Occupational perchloroethylene exposure in dry-cleaning workers: Oxidative stress and hepatorenal biomarkers

The involvement of Perchloroethylene (PCE) in the development of autoimmune diseases has been reported. However, few studies investigated immunotoxicity in PCE-exposed workers. To study changes in the oxidative stress and cytokine profile of young female dry-cleaning workers exposed to PCE. Thirty-eight exposed workers and 38 unexposed controls were recruited. All the participants were young nonsmoker females. Individual interviews were conducted by a physician. Blood samples were collected and hematological tests were performed by an automated Coulter Counter. Plasma PCE levels were determined using gas chromatography/flame ionization detection. Plasma total antioxidant capacity (TAC), Catalase (CAT), Superoxide dismutase (SOD), and Malondialdehyde (MDA) levels were measured using the colorimetric method. The levels of plasma cytokines interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by commercially kits. The levels of plasma PCE averaged 561±96 ng/ml in the exposed group compared with 1.3±0.5 ng/ml in the controls. The hematological tests failed to find abnormalities in the exposed workers. Exposed workers presented significantly increased plasma levels of MDA, SOD and CAT. There were no significant differences between the two groups for level of plasma TAC. Significantly increased plasma IL-1β and TNF-α and decreased IL-2 and IL-8 levels were seen in the exposed workers. There were no significant differences between the two groups for IL-4, IL-6, and IFN-γ. PCE exposure resulted in changed cytokine profile in dry-cleaning workers, suggesting the potential immunotoxicity of PCE at low exposure levels.

Objective To investigate the protective effect of propofol pretreatment against hepatic ischemia-reperfusion injury and oxidative stress in rats and the mechanism of the role of GSK-3β. Methods Sixty SD rats were randomly divided into four groups: sham operation group (S group), ischemia-reperfusion group (I-R group), propofol pretreatment group (P group), TDZD-8 pretreatment group (T group). The hepatic ischemia-reperfusion rat models were established by the method of Nauta. Rats were subjected to 30-min, 60-min and 90-min 70% warm ischemia of liver followed by reperfusion for 120 min, respectively. Propofol (12 mg/kg·h) was injected via femoral vein 30 min before ischemia till the end of reperfusion in P group and TDZD-8 (1 mg/ kg) were injected via femoral vein 20 min before ischemia in T group. The animals were killed at 120 min after reperfusion. Blood samples and the liver tissue were obtained. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed. Liver morphological changes were observed using optical microscopy. p-GSK-3β Ser9 and total GSK-3β expression was determined by Western blot. Results Compared with S group, AST, ALT, LDH and MDA level was increased, SOD level was reduced, and p-GSK-3β Ser9 expression was significantly reduced in I-R group. Compared with I-R group, the content of AST, ALT, LDH and MDA was reduced significantly, SOD increased significantly, and the content of p-GSK-3β Ser9 increased significantly in P group and T group. There were no significant differences between P group and T group. The hematoxylin-eosin staining of hepatic tissues revealed in I-R group had severe structural damage and periportal inflammatory cells infiltrated, hepatocyte necrosis and sinusoidal congestion. In P group and T group, liver tissues had normal structure, less cell death, edema and inflammatory cell infiltration. Conclusions Propofol can significantly reduce hepatic ischemia reperfusion injury by reducing oxidative stress and lipid hydroperoxides. This protective effect of Propofol may be associated with the inhibition of GSK-3β by GSK-3β Ser9 phosphorylation. Key words: Propofol; Oxidative stress; Liver; Ischemia-reperfusion injury; Rat

To study the effect of glucagon-likepeptide 1(GLP-1)receptor agonist on insulin resistance and hepatic oxidative stress in rats with diabetes mellitus combined with nonalcoholic fatty liver disease. 36 male SD rats were served as the experimental animal and randomly divided into control group, model group, and GLP-1 group. The rats of control group were given routine diet with intraperitoneal injection of normal saline, those in model group were given high fat diet and intraperitoneal injection of normal saline, while GLP-1 group rats were fed with high fat diet and intraperitoneal injection of liraglutide. After 4 weeks of treatment, insulin resistance, lipid metabolism, liver injury and oxidative stress were all assessed. Serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, alanine transaminase(ALT), aspartate transaminase(AST)levels and total cholesterol, triglyceride contents in liver tissue, and as well as homeostasis model assessment for insulin resistance(HOMA-IR)levels of model group were significantly higher than those of control group, complex insulin sensitivity index(ISIcomp)level was significantly lower than that of control group; serum fasting blood glucose, fasting insulin, total cholesterol, triglyceride, ALT, AST contents and HOMA-IR levels of GLP-1 group were significantly lower than those of model group, ISIcomp level was significantly higher than that of model group; superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), catalase(CAT)contents in liver tissue of model group were significantly lower, while malondialdehyde content and SOD, GSH-Px, CAT, NF-E2 related factor-2(Nrf-2), antioxidant response element(ARE), heme oxygenase-1(HO-1), quinone oxidoreductase-1(NQO-1), glutathione thiol transferase(GST)mRNA expression were significantly higher than control group; SOD, GSH-Px, CAT contents and SOD, GSH-Px, CAT, Nrf-2, ARE, HO-1, NQO-1, GST mRNA expression in the liver tissue of GLP-1 group were significantly higher, while malondialdehyde content was significantly lower than that of model group. GLP-1 receptor agonist reduces insulin resistance and liver oxidative stress injury in diabetic rats with nonalcoholic liver disease. (Chin J Endocrinol Metab, 2017, 33: 228-232) Key words: Diabetes mellitus, type 2; Nonalcoholic fatty liver disease; Glucagon like peptide -1; Insulin resistance; Oxidative stress

Effect of Ginkgo biloba on liver injury of arsenic poisoning rats caused by corn flour baked by high-arsenic coal

To investigate the role and mechanism of silent information regulator 1 (SIRT1) in regulating nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in oxidative stress and inflammatory response to sepsis-induced liver injury. A total of 24 male Sprague-Dawley (SD) rats were randomly divided into sham operation (Sham) group, cecal ligation and puncture (CLP) group, SIRT1 agonist SRT1720 pretreatment (CLP+SRT1720) group and SIRT1 inhibitor EX527 pretreatment (CLP+EX527) group, with 6 rats in each group. Two hours before operation, SRT1720 (10 mg/kg) or EX527 (10 mg/kg) were intraperitoneally injected into the CLP+SRT1720 group and CLP+EX527 group, respectively. Blood was collected from the abdominal aorta at 24 hours after modeling and the rats were sacrificed for liver tissue. The serum levels of interleukins (IL-6, IL-1β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by microplate method. Hematoxylin-eosin (HE) staining was used to observe the pathological injury of rats in each group. The levels of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH) and superoxide dismutase (SOD) in liver tissue were detected by corresponding kits. The mRNA and protein expressions of SIRT1, Nrf2 and HO-1 in liver tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Compared with the Sham group, the serum levels of IL-6, IL-1β, TNF-α, ALT and AST in the CLP group were significantly increased; histopathological results showed that liver cords were disordered, hepatocytes were swollen and necrotic, and a large number of inflammatory cells infiltrated; the contents of MDA and 8-OHdG in liver tissue increased, while the contents of GSH and SOD decreased; and the mRNA and protein expressions of SIRT1, Nrf2 and HO-1 in liver tissues were significantly decreased. These results suggest that sepsis rats have liver dysfunction, and the levels of SIRT1, Nrf2, HO-1 and antioxidant protein in liver tissues were decreased, while the levels of oxidative stress and inflammation were increased. Compared with the CLP group, the levels of inflammatory factors and oxidative stress were significantly decreased in the CLP+SRT1720 group, the mRNA and protein expressions of SIRT1, Nrf2 and HO-1 were significantly increased [IL-6 (ng/L): 34.59±4.21 vs. 61.84±3.78, IL-1β (ng/L): 41.37±2.70 vs. 72.06±3.14, TNF-α (ng/L): 76.43±5.23 vs. 130.85±5.30, ALT (U/L): 30.71±3.63 vs. 64.23±4.59, AST (U/L): 94.57±6.08 vs. 145.15±6.86, MDA (μmol/g): 6.11±0.28 vs. 9.23±0.29, 8-OHdG (ng/L): 117.43±10.38 vs. 242.37±11.71, GSH (μmol/g): 11.93±0.88 vs. 7.66±0.47, SOD (kU/g): 121.58±5.05 vs. 83.57±4.84, SIRT1 mRNA (2-ΔΔCt): 1.20±0.13 vs. 0.46±0.02, Nrf2 mRNA (2-ΔΔCt): 1.21±0.12 vs. 0.58±0.03, HO-1 mRNA (2-ΔΔCt): 1.71±0.06 vs. 0.48±0.07, SIRT1 protein (SIRT1/β-actin): 0.89±0.04 vs. 0.58±0.03, Nrf2 protein (Nrf2/β-actin): 0.87±0.08 vs. 0.51±0.09, HO-1 protein (HO-1/β-actin): 0.93±0.14 vs. 0.54±0.12, all P < 0.05], these results indicated that SIRT1 agonist SRT1720 pretreatment could improve liver injury in sepsis rats. However, pretreatment with SIRT1 inhibitor EX527 showed the opposite effect [IL-6 (ng/L): 81.05±6.47 vs. 61.84±3.78, IL-1β (ng/L): 93.89±5.83 vs. 72.06±3.14, TNF-α (ng/L): 177.67±5.12 vs. 130.85±5.30, ALT (U/L): 89.33±9.52 vs. 64.23±4.59, AST (U/L): 179.59±6.44 vs. 145.15±6.86, MDA (μmol/g): 11.39±0.51 vs. 9.23±0.29, 8-OHdG (ng/L): 328.83±11.26 vs. 242.37±11.71, GSH (μmol/g): 5.07±0.34 vs. 7.66±0.47, SOD (kU/g): 59.37±4.28 vs. 83.57±4.84, SIRT1 mRNA (2-ΔΔCt): 0.34±0.03 vs. 0.46±0.02, Nrf2 mRNA (2-ΔΔCt): 0.46±0.04 vs. 0.58±0.03, HO-1 mRNA (2-ΔΔCt): 0.21±0.03 vs. 0.48±0.07, SIRT1 protein (SIRT1/β-actin): 0.47±0.04 vs. 0.58±0.03, Nrf2 protein (Nrf2/β-actin): 0.32±0.07 vs. 0.51±0.09, HO-1 protein (HO-1/β-actin): 0.19±0.09 vs. 0.54±0.12, all P < 0.05]. SIRT1 can inhibit the release of proinflammatory factors and alleviate the oxidative damage of hepatocytes by activating Nrf2/HO-1 signaling pathway, thus playing a protective role against CLP-induced liver injury.

Objective To investigate the effect and mechanism of gadolinium chloride alleviates partial warm ischemia-reperfusion injury of liver by suppressing kupffer cell function in mice. Methods Forty-eight male C57BL/6 mice were randomly divided into sham-operated group (Sham), Hepatic ischemia-reperfusion injury (HIRI) group, gdolinium chloride groups (Gd+ IRI), and cobalt protoporphyrin (CoPP+ IRI) group (n=12). The rats were injected with the same dose of normal saline in Sham group and IRI group. Gd+ IRI group were intraperitoneally injected with GdCl3 (20 mg/kg) 24 hours before operation. At the same time, CoPP+ IRI group were intraperitoneally injected with CoPP (5 mg/kg). Except for Sham group, an 70% volume HIRI model was established by means of 60 minutes ischemia and then 6 hours reperfusion in the other groups. The levels of serum aspartate transaminase (AST) and alanine aminotransferase (ALT) in each group were compared. Enzyme-linked immunosorbent assay were used to test the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the liver tissue. The level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, heme oxygenase-1 (HO-1), and protective factor IL-10 mRNA level were detected by real time quantitative polymerase Chain Reaction (RT-PCR). Immunohistochemical staining was used to measure Fas, FasL protein expression level of extrahepatic biliary epithelial cells. Results Respectively, the serum ALT level in the HIRI, Gd+ IRI and CoPP+ IRI groups was (1 236.7±62.4), (638.9±50.9), (740.3±53.1) U/L, and the AST level was (1 107.8±68.3), (568.5±42.7), (679.1±49.9) U/L, the serum level of ALT and AST in Gd+ IRI and CoPP+ IRI groups was lower than IRI group (t=6.721, P<0.01; t=4.732, P<0.05; t=5.984, P<0.01; t=2.691, P<0.05). Compared with IRI group, the activity of SOD and GSH-Px was promoted (t=7.301, P<0.01; t=1.937, P<0.05), whereas the levels of MDA was reduced (t=9.519, P<0.01; t=8.635, P<0.01). Simultaneously, the TNF-α, IL-1β and IL-6 mRNA level in Gd+ IRI and CoPP+ IRI groups were decreased (t=6.721, P<0.01; t=2.316, P<0.05), and the levels of IL-10 and HO-1 mRNA were increased (t=2.973, P<0.05; t=7.921, P<0.01). After hepatic artery reflow 6 h, the Fas expression levels on bile ducts epithelial cells in Gd+ IRI and CoPP+ IRI groups respectively was 22.4%, 29.7%, which was lower than IRI group (38.9%) (χ2=6.561, P<0.01; χ2=2.547, P<0.05). The FasL expression levels in Gd+ IRI and CoPP+ IRI groups respectively was 21.2%, 25.1%, which was lower than IRI group (36.5%) (χ2=5.982, P<0.05; χ2=3.188, P<0.05). Conclusion Gdolinium chloride shows an protective function aganist liver ischemia-reperfusion iniury in mice by Oxidative stress, inhibiting inflammation and cell apoptosis. The up-regulation of HO-1 by gdolinium chloride may be the possible mechanism. The up-regulation of HO-1 and inhibiting the Fas/FasL protein expression by gdolinium chloride may be the possible mechanism. Key words: Gdolinium chloride; Liver; Ischemia-reperfusion injury; Heme oxygenase-l

Background: Dental workers are exposed to elevated levels of elemental mercury vapor substantially above the occupational exposure standards when placing or removing mercury/silver tooth restorations and disposing of mercury waste. This results in a significant increase in occupational exposure and risk of mercury intoxication.Methods: To evaluate the occupational exposure of dental workers to amalgam in four dental clinics in Baghdad city, the concentrations of mercury vapor were measured seasonally from February to November 2016. Samples of blood and urine were collected from 30 dental workers (exposed individuals) and five non-occupationally exposed individuals. Biochemical parameters such as cholesterol, liver enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase), renal enzymes (urea and creatinine), total protein and reduced glutathione (GSH) were observed.Results: The results indicated that mercury vapor levels varied from 84.7 ± 18.67 to 609.3 ± 238.90 µg/m3 and most concentrations were above the occupational exposure standards. The results of the biochemical parameters showed a significant increase in levels of cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and no significant increase in blood urea and creatinine in dental workers in comparison with unexposed persons (control). Although the results showed a significant reduction in the levels of glutathione and total protein, there was no significant decrease in the levels of alkaline phosphatase (ALP) in exposed dental workers when compared with non-occupationally exposed individuals.Conclusions: It is concluded that mercury vapor concentrations in the indoor air of some dental clinics in Baghdad city are high and exceed the OSHA STEL(Occupational Safety and Health Administration Short Term Exposure Limit). The present data showed that altered biochemical parameters can be used as efficient bioindicators for mercury toxicity.

Objective To investigate the effects of pretreatment with etomidate on hepatic injury and the contents of alanine transaminase (ALT),aspartate transaminase (AST) in plasma and malondialdehyde (MDA),superoxide dismutase (SOD) in hepatic tissue during hepatic ischemia/repeffusion injury(HI/RI) in dogs.Methods 20 adult healthy hybrid canines were randomly divided into 4 groups(n=5): Sham group(group S),ischemia/reperfusion group (group I/R),low dosage of Etomidate group(group El,0.6 mg/kg) and high dosage of Etomidate group (group E2,1.5 mg/kg).Canines in all groups were injected Etomidate or NS except group S.The porta hepatis of canines in group S was separated without ligation.The model of HI/RI were established by ligating porta hepatis.The biochemical indicators of ALT and AST in plasma were measured at 4 time points: before blocked,30 min after ischemis,l,2 h after repeffusion.The contents of MDA and activity of SOD in hepatic tissue were also measured.Hepatic tissue was observed with light microscope after operation.Results Compared with group S,group I/R,group E1 and group E2 increased the level of ALT and AST in plasma (P＜0.01).Compared with group I/R,the level of ALT,AST in group E1 and group E2 decreased significantly(P＜0.01),moreover,group E2 decreased more obviously.Reperfusion 2 h: ALT: (2911±89) U/L(group I/R),(863±95) U/L(group E2); AST: (2722±103) U/L(group I/R),(1056±115) U/L(group E2)].Compared with group S,group I/R,group E1 and group E2 increased the level of MDA and group I/R decreased the expression level of SOD,group E1 and group E2 increased the level of SOD in hepatic tissue (P＜0.01).Compared with group I/R,group E1 and group E2 decreased significantly the level of MDA and increased significantly the level of SOD in hepatic tissue (P＜0.01),and group E2 more obviously[MDA:(21.70±-2.01) nmol·mg-1·prot-1 (group I/R),(12.69±1.02) nmol·mg-1·prot-1 (group E2),SOD: (191±12) nmol·mg-1 ·prot-1(group I/R),(634±26) nmol· mg-1·prot-1 (group E2)].Light microscope showed evidently that the pathological changes of hepatic tissue were more slight in group E1 and group E2 than that in group I/R,and group E2 more slight than group El.Conclusions Pretreatment with etomidate has protective effects on hepatic ischemia reperfusion injury,and it is related to the control lipid peroxidation of etomidate.And the protective effects of high dosage of etomidate (1.5 mg/kg) was more reliable. Key words: Etomidate ; Pretreatment ; Hepatic ischemia/reperfusion ; Alanine transaminase ; Aspartate transaminase; Malondialdehyde; Superoxide dismutase

Objective To investigate the effect and mechanism of irisin postconditioning on hepatic ischemia reperfusion injury in rats. Methods Totally 36 SD rats were randomly divided into sham group (S), model group (I/R) and irisin group (Ir), with 12 rats in each group. Hepatic ischemia was constructed in model group and irisin group by ligating left middle lobe of liver vascular branches for 60 min. Irisin was administered at the beginning of reperfusion by intravenous injection at the concentration of 10 μg/kg for rats in irisin group. We only dissected the hepatic duodenal ligament of rats in the S group. Serum and liver tissues were collected at 6 h after reperfusion through the inferior chamber. The serum levels of alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), interleukin (IL)-6, IL-1βand tumor necrosis factor-α (TNF-α) were examined. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in liver tissue were measured. The pathological changes of liver tissue were observed by hematoxylin and eosin (HE) staining. The phosphorylations of janus kinase 2 (JAK2), signal transducer and activators of transcription 3 (STAT3) and B cell lymphoma/leukemia-2 (bcl-2), bcl-2 associated X protein (bax), cysteinyl aspartate-specific protease (Caspase)-3 were assessed by Western blotting. Results The ALT levels in S group, I/R group and irisin group were as follows: (75.24±2.65), (705.33±4.02), (385.46±3.58) U/L; The AST levels were as follows: (122.33±6.76), (1 357.54±5.23), (738.26±3.98) U/L; The IL-6 levels were as follows: (104±16), (586±86), (275±35) ng/L; The TNF-α levels were as follows: (92±10), (1 165±102), (511±73) ng/L; The IL-1β levels were as follows: (98±12), (610±79), (312±41) ng/L; The MDA contents were as follows: (174±38), (1 900±460), (1 055±266) ng/L; The SOD contents were as follows: (124±10), (46±8), (70±10) ng/L; The GPX contents were as follows: (106±12), (42±5), (62±11) ng/L; The Caspase-3 levels were as follows: (0.22±0.06), (0.86±0.14), (0.57±0.11) ng/L; The p-JAK2 levels were as follows: 0.44±0.05, 0.91±0.07, 0.62±0.11; The p-STAT3 levels were as follows: 0.35±0.04, 0.86±0.08, 0.57±0.07. As compared with the sham group, the levels of ALT, AST, IL-6, TNF-α, IL-1β, MDA and Caspase-3 were significantly increased (t=445.551, 219.362, 21.700, 7.700, 36.182, 14.132, 24.191, 10.111, 13.753, 7.023, 14.456 and 6.556, P<0.01). The activities of GPX and SOD in model group and irisin group were significantly decreased (t=20.374, 14.104, 15.945 and 10.965, P<0.01), and the pathological damage worsened and the expression levels of activated p-JAK2 and p-STAT3were up-regulated in other groups (t=14.289, 5.479, 19.054 and 8.224, P<0.01); As compared with model group, the levels of ALT, AST, IL-6, TNF-α, IL-1β, MDA and Caspase-3 in irisin group were significantly decreased (t=226.183, 14.000, 14.081, 22.052 and 7.906, P<0.01), and pathological damage was alleviated and the expression levels of activated SOD and GPX significantly increased (t=6.274 and 4.985, P<0.01). The p-JAK2 and p-STAT3 were down-regulated in irisin group (t=8.819 and 10.834, P<0.01). Conclusion Exogenous irisin postconditioning can significantly decrease hepatic ischemia-reperfusion injury in rats by suppressing oxidative stress and cell apoptosis, and the mechanism may be associated with the suppression of JAK2/STAT3 signaling activation. Key words: Irisin; Hepatic ischemia; Reperfusion injury; Janus kinase 2; Signal transducer and activators of transcription 3

Hepatoprotective action of papain-hydrolyzed buffalo milk protein on carbon tetrachloride oxidative stressed albino rats

To investigate the relationship between plasma oxidative stress factors levels and organ damage parameters as well as prognosis in patients with sepsis. A case-control study was conducted. Twenty-five patients admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from March to December in 2016 and diagnosed as sepsis were enrolled as study subjects. Another 15 patients without sepsis admitted to surgical ICU in the same period were enrolled as controls. General demographic data, main diagnoses, acute physiology and chronic health evaluation II (APACHE II) score within 24 hours, clinical laboratory indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (SCr), blood urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT), white blood count (WBC)] and oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO)] as well as length of ICU stay, total hospital stay and 28-day mortality were recorded. Spearman or Pearson correlation method was used to analyze the correlation between oxidative stress indicators and organ damage indicators as well as prognosis in patients with sepsis. Receiver operator characteristic (ROC) curve was plotted to evaluate the predictive value of oxidative stress indicators for 28-day mortality in patients with sepsis. The length of ICU stay in sepsis group was significantly longer than that in non-sepsis group [days: 7.0 (5.5, 11.0) vs. 4.0 (1.0, 11.0), P < 0.05], and AST, BUN, CRP, PCT, plasma MDA and NO levels were significantly higher than those in non-sepsis group [AST (U/L): 50.76±19.53 vs. 28.53±14.02, BUN (mmol/L): 9.99±5.26 vs. 6.97±4.32, CRP (mg/L): 109.28±42.79 vs. 60.33±46.68, PCT (μg/L): 5.4 (0.3, 24.0) vs. 0.6 (0.1, 1.5), MDA (ng/L): 488.31±76.68 vs. 399.30±50.23, NO (ng/L): 5.08±0.89 vs. 4.42±0.88, all P < 0.05]. There was no significant difference in gender, age, APACHE II score, total hospital stay, 28-day mortality, ALT, SCr, WBC or plasma SOD activity between the two groups. The correlation analysis between oxidative stress parameters and organ damage parameters as well as prognosis in patients with sepsis showed that MDA and NO were positively correlated with SCr (r value was 0.426 and 0.431, respectively, both P < 0.05), and there was a positive correlation between MDA and NO (r = 0.990, P < 0.01); plasma SOD activity was negatively correlated with 28-day mortality (r = -0.468, P < 0.05), while MDA and NO levels were positively correlated with 28-day mortality (r value was 0.598 and 0.611, respectively, both P < 0.01). ROC curve analysis showed that plasma SOD, MDA and NO levels had a good independent predictive effect on 28-day mortality, the area under ROC curve (AUC) was 0.816±0.087, 0.904±0.078 and 0.912±0.071, and the best cut-off value was 40.76% (sensitivity 68.4%, specificity 100%), 487.93 ng/L (sensitivity 83.3%, specificity 89.5%) and 5.31 ng/L (sensitivity 83.3%, specificity 89.5%), respectively. The plasma levels of oxidative stress factors in patients with sepsis are significantly increased, which is closely related to organ damage and poor prognosis. The plasma SOD, MDA and NO levels can be used as independent bio-marker to predict the 28-day mortality of patients with sepsis.

Organophosphorous pesticides, commonly used in agriculture for achieving better‐quality products, are toxic substances that have harmful effects on human health. Recent research on pesticides, especially pesticide mixtures, has shown that they are one of the key environmental health issues. The aim of the present study was to investigate the protective effects of Alstonia boonei ethanolic extract in dichlorvos‐induced neurotoxicity in Wistar rats. Dichlorvos (50 mg/kg body weight) was orally administered in Wistar rats for 14 days followed by the treatment of Alstonia boonei (200 and 400 mg/kg body weight) for 14 days. The activities of lipid peroxidation (LPO), reduced glutathione (GSH) and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level were measured to evaluate the toxicity of these pesticides in the brain. Histological examinations of the brain were monitored. Under the influence of dichlorvos, there was significant decrease in the activities of SOD, CAT, GPx, GSH, ALT and AST and significant increase in malondialdehyde. Alstonia boonei showed a significant brain‐protective effect by decreasing the level of lipid peroxidation and elevating the activities of antioxidative enzymes and the level of GSH. Furthermore, histological alterations in the brain were observed in dichlorvos‐untreated rats and were ameliorated in dichlorvos‐induced treated rats with Alstonia boonei. The observations presented lead us to conclude the harmful effects of dichlorovos during the exposure and the protective role of Alstonia boonei in minimizing these effects. Key words: Alstonia boonei, brain, dichlorvos, lipid peroxidation, organophosphate, oxidative stress, reactive oxygen species

To investigate the impact of autophagy on cardiac tissue injury following common bile duct ligation (CBDL) in rats. Twenty-four SPF grade healthy adult male Sprague-Dawley (SD) rats were randomly divided into four groups, with 6 rats in each group. The sham-operated (Sham) group underwent only dissection of the common bile duct without ligation. The CBDL group underwent CBDL to simulate jaundice-induced myocardial injury. The autophagy inhibitor 3-methyladenine (3-MA)+CBDL group was intraperitoneally injected with 15 mg/kg 3-MA 2 hours before modeling, and then injected once every other day. The CBDL+autophagy enhancer rapamycin (Rapa) group was intraperitoneally injected with Rapa 1 mg/kg 0.5 hour after modeling, and then injected once every other day. The rats in each group were sacrificed 2 weeks after surgery, and blood was taken from the inferior vena cava. Serum total bilirubin (TBil), alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) were detected by using a fully automated animal biochemical analyzer. Serum oxidative stress marker superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by colorimetric assay. The heart tissues of rats were taken and pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining. Transmission electron microscope was used to observe autophagosomes after double staining with uranyl acetate and lead citrate. The expressions of autophagy-related proteins were detected using Western blotting. Compared with the Sham group, the serum SOD activity of rats in the CBDL group was significantly decreased, while the serum MDA, TBil, ALT, AST, LDH, and CK-MB were significantly increased; the expressions of autophagy-related proteins Beclin-1 and microtubule-associated protein 1 light chain 3-II/I (LC3-II/I) were significantly increased, and p62 protein expression was significantly decreased. Autophagosomes were seen under electron microscopy in the CBDL group, and cardiac histopathological morphology showed focal necrosis in the myocardium as well as infiltration of inflammatory cells, dilatation of small interstitial blood vessels, and myocardial fiber degeneration. Compared with the CBDL group, cardiac tissue injury in rats was attenuated by pretreatment with the autophagy inhibitor 3-MA, with a decrease in inflammatory cell infiltration in myocardial tissue, a reduction in interstitial vasodilatation, and a decrease in the area of myocardial fibrosis; a decrease in the number of autophagosomes by electron microscopy; and a further rise in the viability of serum TBil, ALT, and AST [TBil (μmol/L): 184.40±6.74 vs. 120.70±16.93, ALT (U/L): 501.10±62.18 vs. 178.80±22.30, AST (U/L): 806.50±76.92 vs. 275.50±55.81, all P < 0.01], as well as a decrease in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 85.00±5.29 vs. 107.50±7.86, MDA (μmol/L): 10.72±0.93 vs. 15.06±1.88, LDH (U/L): 387.40±119.50 vs. 831.30±84.35, CK-MB (U/L): 320.10±14.04 vs. 814.70±75.66, all P < 0.05]. The expressions of the autophagy-related proteins Beclin-1 and LC3-II/I in cardiac tissues were significantly decreased [Beclin-1 protein (Beclin-1/GAPDH): 0.67±0.04 vs. 0.89±0.01, LC3-II/I ratio: 0.93±0.03 vs. 1.09±0.01, both P < 0.01], and p62 protein expression was significantly increased (p62/GAPDH: 0.99±0.01 vs. 0.60±0.01, P < 0.01). In contrast, compared with the CBDL group, after administration of the autophagy enhancer Rapa, the rats showed increased cardiac tissue injury, increased inflammatory cell infiltration in myocardial tissues, increased interstitial vasodilatation, and increased area of myocardial fibrosis; an increase in autophagosomes was seen by electron microscopy; the change tendency of serum biochemical indicators and proteins in myocardial tissues were opposite with autophagy inhibition group with a decrease in serum TBil, ALT, and AST [TBil (μmol/L): 22.00±3.21 vs. 120.70±16.93, ALT (U/L): 72.13±5.97 vs. 178.80±22.30, AST (U/L): 135.20±12.95 vs. 275.50±55.81, all P < 0.05], as well as a increase in the levels of serum SOD, MDA, LDH, and CK-MB [SOD (kU/L): 208.00±2.65 vs. 107.50±7.86, MDA (μmol/L): 20.38±0.40 vs. 15.06±1.88, LDH (U/L): 1 268.00±210.90 vs. 831.30±84.35, CK-MB (U/L): 1 150.00±158.70 vs. 814.70±75.66, all P < 0.05]. The protein expressions of Beclin-1 and LC3-II/I in cardiac tissues were significantly increased [Beclin-1 protein (Beclin-1/GAPDH): 0.96±0.01 vs. 0.89±0.01, LC3-II/I ratio: 1.19±0.01 vs. 1.09±0.01, both P < 0.05], and p62 protein expression was significantly decreased (p62/GAPDH: 0.19±0.02 vs. 0.60±0.01, P < 0.01). Activation of autophagy in CBDL rats led to myocardial tissue injury and reduced cardiac function. Inhibition of autophagy improved cardiac tissue injury in CBDL rats, while increasing autophagy exacerbated myocardial tissue injury.

Perchloroethylene (PCE) is the main solvent used in the dry cleaning industry worldwide. The aim of the present work was to evaluate the genotoxic potential of occupational exposure to PCE in dry cleaning workers. The study was carried out in 59 volunteers (30 workers, 29 controls). The genotoxic effect was evaluated by analyzing chromosome aberrations (CAs), and micronuclei (MN) and DNA damage (assessed by the comet assay) in peripheral blood lymphocytes. Environmental monitoring of exposure was carried out on personal breathing zone air samples collected during two consecutive working days by measuring the concentration of PCE air levels. The mean PCE concentration in workplace air of dry cleaning workers was 31.40 mg/m3. There were no significant differences in CA frequency between dry cleaning workers and the controls, but analysis showed a significant association of CA frequency with employment duration and frequency of exposure to PCE. The MN frequency and DNA damage detected by alkaline comet assay were significantly increased in dry cleaning workers compared to the controls. The results suggest that (a) chronic occupational exposure to dry cleaning solvents below permissible occupational exposure limit of 70 mg/m3 (i.e., ∼10.3 ppm) may lead to an increased risk of genetic damage among dry cleaning workers, and (b) CA, MN tests, and comet assay are useful to monitor populations exposed to low doses of PCE.

The aim of this study was to evaluate the oxidative status in ketotic cows. We observed changes in the oxidative status and correlations between the oxidative and metabolic status in non-ketotic (n=10), subclinical ketotic (n=10) and ketotic cows (n=10). Plasma samples were analysed by standard biochemical techniques and ELISA to determine traditional metabolic parameters: triglyceride (TG), phosphonium (P), calcium (Ca), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), immune globulin (Ig), total cholesterol (TC), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) and lactate dehydrogenase (LDH); energy metabolism indices: glucose, β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA); and indices of oxidative status: malondialdehyde (MDA), hydrogen peroxide (H2 O2 ), vitamin C, vitamin E, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), xanthine oxidase (XOD) and total antioxidant capacity (TAOC). The results of this study showed that plasma glucose levels were lower in ketotic and subclinical ketotic cows than in non-ketotic cows; however, the plasma NEFA and BHBA concentrations were higher. In addition, significant decreases in TC, HDL and VLDL and significant increases in AST, ALT and LDH were observed in the plasma of the ketotic cows. The ketotic cows showed decreased plasma SOD, CAT, vitamin C and vitamin E, inhibited hydroxyl radical capacity and increased plasma H2 O2 and MDA. There were positive correlations between the plasma NEFA and ALT, AST, LDH and MDA and negative correlations between the plasma NEFA and TC, HDL, VLDL, SOD, vitamin C, vitamin E, 1542280 uric acid and inhibited hydroxyl radical capacity. In addition, there were positive correlations between BHBA concentrations and ALT, AST and LDH and negative correlations between plasma BHBA concentrations and TC, HDL, VLDL, vitamin E and inhibited hydroxyl radical capacity. Overall, ketotic dairy cows experience oxidative stress, which is presumably associated with hyperketonemia and higher NEFA.