphorus insecticides

Although acetylcholinesterase (AChE) is the primary target of organophosphorus insecticides (OPs), increasing evidence regarding their secondary effects suggests that OPs disturb homeostasis of insects by generating free radical intermediates that trigger lipid peroxidation. We therefore investigated alterations in lipid peroxidation product, malondialdehyde (MDA) content, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, in conjunction with AChE activity as biochemical stress indicators in greater wax moth, Galleria mellonella (L.) larvae for OPs methyl parathion (MP) and ethyl parathion (EP). The effects of MP and EP were first investigated by rearing the young larvae on an artificial diet containing 0.01, 0.1, 1, 10, and 100 ppm of each insecticide. Second, the mature larvae were injected with 0.05, 0.5, 5, 50, and 500 ng of insecticides for determining the changes in biochemical stress responses. The diet with lowest level of MP significantly decreased the activities of all measured enzymes, whereas it increased MDA content. However ALT and AST were significantly higher in the larvae reared with the diet with high levels of MP than in control larvae. All tested levels of MP resulted in a decrease in AChE activity. The lowest level of EP in diet (0.01 ppm) significantly increased ALT activity, whereas it reduced that of AChE. This insecticide at 0.1 ppm resulted in reduced AST activity, but 1 ppm in diet elevated AST activity and MDA content. EP at 0.1 ppm and higher levels in the diet reduced ALT activity. All dietary EP levels significantly decreased AChE activity. ALT, AST, and AChE were lower in larvae fed with the diet containing 100 ppm ethyl parathion compared with larvae on control diet. MP at 50 ng per larva increased ALT and AST activities from 35.42 +/- 0.74 and 26.34 +/- 0.83 to 203.57 +/- 1.09, and 122.90 +/- 1.21 U/g, respectively, when the mature larvae were injected. All injected doses of EP dramatically reduced both ALT and AST activities, but only the lowest and highest levels of this insecticide decreased AChE activity. The lowest level of this insecticide also significantly increased MDA content in larvae. High levels of both insecticides increased MDA content. We observed a significant higher increase in MDA content in the larvae reared with 10 ppm EP (102.16 +/- 1.57 nmol/g protein) than the control group (30.28 +/- 1.42 nmol/g protein). These results suggest that OPs caused the metabolic and synaptic dysfunctions in greater wax moth and alter its biochemical physiology in response to oxidative stress.     

Astringinin-mediated attenuation of the hepatic injury following trauma-hemorrhage

Although astringinin administration under adverse circulatory conditions is known to be protective, the mechanism by which astringinin produces the salutary effects remains unknown. We hypothesize that astringinin administration in males following trauma-hemorrhage decreases cytokine production and protects against hepatic injury. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min, then resuscitation). Different doses of astringinin (0.01, 0.03, 0.1, 0.3 mg/kg of body weight) or vehicle were administered intravenously during resuscitation. Concentrations of plasma aspartate aminotransferase (AST) with alanine aminotransferase (ALT) and various hepatic parameters were measured (n = 8 rats/group) at 24 h after resuscitation. One-way ANOVA and Tukey testing were used for statistical analysis. Trauma-hemorrhage significantly increased plasma AST and ALT levels at 24 h postresuscitation; there was a dose-related benefit when astringinin was administered at doses of 0.01 to 0.3 mg/kg. In astringinin-treated (0.3 mg/kg) rats subjected to trauma-hemorrhage, there were significant improvements in liver myeloperoxidase (MPO) activity (237.80 +/- 45.89 vs. 495.95 +/- 70.64 U/mg protein, P < 0.05), interleukin-6 (IL-6) levels (218.54 +/- 34.52 vs. 478.60 +/- 76.21 pg/mg protein, P < 0.05), cytokine-induced neutrophil chemoattractant (CINC)-1 (88.32 +/- 20.33 vs. 200.70 +/- 32.68 pg/mg protein, P < 0.05), CINC-3 (110.83 +/- 26.63 vs. 290.14 +/- 76.82 pg/mg protein, P < 0.05) and intercellular adhesion molecule (ICAM)-1 concentrations (1,868.5 +/- 211.5 vs. 3,645.0 +/- 709.2 pg/mg protein, P < 0.05), as well as in histology. Results show that astringinin significantly attenuates proinflammatory responses and hepatic injury after trauma-hemorrhage. In conclusion, the salutary effects of astringinin administration on attenuation of hepatic injury following trauma-hemorrhage are likely due to reduction of pro-inflammatory mediator levels.