Superoxide Dismutase In Liver Tissue Research Articles

Protective effect of astaxanthin on acute liver injury induced by α-amanitin in mice

Objective: To explore the protective effect of astaxanthin on acute liver injury induced by α-amanitin in mice. Methods: In June 2023, 42 healthy SPF male Kunming mice were selected. The mice were divided into blank control group, model (0.45 mg/kg α-amanitin) group, olive oil (10 ml/kg olive oil) group, low dose (20 mg/kg) astaxanthin group, medium dose (40 mg/kg) astaxanthin group, high dose (80 mg/kg) astaxanthin group and silybin (20 mg/kg) group by random number table method. Each group had 6 animals. Mice in the blank control group were intraperitoneally injected with 10 ml/kg normal saline, and mice in the other group were injected with α-amanitin. After that, the blank control group and model group were infused with 10 ml/kg normal saline, olive oil group and astaxanthin groups were given olive oil and astaxanthin according to dose by gavage, and silybin group was injected with silybin by dose. The drug was administered once every 12 h for a total of 4 doses. After 60 h, the mice were killed, the liver weight was weighed, and the liver index was calculated. The contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of mice were detected, and the contents of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA) in liver tissues were also detected. One-way analysis of variance (ANOVA) was used to compare the difference of indexes among each group, and pairwise comparison was performed by Dunnett-t test. Results: The mice in the blank control group had smooth hair color, good spirit and normal behavior, while the mice in the other groups showed varying degrees of retardation and decreased diet, and no death occurred in each group. Body mass[ (26.67±1.51) g] and liver mass[ (1.23±0.14) g] in model group were significantly lower than those in blank control group [ (33.50±2.43) g and (1.87±0.16) g], and the differences were statistically significant (P<0.05). The liver index [ (5.39±0.32) %, (5.83±0.30) %, (5.75±0.24) % and (5.78±0.16) %] in low, medium and high dose astaxanthin groups and silybin group were significantly higher than those in model group [ (4.61±0.12) %], and the differences were statistically significant (P<0.05). Serum ALT and AST contents in model group [ (153.04±13.96) U/L and (59.08±4.03) U/L] were significantly higher than those in blank control group [ (13.77±1.29) U/L and (10.21±0.35) U/L], and the differences were statistically significant (P<0.05). The contents of CAT, GSH and SOD in liver tissues of model group [ (9.40±2.23) U/mgprot, (3.09±0.26) μmol/gprot and (48.94±3.13) U/mgprot] were significantly lower than those of blank control group [ (26.36±2.92) U/mgprot, (6.76±0.71) μmol/gprot and (89.89±4.17) U/mgprot], the differences were statistically significant (P<0.05). MDA content[ (6.33±0.24) nmol/mgprot] in liver tissue of model group was significantly higher than that of blank control group [ (0.91±0.21) nmol/mgprot], and the difference was statistically significant (P<0.05). The CAT contents[ (18.64±1.76) U/mgprot, (18.20±1.76) U/mgprot, and (15.54±1.36) U/mgprot] in liver tissues of low, medium and high dose astaxanthin groups were significantly higher than those of model group, with statistical significances (P<0.05). Compared with model group, SOD contents[ (72.16±7.44) U/mgprot, (93.18±5.28) U/mgprot, (103.78±7.07) U/mgprot, and (96.60±7.02) U/mgprot] in liver tissues of mice in low, medium and high dose astaxanthin groups and silybin group were significantly increased (P<0.05), MDA contents [ (4.30±0.84) U/mgprot, (3.66±0.28) U/mgprot, (2.96±0.29) U/mgprot, and (2.88±0.39) U/mgprot] were significantly decreased (P<0.05). Compared with model group, GSH content [ (7.90±1.25) μmol/gprot] in high dose astaxanthin group was significantly increased (P<0.05) . Conclusion: Astaxanthin may alleviate acute liver injury induced by α-amanitin by alleviating oxidative stress in mice liver.

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2mL/day sc. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; H-homocysteine 0.45µmol/g b.w. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; CPA-saline 0.2mL/day sc. 2×/day for 14days + aerobic treadmill training for 28days; and HPA-homocysteine 0.45µmol/gb.w. 2×/day for 14days + aerobic treadmill training for 28days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Protective effect and mechanism of quercetin on acute liver injury induced by diquat poisoning in mice

To investigate the protective effect of quercetin (QR) on acute liver injury induced by diquat (DQ) poisoning in mice and its mechanism. Eighty healthy male C57BL/6 mice with SPF grade were randomly divided into control group, DQ model group, QR treatment group, and QR control group, with 20 mice in each group. The DQ poisoning model was established by a one-time intraperitoneal injection of DQ solution (40 mg/kg); the control and QR control groups received equivalent amounts of distilled water through intraperitoneal injection. Four hours after modeling, the QR treatment group and the QR control group received 0.5 mL QR solution (50 mg/kg) through gavage. Meanwhile, an equivalent amount of distilled water was given orally to the control group and the DQ model group. The treatments above were administered once daily for seven consecutive days. Afterwards, the mice were anesthetized, blood and liver tissues were collected for following tests: changes in the structure of mice liver tissue were observed using transmission electron microscopy; the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected using enzyme linked immunosorbent assay (ELISA); the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) in liver tissues were measured using the water-soluble tetrazolium-1 (WST-1) method, the thiobarbituric acid (TBA) method, and enzymatic methods, respectively; the protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues were detected using Western blotting. Severe mitochondrial damage was observed in the liver tissues of mice in the DQ model group using transmission electron microscopy, yet mitochondrial damage in the QR treatment group showed significant alleviation. Compared to the control group, the DQ model group had significantly increased levels of MDA in liver tissue, serum AST, and ALT, yet had significantly decreased levels of GSH and SOD in liver tissue. In comparison to the DQ model group, the QR treatment group exhibited significant reductions in serum levels of ALT and AST, as well as MDA levels in liver tissue [ALT (U/L): 52.60±6.44 vs. 95.70±8.00, AST (U/L): 170.45±19.33 vs. 251.10±13.09, MDA (nmol/mg): 12.63±3.41 vs. 18.04±3.72], and notable increases in GSH and SOD levels in liver tissue [GSH (μmol/mg): 39.49±6.33 vs. 20.26±3.96, SOD (U/mg): 121.40±11.75 vs. 81.67±10.01], all the differences were statistically significant (all P < 0.01). Western blotting results indicated that the protein expressions of Nrf2 and HO-1 in liver tissues of the DQ model group were significantly decreased compared to the control group. On the other hand, the protein expressions of Keap1 and activated caspase-9 were conspicuously higher when compared to the control group. In comparison to the DQ model group, the QR treatment group showed a significant increase in the protein expressions of Nrf2 and HO-1 in liver tissues (Nrf2/β-actin: 1.17±0.08 vs. 0.92±0.45, HO-1/β-actin: 1.53±0.17 vs. 0.84±0.09). By contrast, there was a notable decrease in the protein expressions of Keap1 and activated caspase-9 (Keap1/β-actin: 0.48±0.06 vs. 1.22±0.09, activated caspase-9/β-actin: 1.17±0.12 vs. 1.59±0.30), the differences were statistically significant (all P < 0.01). QR may reduce acute liver injury induced by DQ poisoning in mice via activating Keap1/Nrf2 signaling pathway.

Diabetes-correcting and antioxidant effects of grape pomace extract rich in natural complex of polyphenols

Background. The positive health effects of polyphenols have led to an increased scientific interest in these natural compounds over the past decade. Many studies confirm the effectiveness of polyphenols as additional therapy in diabetes, especially due to the sugar-lowering effect of polyphenols. The aim of the research was to investigate the morphological and functional state of peripheral blood erythrocytes and the indices of oxidative stress in the liver of rats with experimental diabetes and after the administration of grape pomace extract rich in natural complex of polyphenols. Materials and Methods. We obtained grape pomace extract, which contains a variety of polyphenolic compounds. Rats of the following groups were used in the experiments: control animals, animals treated with grape pomace extract rich in natural complex of polyphenols for 14 days, animals with streptozotocin-induced diabetes mellitus, and animals with streptozotocin-induced diabetes mellitus treated with grape pomace extract rich in natural complex of polyphenols for 14 days. The number of erythrocytes and reticulocytes, the concentration of hemoglobin and glycated hemoglobin were determined in the peripheral blood of rats. The activities of catalase, superoxide dismutase and the content of thiobarbituric acid-reactive substance and carbonyl groups of proteins were determined in the liver tissues of rats. Results. The study has shown an increase in the number of erythrocytes and the level of hemoglobin, a decrease in the level of glycated hemoglobin and the number of reticulocytes in the peripheral blood of rats after administration of grape pomace extract rich in natural complex of polyphenols to rats with experimental diabetes. A decrease in the content of thiobarbituric acid-reactive substance and the content of carbonyl groups of proteins of neutral and basic character and an increase in the activity of catalase and superoxide dismutase in liver tissues were found under the same conditions. Conclusions. The results indicate that the extract of the natural complex of polyphenols is capable of correcting the morphological and functional state of erythrocytes, as well as improving the activity of antioxidant enzymes and the content of marker molecules of oxidative stress in hepatocytes of rats under experimental diabetes mellitus.

Investigation of the protective effect of Tarantula cubensis extract on the liver and brain of rats exposed to gentamicin

This study aimed to investigate the possible protective effects ofTarantula cubensisextract (TCE) on the liver and brain of rats exposed to gentamicin (GM). A total of 40 male Sprague Dawley rats were randomly divided into four equal groups: control, TCE, GM, and GM+TCE. Some biochemical indices, apoptotic markers (B-cell lymphoma 2 [Bcl-2] and Bcl-2 associated X protein [Bax]) and histopathological changes were evaluated. In the GM group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, brain and liver tissue malondialdehyde (MDA) concentrations increased; albumin, total protein, brain and liver tissue superoxide dismutase (SOD) concentrations and the total antioxidant status (TAS) decreased. Apoptosis induced down-regulation of Bcl-2 and up-regulation of Bax in liver and brain tissues in the GM group. GM-treated animals demonstrated several histopathological changes. TCE administration restored some histopathological changes. Lipid peroxidation and apoptosis decreased, antioxidant defense increased, concentrations of some serum biochemical indices (AST, ALT, ALP, GGT, and total bilirubin) decreased, and albumin and total protein levels increased in the TCE+GM group compared to the GM group. In conclusion, high doses of GM induce adverse effects on liver and brain tissue of rats. It was concluded that TCE administration can improve these adverse effects by reducing lipid peroxidation and apoptosis, improving the antioxidant defense system. TCE can be used to protect against the toxic effect of GM and other chemical agents in the liver and brain in veterinary medicine. However, additional studies are needed to confirm this assumption.

PS-B07-10: SUPEROXIDE DISMUTASE PROFILE OF LIVER TISSUE IN HYPERURICEMIA RATS AFTER DAILY CONSUMPTION OF COFFEE

Background: The elevation of serum uric acid may cause metabolic syndrome and increase systemic inflammation also oxidative stress which are the risk factors for liver disease. Recently, coffee as the most popular drink worldwide could promote antioxidant activity due to some anti-inflammatory effects of some polyphenolic compounds such as cafestol, kahweol, and diterpenes. This study aimed to analyze the profile of liver tissue superoxide dismutase (SOD) in hyperuricemia rats after daily consumption of coffee. Method: Four groups, each consisting of 6 rats (Rattus norvegicus), respectively were observed as 1) negative control group; 2) positive control group; 3) caffeinated coffee group; 4) decaffeinated coffee group. Hyperuricemia was conditioned by administering high purine intake into the 2nd until 4th group as much as 140 mg/200gr of weight. Coffee, which is caffeinated and decaffeinated was given to the third and the fourth group respectively with doses 144 mg/200gr of weight. SOD of liver tissue was measured after 30 days of treatment. Result: In hyperuricemia rats, daily consumption of coffee shows higher liver SOD levels compared to a positive control group. The average (+SD) of liver SOD each group respectively 79.51(+3.06); 32.24(+3.53); 53.28(+4.49); and 68.03(+4.72). Numeric comparative hypothetic test using one-way ANOVA shows the difference mean between each group was statistically significant (95%CI; p &lt; 0.05). Conclusion: Daily consumption of both caffeinated and decaffeinated coffee may reduce oxidative stress in liver tissue of hyperuricemia rats.

The Effect of Rectal Ozone Use on Bacterial Translocation and Oxidative Stress in Experimental Colitis Model

Objective: The aim of this study was to examine the effect of rectal ozone on the histopathological healing of the colonic mucosa, tissue oxidative stress, and bacterial translocation in the experimental colitis model. Materials and Methods: Three groups of rats were randomly formed [Group 1: Sham group, group 2: Control group, group 3: Ozone treatment group]. Microscopic and macroscopic scoring were done histopathologically in all groups. Glutathione-s-transferase (GST), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels were measured in the colon and liver tissue. Blood cultures were taken for the detection of bacterial translocation. Results: Microscopic damage scores were found as 0.0 (0.0-2.0) in the sham group, 3.0 (3.0-3.0) in the control group, 2.0 (0.0-2.0) in the ozone treatment group (p=0.001). Macroscopic damage scores were found as 0.0 (0.0-1.0) in the sham group, 3.0 (0.0-4.0) in the control group, 0.0 (0.0-1.0) in the ozone treatment group; the scores of ozone treatment and sham groups were found to be statistically different (p=0.004). Compared to the control group, the bacterial translocation in the liver, mesenteric lymph node, portal vein, spleen, and systemic blood was fewer in the ozone treatment group. Statistically significant differences were also observed between the groups’ SOD and GST levels in colon tissue and MDA, SOD, and GST levels in liver tissue. Regarding MDA values in the liver tissue of the groups, it was 1.95±0.43 in Group I, 3.63±0.81 in Group II, and 1.19±0.72 U/mg in Group III (p=0.017). When the liver tissue SOD levels of the groups were examined, it was 8.21±0.76 U/mg in Group I, 4.57±0.58 U/mg in Group II, and 8.62±1.13 U/mg in Group III (p=0.029). When GST values in liver tissue belonging to the groups were examined, 0.35±0.16 in Group 1, 0.23±0.03 in Group II, 0.49±0.13 U/mg in Group III (p=0.036). Conclusion: Rectal ozone application plays a role in increasing the organism’s antioxidant activity and has an effective role in increasing the enzyme activities of antioxidant defenses. In addition, rectal ozone application has a positive effect on wound healing at a histopathological level and reduces bacterial translocation in various tissues.

The healing effects of Ganoderma lucidum on intestinal ischemia-reperfusion damage in rats

Background/Aim: Intestinal ischemia-reperfusion (I/R) injury causes serious clinical problems and carries high morbidity and mortality risks. Ganoderma lucidum (GL) is known as an anti-inflammatory immunomodulator and antioxidant. This study aimed to investigate the curative effects of GL on intestinal I/R injury in rats. Methods: Twenty-four Wistar-Albino male rats were randomly divided into three groups. After 30/90 minutes of I/R, intestinal and hepatic tissue examples were histologically examined. Biochemical analysis, serum, intestinal and hepatic tissue malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were measured. Results: The I/R group had significantly elevated leukocyte, thrombocyte, serum, and intestinal and hepatic tissue MDA levels compared to the sham group (P < 0.05). Serum, intestinal tissue, and liver tissue SOD levels were significantly lower in the I/R group than in the control group (P < 0.05). In addition, GSH-Px levels measured in serum and liver tissue were lower in the I/R group. However, the use of GL prevented these decreases due to I/R damage. Prior administration of GL considerably alleviated histopathologic changes due to I/R injury in the intestinal and liver tissue samples. Conclusions: Our experimental study showed that I/R injury led to significant oxidative stress by inducing free oxygen radicals in intestinal and hepatic tissues. Serum and tissue MDA, SOD, and GSH-Px levels were considerably useful laboratory parameters in identifying oxidative stress. The protective effects of GL on intestinal I/R injury were promising considering these parameters.

Preparation of long-acting microspheres loaded with octreotide for the treatment of portal hypertensive

The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the general properties of microspheres to reduce burst release and enable them to be used for portal hypertension. Octreotide microspheres were prepared by modified double emulsion solution evaporation method after optimizing preparation conditions. The results showed that Octreotide microspheres had a particle size of 57.48 ± 15.24 μm, and the initial release was significantly reduced. In vitro release and in vivo pharmacokinetic data indicated that Octreotide was released stably within 1200 h. The effects on portal vein pressure, liver tissue morphology and other related indexes were observed after administration. As obvious results, injection of Octreotide microspheres could significantly reduce portal vein pressure and reduce the portal vein lumen area in experimental cirrhotic portal hypertensive rats. The optimized Octreotide PLGA microsphere preparation has been proved to have a good effect on PHT in vivo after detecting aminotransferase (AST) and alanine aminotransferase (ALT) activity, liver tissue hydroxyproline (Hyp) content, serum and liver tissue malondialdehyde (MDA) levels, plasma prostacyclin (PGI2) levels, and liver tissue tumor necrosis factor (TNFα) content. In addition, serum and liver tissue superoxide dismutase (SOD) activity and liver tissue glutathione (GSH) content, plasma thromboxane (TXA2), serum nitric oxide (NO), liver tissue nitric oxide synthase (NOS), and plasma and liver tissue endothelin (ET) were significantly increased.

Effect of electroacupuncture on liver surface blood perfusion and related indexes of oxidative stress in mice with acute alcoholic liver injury

To observe the effect of electroacupuncture (EA) on liver surface blood perfusion and related indexes of oxidative stress in mice with acute alcoholic liver injury （AALI）, so as to explore its mechanism underlying improving of AALI. Twenty-four Kunming mice were randomly divided into control, model and EA groups (8 mice/group). AALI model was established by intragastric administration of 50% ethanol at 6 g/kg. EA (4-6 V, 50 Hz) was applied to bilateral"Zusanli"(ST36) and"Taichong"(LR3) for 30 min. The liver surface blood perfusion was dynamically observed by moorFLPI laser speckle imager for 30 min. The morphological changes of the liver tissue were determined by H.E. staining. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver were measured by ELISA. Compared with the control group, the model group had markedly pathological changes of the hepatic cords, hepatic sinuses and hepatocytes shown by H.E. staining, a significant reduction in liver surface blood perfusion and the content of SOD in liver tissue (P<0.01, P<0.05), and a significant increase in the content of MDA in liver tissue (P<0.05). Compared with the model group, H.E. staining showed reduced pathological changes of the liver tissue, meanwhile the liver surface blood perfusion significant increased (P<0.05) and the content of MDA in liver tissue significantly decreased (P<0.01) in the EA group. EA can improve the liver surface circulation of AALI mice, and regulate the oxidative stress response, and thus help to repair the damage of liver tissue.

Hepatoprotective effects and mechanisms of Ixeris denticulate water extract on liver cirrhosis in experimental rat

BackgroundTo explore the protective effect and mechanisms of Ixeris denticulate water extract (IDWE) in the development of liver cirrhosis in experimental rat.MethodsSixty rats were randomly divided into five groups: control group, model group and IDWE (2, 4 and 8 g/kg) treatment groups. Alanine transferase (ALT), aspartate transaminase (AST), albumin (ALB), tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6 and IL-8 in serum and superoxide dismutase (SOD), malondialdehyde (MDA) in liver tissue were evaluated, respectively. The liver index, liver morphology and liver histopathological analysis were detected as a supportive data. The liver protein expression of Bcl-2 and Bax were assessed by western blot, and NF-κB p65 protein expression was determined by immunohistochemistry analysis.ResultsThe result showed that a significantly decrease in the levels of serum AST, ALT and serum inflammatory factors TNF-α, IL-6 and IL-8 in IDWE-treated rats. The levels of serum ALB and SOD in liver tissue were markedly increased after IDWE treated, compared with model rats. Furthermore, IDWE-treated group also exhibited a down-regulated protein expression of NF-κB p65 and Bax, up-regulated Bcl-2 protein expression.ConclusionsIDWE could effectively alleviate the course of liver cirrhosis in rat model, which may be a potent hepatoprotective agent in clinical therapy in the future.

Effects of ginger along with exercise training on serum levels of ALT and AST liver enzymes and malondialdehyde and the activity of liver tissue superoxide dismutase in male Wistar rats

Background and aims: The purpose of this study was to examine the effect of 2 months of endurance training (ET) along with ginger consumption on the serum levels of liver enzymes (ALT and AST), enzymatic activity of superoxide dismutase, and malondialdehyde (MDA) in liver tissue in male Wistar rats. Material and Methods: 40 adult male Wistar rats were randomly divided into 5 groups according to the weight as follows: control (n=8), sham (n=8), ET (n=8), ginger (n=8), and ET + ginger (n=8). The training protocol was an ET program on a treadmill for two months (5 days a week). Besides standard water and food, in groups using the supplement, 100 mg of ginger solution per kg body weight of the rats was injected three days a week. Then, 48 hours after the last training session and after 8 hours of fasting, blood and tissue samples were collected over night and the serum levels of liver enzymes (ALT and AST), MDA level of the liver tissue, and activity of the liver superoxide dismutase (SOD) were measured. One-way ANOVA and Tukey post-hoc test were used for data analysis. Results: The results showed that after 8 weeks, the activity of liver SOD in ET group (131.7±18.6, P=0.001) and ET + Ginger group (130.2±31.3, P=0.001) significantly increased in comparison with the control group (83.8±14.9). Moreover, liver MDA levels in the ET group (0.38±0.08, P=0.008) and ET + Ginger group (0.37±0.09, P=0.013) significantly increased in comparison with the control group (0.25.0±03). However, 8 weeks of ET coupled with ginger consumption had no effects on the serum levels of AST and ALT (P&gt;0.05). Furthermore, ginger had no effect on MDA level and enzymatic activity of SOD (P&gt;0.05). Conclusion: This study does not support the protective effects of ginger on the reduction of liver enzymes levels and improvement of the antioxidant status

Protective effect of salvianic acid A on hepatic ischemia reperfusion injury in rats

Objective To study the protective effect of salvianic acid A on hepatic ischemia reperfusion (I/R) injury in rats. Methods Sixty SD rats were randomly divided into 3 groups (20 rats in each group): sham operation (Sham) group, I/R group, Salvianic acid A preconditioning (Sal+ I/R) group. The portal vein, hepatic artery and bile duct of the middle lobe and left lobe of the liver were dissected, and clipped by the small blood vessel clamp to make the left and middle lobe ischemia. The blood flow was restored after 1 h, and the model of I/R was constructed. In the sham operation (Sham) group, dissection was done at the same step without blocking blood flow. In Sal+ I/R group, Salvianic acid A (40 mg/kg) was injected through the tail vein 60 min before ischemia. After reperfusion for 6 h, 10 rats were randomly selected from each group. Blood samples were collected through the inferior vena cava and liver tissue samples were taken. After reperfusion for 12 h, the remaining rats were treated by the same method. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were determined. The levels of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were measured in liver tissues. The pathological changes of liver tissue were observed by hematoxylin and eosin (HE) staining and light microscopy. Results The levels of ALT, AST, IL-6 and TNF-α in the Sal+ I/R group [6 h: (350.47±69.65), (500.25±76.12) U/L, (165.32±23.46), (65.31±9.52) ng/L; 12 h: (250.47±36.78), (355.25±59.12) U/L, (130.65±34.31), (103.38±18.46) ng/L were lower than those in the group I/R [6 h: (550.34±82.31), (702.28±106.48) U/L, (300.13±49.28), (95.55±29.21) ng/L; 12 h: (490.34±89.68), (550.28±64.23) U/L, (260.00±60.08), (180.32±38.12) ng/L, P=0.019]; The levels of GPX and SOD in the Sal+ I/R group [6 h: (52.34±11.59), (63.00±19.23) pg/ml; 12 h: (68.32±21.45), (81.00±17.65) pg/ml] were higher than those in the group I/R [6 h: (30.12±5.12), (43.00±7.45) pg/ml; 12 h: (39.58±3.16), (54.00±8.46) pg/ml, P=0.029], the injury of the liver tissue in the Sal+ I/R group was lighter than that in the group I/R under light microscope. Conclusion Salvianic acid A could lower the levels of IL-6 and TNF-α in serum after the I/R injury in rats, raise the levels of GPX and SOD in liver tissue and reduce the degree of liver damage after I/R. Key words: Salvianic acid A; Liver ischemia reperfusion injury; Reactive oxygen species

Expression of aryl hydrocarbon receptor-regulated genes and superoxide dismutase in the Antarctic eelpout Pachycara brachycephalum exposed to benzo[a]pyrene.

The aryl hydrocarbon receptor (AhR) pathway mediates many, if not all, responses of fish to dioxin-like compounds. The Southern Ocean is progressively exposed to increasing concentrations of anthropogenic pollutants. Antarctic fish are known to accumulate those pollutants, yet nothing is known about their capability to induce chemical biotransformation via the AhR pathway. The objective of the present study was to investigate whether Antarctic eelpout, Pachycara brachycephalum, respond to anthropogenic pollutants by activation of the AhR and its target gene cytochrome P4501A (CYP1A), and of superoxide dismutase (SOD), which served as a representative for oxidative stress. We exposed P. brachycephalum to 10 and 100 mg benzo[a]pyrene (BaP)/kg body weight for 10 d and measured the expression of AhR, CYP1A, and SOD in liver tissue via quantitative polymerase chain reaction. We identified two distinct AhR isoforms in the liver of P. brachycephalum. Antarctic eelpout responded to both BaP exposures by an up-regulation of AhR and SOD, and by a particularly strong induction of CYP1A expression, which remained high until day 10 of the exposure time. Our data suggest that P. brachycephalum possesses the potential to up-regulate xenobiotic biotransformation pathways, at least at the gene expression level. The time course of the AhR and CYP1A response points to an efficient but slow xenobiotics metabolism. Moreover, BaP exposure could include adverse effects such as oxidative stress. Environ Toxicol Chem 2018;37:1487-1495. © 2018 SETAC.

Influence of intravenous injected sodium hydrosulfide on fatty liver ischemia-reperfusion injury in rats

Objective To investigate whether intravenous injected sodium hydrosulfide (NaHS) could alleviate the fatty liver ischemia-reperfusion injury in rats and the mechanism. Methods 30 healthy male Sprague-Dawley (SD) rats were fed with high fat diet for 4 weeks then divided into five groups randomly, sham operation group (S group), ischemia-reperfusion group (IR group) and different doses of sodium hydrosulfide groups (NaHS 1-3 groups). In S group hepatic portal was only exposed but not ligated. In IR group the left and middle lobes of hepatic portal vein and hepatic artery were clamped for 1 h and then reperfused. NaHS 1-3 groups received intravenous of NaHS 14, 28, 56 μmol/kg 5 min before reperfusion. Blood samples were collected for measuring the level of alanine transaminase (ALT) in serum at 6 h after reperfusion. Liver tissue samples were collected for measurement the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) and pathologic examination. Results The level of ALT in serum of S group, IR group and NaHS 1-3 group were(64±8), (1 393±69), (852±53), (823±42), (807±57) U/L respectively; The content of MDA in liver tissue of S group, IR group and NaHS 1-3 group were (2.15±0.24), (7.97±0.42), (5.26±0.34), (4.95±0.42), (4.77±0.40) nmol/mg prot respectively; the activity of SOD in liver tissue were (421±20), (201±32), (517±27), (601±23), (607±30) U/mg prot respectively. Compared with S group, the level of ALT in serum and MDA content in liver tissue were increased in IR group (t=44.194, P=0.000; t=42.068, P=0.000), and the activity of SOD in liver tissue was decreased in IR group (t=-14.658, P=0.000). Compared with IR group, the level of ALT in serum were decreased in NaHS 1-3 group (t=-11.563, P=0.000; t=-36.415, P=0.000; t=-13.372, P=0.000), and the content MDA in liver tissue were decreased in NaHS 1-3 group (t=-10.375, P=0.000; t=-17.532, P=0.000; t=-12.402, P=0.000), the activity of SOD in liver tissue was increased in NaHS 1-3 group (t=24.087, P=0.000; t=30.451, P=0.000; t=42.542, P=0.000). The pathological damage degree was lighter in NaHS 1-3 group (Suzuki’s score 2.50, 2.33, 2.17) than IR group (Suzuki’s score 3.67) (t=3.873, P=0.012; t=6.325, P=0.001; t=11.608, P=0.000). Conclusion Intravenous injected sodium hydrosulfide can reduce fatty liver ischemia-reperfusion injury in rats through the inhibition of lipid peroxidation. Key words: Sodium hydrosulfide; Liver ischemia; Reperfusion injury; Fatty liver; Lipid peroxidation

Impact of hepatic blood inflow occlusion without hemihepatic artery control on tumor suppression and liver function in rat liver cancer model

Objective To study the effect of hepatic blood inflow occlusion without hemihepatic artery control on tumor suppression and liver function in rat liver cancer model. Methods Thirty SD rats were randomly divided into total hepatic inflow occlusion control group, hepatic vascular occlusion group, and hepatic blood inflow occlusion without hemihepatic artery control group. Three days after liver cancer moldel was established, the blood flow reperfusion was performed on the livers after 60 min of hepatic vascular occlusion. Five days after reperfusion, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin (ALB), and superoxide dismutase (SOD) and malondialdehyde (MDA) in liver tissues were determined. Liver cell apoptosis rate and tumor suppression rate were calculated. Results In hepatic vascular occlusion group and hepatic blood inflow occlusion without hemihepatic artery control group, serum ALT and AST levels were significantly lower, and ALB levels were significantly higher than in control group [(70.97±8.62) vs. (72.04±8.54) vs. (268.26±46.39) IU/L, (386.86±50.28) vs. (392.53±22.47) vs. (1 109.24±279.35) IU/L, (29.54±2.16) vs. (28.63±2.27) vs. (25.29±2.13) g/L, t=13.222, 8.048, 4.430, 13.151, 8.087 and 3.393, P=0.001, 0.008, 0.018, 0.000, 0.008, 0.024]. In hepatic vascular occlusion group and hepatic blood inflow occlusion without hemihepatic artery control group, liver tissue SOD levels were significantly higher, and MDA and liver cell apoptosis rate were significantly lower than in control group [(152.32±16.21) vs. (148.47±15.24) vs. (89.12±9.45) U/mgprot, (18.36±3.14) vs. (19.32±2.95) vs. (48.36±5.23) nmol/mg, (14.35±1.45)% vs. (15.12±1.54)% vs. (25.14±2.14)%, t=10.651, 15.552, 13.200, 10.466, 15.294 and 12.018, P=0.001, 0.001, 0.001, 0.001, 0.001, 0.001]. In hepatic vascular occlusion group and hepatic blood inflow occlusion without hemihepatic artery control group, tumor weight was significantly reduced as compared with control group [(1.83±0.32) vs. (1.90±0.35) vs. (2.62±0.41) g, t=4.803, and 4.224, P=0.008, 0.018]. There were no statistically significant differences in ALT, AST, SOD, MDA, liver cell apoptosis rate, tumor weight, and tumor suppression rate between hepatic vascular occlusion group and hepatic blood inflow occlusion without hemihepatic artery control group. Conclusion Hepatic blood inflow occlusion without hemihepatic artery control can reduce liver ishemia-reperfusion injury in rat liver cnacer model, promote tumor suppression effect, and the operation security is higher than hepatic vascular occlusion. Key words: Carcinoma, hepatocellular; Ischemia-reperfusion; Hepatic blood inflow occlusion without hemihepatic artery control; Liver function

L-carnitine alleviates liver warm ischemia-reperfusion injury in rats through activating Nrf2/HO-1 pathway

Objective To investigate the protective effects of L-carnitine on liver warm ischemia-reperfusion injury (WIRI) in rats and to explore its possible role of L-carnitine in affecting Nrf2/HO-1 pathway. Methods Twenty-four male Sprague-Dawley (SD) rats were randomly divided into three groups including sham-operated (SO) group, liver warm ischemia and reperfusion (WIR) group and L-carnitine pretreatment (LC) group. L-carnitine was injected intraperitoneally in LC group while the equal volume of saline was injected in SO group and WIR group. The levels of ALT and AST in serum as well as the activities of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in liver tissues were detected. Meanwhile, pathologic change of liver tissue was observed. And then, the mRNA expression of NF-E2-related factor 2(Nrf2) and heme oxygenase 1(HO-1) in liver tissues was determined. Results Compared with the SO group, ALT and AST level in serum were significantly increased (P<0.05) in the WIR group; the activity of SOD in liver tissues was significantly reduced in the WIR group [(66.6±12.3) U/mgprot vs. (25.1±9.0) U/mgprot, P<0.05]; and the content of MDA in liver tissues was significantly increased in the WIR group [(1.5±0.3) nmol/mgprot vs. (3.6±0.8) nmol/mgprot, P<0.05]; the mRNA expression of Nrf2 and HO-1 were significantly increased (P<0.05) in the WIR group. Compared with the WIR group, ALT and AST level in serum were significantly reduced (P<0.05) in the LC group; the activity of SOD in liver tissues was significantly increased in the LC group [(25.1±9.0) U/mgprot vs. (86.0±11.4) U/mgprot, P<0.05)]; and the content of MDA in liver tissues was significantly reduced in the LC group [(3.6±0.8) nmol/mgprot vs. (1.4±0.2)nmol/mgprot, P<0.05]; the mRNA expression of Nrf2 and HO-1 were significantly increased (P<0.05) in the LC group. Conclusion L-carnitine may attenuate liver WIRI in rats, and this protective effect may be through activating the Nrf2/HO-1 pathway. Key words: L-Carnitine; Liver warm ischemia-reperfusion injury; Nrf2; HO-1; Oxidative stress

Protective role of silymarin and D-penicillamine against lead-induced liver toxicity and oxidative stress.

This study was performed to assess hepatotoxicity and alterations in liver antioxidant defence in acute lead (Pb) exposure and the protective effects of silymarin in comparison to D-penicillamine in rats. Forty eight Albino rats were divided in eight groups and received the following treatments in a 10-day experiment - group 1: normal saline as control; group 2: 25-mg/kg Pb acetate, intraperitoneally (IP) for the last 5 days; group 3: 100-mg/kg D-penicillamine, IP for the last 5 days; group 4: 200-mg/kg silymarin, orally for 10 days; and groups 5, 6, 7 and 8: in addition to Pb, they received D-penicillamine, for the last 5 days, silymarin for 10 days, a combination of silymarin for 10 days and D-penicillamine for the last 5 days and silymarin for the last 5 days, respectively. Pb acetate exposure induced significant elevation in serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities in group 2 compared to control group. Significant reductions in serum total protein and albumin in all Pb-exposed groups and in serum glucose in groups 2, 6 and 8 were also observed. Liver tissue superoxide dismutase and glutathione peroxidase were significantly lower in groups 2 and 8 compared to control group. Silymarin pretreatment and D-penicillamine administration in groups 5, 7 and 8 could significantly lower ALP, ALT and AST and improve liver antioxidant enzymes. Thus, acute Pb exposure induced hepatotoxicity with suppression of liver antioxidant defence system and silymarin, as an antioxidant could alleviate this effect.

Effects of the Fomes officinalis flavonoids on anti-senile action in the aging model mice

To study the anti-senile effects of the Fomes officinalis flavonoids on the aging model mice. All Kun ming mice were randomly divided into six groups, and each group consisted of 12 animals. The groups were categorized as normal, model, positive control groups and low (100 mg/(kg·d)), medium (200 mg/(kg·d)), high (400 mg/(kg·d)) doses of Fomes officinalis flavonoids treated groups. The study was carried out to investigate the cerebral index, spleen index, thymus index, the contents of malondi-aldehyde (MDA) and the activities of glutathione peroxidase (GSH-Px) in brain tissues as well as the activities of catalase (CAT) and superoxide dismutase (SOD) in liver tissues of the aging model mice treated with D-galactose in vivo by subcutaneous injection together with the Fomes officinalis flavonoids at doses of 100, 200 and 400 mg/(kg·d) for 6 weeks. The normal group was administered with 0.20 ml/10 g of normal saline s.c. and 50 ml/kg of normal saline i.g. daily. Compared with the aging model groups, the three doses of the Fomes officinalis flavonoids could elevate the cerebral index, spleen index, thymus index, activities of GSH-Px in brain tissues, the activities of CAT and SOD in liver tissues to different degree and decrease the contents of MDA. The Fomes officinalis flavonoids might have anti-senile action by improving antioxidant capacity of human body.

English

In this study we investigated if ghrelin plays a protective role against paracetamol-induced acute hepatotoxicity in rats and the possible mechanism of action. Forty adult male albino rats were divided into four equal groups; control, ghrelin, paracetamol and ghrelin plus paracetamol. Evaluations were made for lipid peroxidation, enzyme activities and biochemical parameters. Liver histopathology was also performed. Paracetamol (PCM) treatment increased plasma and liver tissue malondialdehyde (MDA) content and plasma nitric oxide (NO) level, and decreased erythrocyte and liver tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities when compared to control group. At the same time, PCM treatment increased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities. By contrast, ghrelin pretreatment reduced plasma and liver MDA content and plasma NO level, and increased erythrocyte, liver tissue SOD, CAT and GPx activities when compared with paracetamol-treated group. The PCM-induced histopathological changes were also reduced by the ghrelin pretreatment. In conclusion, our results proved that ghrelin was found to protect the liver against paracetamol-induced oxidative damage in rats and the hepatoprotective effect may be correlated with its antioxidant effect. &nbsp; Key words: Antioxidant, ghrelin, hepatoprotective, hepatotoxicity, paracetamol.