Liver Transaminase Activities Research Articles

Relationship between butyrylcholinesterase activity and hepatic transaminases: a cross-sectional study in agricultural workers from Peru

IntroductionChronic exposure to pesticides causes various adverse health effects, mainly at a neurological level. However, there is little evidence focused on liver tissue injury and transaminase activity as indicators of effect.MethodsA cross-sectional study was designed based on medical-occupational records of workers from an agro-export company in Peru to associate the levels of butyrylcholinesterase (BChE) transaminases (ALT and AST). Occupational medical records were reviewed to obtain demographic and occupational information and laboratory values of BChE activity and transaminases.ResultsWe evaluated 459 records, and 69.9% were men. The mean age was 34.9 ± 11.5 years. BChE, ALT, and AST levels were 6238.8 ± 709.1 U/l, 34.4 ± 12.5 U/l, and 22.4 ± 8.5 U/l, respectively. The proportion of inhibited BCHE and elevated transaminase levels was 15.3% and 21.6%, respectively. We found a significant association between BChE inhibition and elevation of transaminases (AST: PR = 0.798, 95%CI: 0.716–0.889; ALT: PR = 0.419, 95%CI: 0.239–0.736).ConclusionThe potential usefulness of transaminases is shown as a biomarker of exposure and monitoring in occupational health programs for the agro-industry.

CD69 Expression is Negatively Associated With T-Cell Immunity and Predicts Antiviral Therapy Response in Chronic Hepatitis B.

The function of CD69 expressed on T cells in chronic hepatitis B (CHB) remains unclear. We aimed to elucidate the roles of CD69 on T cells in the disease process and in antiviral therapy for CHB. We enrolled 335 treatment-naive patients with CHB and 93 patients with CHB on antiviral therapy. CD69, antiviral cytokine production by T cells, T-helper (Th) cells, and inhibitory molecules of T cells were measured using flow cytometry, and clinical-virological characteristics were examined dynamically during antiviral therapy. CD69 expression on CD3+, CD4+, and CD8+ T cells was the lowest in the immune-active phase and was negatively correlated with liver transaminase activity, fibrosis features, inflammatory cytokine production by T cells, and Th-cell frequencies but positively with inhibitory molecules on T cells. CD69 expression on CD3+, CD4+, and CD8+ T cells decreased after 48 weeks of antiviral therapy, and patients with hepatitis B e antigen (HBeAg) seroconversion in week 48 showed lower CD69 expression on T cells at baseline and week 48. The area under the ROC curve of CD69 expression on T cells at baseline for predicting HBeAg seroconversion in week 48 was 0.870, the sensitivity was 0.909, and the specificity was 0.714 (P =0.002). CD69 negatively regulates T-cell immunity during CHB, and its expression decreases with antiviral therapy. CD69 expression predicts HBeAg seroconversion in week 48. CD69 may play an important negative role in regulating T cells and affect the efficacy of antiviral therapy.

Effect of Hibiscus sabdariffa L. leaf flavonoid-rich extract on Nrf-2 and HO-1 pathways in liver damage of streptozotocin-induced diabetic rats.

This study investigated the effects of flavonoid-rich extract from Hibiscus sabdariffa L. (Malvaceae) leaves on liver damage in streptozotocin-induced diabetic rats by evaluating various biochemical parameters, including the molecular gene expressions of Nrf-2 and HO-1 as well as histological parameters. The extract was found to significantly reduce liver damage, as evidenced by lower levels of fragmented DNA and protein carbonyl concentrations. Oxidative stress markers, including malondialdehyde (MDA) level, were also significantly (p<0.05) decreased, while antioxidant biomarkers, like reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were enhanced. Additionally, the extract improved the activities of key liver enzymes, including phosphatases and transaminases, and increased albumin levels. Importantly, the study demonstrated that H.sabdariffa extract effectively regulated the expression of Nrf-2 and HO-1, suggesting a significant role in mitigating liver damage. These findings highlight its potential as a therapeutic agent for liver protection in diabetic conditions.

Impact of dietary zinc on the growth performance, histopathological analysis, antioxidant capability, and inflammatory response of largemouth bass Micropterus salmoides

Zinc plays a crucial role in the antioxidant capacity, and inflammatory response of aquatic species, but its impact on largemouth bass Micropterus salmoides is rarely reported. Therefore, this paper aimed to investigate the effects of different levels of zinc on the growth performance, histopathology, antioxidant capacity, and inflammatory cytokines of largemouth bass Micropterus salmoides. Fish with an initial weight of 7.84 ± 0.06 g were cultured for 10 weeks. Five experimental diets were prepared with supplemented proteinate Zn (Bioplex Zn, Alltech) (0, 30, 60, 90, and 120 mg/kg), which were named the Zn-42, Zn-73, Zn-103, Zn-133, and Zn-164 groups. No evident difference was found between the dietary zinc level and the survival rate, the crude lipid content of the whole fish, or the visceral somatic index. Weight gain, condition factor, whole-body crude protein content, interleukin-10, and transforming growth factor beta gene expression were gradually enhanced with up to 102.68 mg/kg zinc and decreased at higher levels. The hepatosomatic index, feed conversion ratio, malondialdehyde level in the liver, aspartate aminotransferase, and alanine transaminase activity in the serum, gradually decreased up to 102.68 mg/kg zinc, and gradually increased beyond this. Activation of the nuclear factor erythroid-derived 2-like 2/Kelch-like ECH-associated protein 1 signaling pathway gradually up-regulated the mRNA levels and activities of glutathione peroxidase, total antioxidant capacity, catalase, and superoxide dismutase in the liver, this antioxidant ability was lower when the zinc was greater than 102.68 mg/kg. The gene expressions of nuclear factor-k-gene binding and pro-inflammation cytokines (interleukin-1β, interleukin-15, tumor necrosis factor alpha, and interleukin-8) were up-regulated up to 102.68 mg/kg zinc and then gradually repressed. In conclusion, using broken line analysis to estimate weight gain and Zn proteinate as the zinc source, the recommended dietary zinc for largemouth bass is 66.57 mg/kg zinc.

Clinical and genetic spectrum of GSD type 6 in Korea

BackgroundGlycogen storage disease type VI (GSD VI) is a rare disease in which liver glycogen metabolism is impaired by mutations in the glycogen phosphorylase L (PYGL). This study aimed to examine the clinical features, genetic analyses, and long-term outcomes of patients with GSD VI in Korea.MethodsFrom January 2002 to November 2022, we retrospectively reviewed patients diagnosed with GSD VI using a gene panel at Seoul National University Hospital. We investigated the clinical profile, liver histology, molecular diagnosis, and long-term outcomes of patients with GSD VI.ResultsFive patients were included in the study. The age at onset was 18–30 months (median, 21 months), and current age was 3.7–17 years (median, 11 years). All patients showed hepatomegaly, elevated liver transaminase activity, and hypertriglyceridaemia. Hypercholesterolaemia and fasting hypoglycaemia occurred in 60% and 40% of patients, respectively. Ten variants of PYGL were identified, of which six were novel: five missense (p.[Gly607Val], p.[Leu445Pro], p.[Gly695Glu], p.[Val828Gly], p.[Tyr158His]), and one frameshift (p.[Arg67AlafsTer34]). All patients were treated with a high-protein diet, and four also received corn starch. All patients showed improved liver function tests, hypertriglyceridaemia, hepatomegaly, and height z score.ConclusionsThe GSD gene panel is a useful diagnostic tool for confirming the presence of GSD VI. Genetic heterogeneity was observed in all patients with GSD VI. Increased liver enzyme levels, hypertriglyceridaemia, and height z score in patients with GSD VI improved during long-term follow-up.

Effect of Nutmeg on Transaminase Activities in Liver and Serum of Adult Wistar rats

This study examines the activities of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) in the liver of 30 adult Wistar rats exposed to nutmeg for 30 days. 1 g of nutmeg was administered to group A (n=10), 2 g of nutmeg to group B (n=10) and group C (n=10) was used as the control. Enzyme activities were assayed in both serum and liver (tissue homogenate) spectrophotometrically. Results obtained showed a significant increase (p &lt; 0.05) in level of AST in serum of rats in group A and B (20.2±7.29 and 23.2 ± 3.27 U/L) when compared to the control group (14.8± 1.78 U/L) while serum ALT level was significantly reduced (5.2± 1.78 and 4.2 ± 0.04 U/L) compared to the control group (7.0 ± 2.6 U/L) but the differences based on dosage was statistically insignificant (p≥ 0.05). The enzyme activities in liver tissue homogenate showed a significant increase (p˂ 0.05) in AST levels (13.8 ± 1.14, 14.6 ± 1.78 and 12.8 ± 0.08 U/L) among test groups and between controls but ALT levels though lower in treated groups than control, was statistically insignificant (p≥ 0.05) among test and between control group (4.6 ± 1.34, 4.0 ± 0.08 and 5.8 ± 0.03 U/L). Differences in enzyme activities due to nutmeg administration may lead to hepatocellular injury as well as myocardial infarction. The results suggests that dosage and long-term consumption of nutmeg could have severe health implication as it affects liver function as well as other associated organ of the body.

Experience of using lumacaftor/ivacaftor in children with cystic fibrosis in the Astrakhan region

Background. Targeted therapy in patients with cystic fibrosis, which aims to restore the function of the cystic fibrosis transmembrane conductance regulator protein, is currently revolutionary in the treatment of the disease. The first drug available in Russia for the treatment of patients with this genetic disease is lumacaftor/ivacaftor (Orkambi®), which was registered on December 2, 2020.The aim. To study the efficacy of lumacaftor/ivacaftor during 12 weeks of administration in children in Astrakhan region.Materials and methods. This article presents the clinical experience of Orkambi medicine use in 3 children with F508del/F508del genotype and a severe course of cystic fibrosis for 12 weeks. According to the study design, such indices as body mass index, indexes of external respiratory function, character of respiratory tract microbiota, level of chloride in sweat fluid and pancreatic elastase in feces, dynamics of biochemical blood indexes were evaluated. The study was performed within the time periods specified in the study protocol, namely, before the start of therapy, 2, 4, and 12 weeks of treatment.Results. Two patients had a decrease in sweat test values by 11 and 19 mmol/l from the baseline, a significant increase in forced vital capacity of lungs. One patient had an adverse event in the form of hepatobiliary disorders manifested by increased liver transaminase activity, which was the reason for discontinuing the drug.Conclusions. The short-term experience of using pathogenetic therapy with lumacaftor/ ivacaftor in children in the Astrakhan region demonstrated both the expected effect on chlorine channel function and the possibility of side effects, including severe ones, that can lead to withdrawal of the drug.

Deuterium-Reinforced Polyunsaturated Fatty Acids Prevent Diet-Induced Nonalcoholic Steatohepatitis by Reducing Oxidative Stress.

Background and Objectives: Oxidative stress is implicated in the progression of nonalcoholic steatohepatitis (NASH) through the triggering of inflammation. Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to the reactive oxygen species (ROS)−initiated chain reaction of lipid peroxidation than regular hydrogenated (H−) PUFAs. Here, we aimed to investigate the impacts of D-PUFAs on oxidative stress and its protective effect on NASH. Materials and Methods: C57BL/6 mice were randomly divided into three groups and were fed a normal chow diet, a methionine–choline-deficient (MCD) diet, and an MCD with 0.6% D-PUFAs for 5 weeks. The phenotypes of NASH in mice were determined. The levels of oxidative stress were examined both in vivo and in vitro. Results: The treatment with D-PUFAs attenuated the ROS production and enhanced the cell viability in tert-butyl hydroperoxide (TBHP)−loaded hepatocytes. Concurrently, D-PUFAs decreased the TBHP-induced oxidative stress in Raw 264.7 macrophages. Accordingly, D-PUFAs increased the cell viability and attenuated the lipopolysaccharide-stimulated proinflammatory cytokine expression of macrophages. In vivo, the administration of D-PUFAs reduced the phenotypes of NASH in MCD-fed mice. Specifically, D-PUFAs decreased the liver transaminase activity and attenuated the steatosis, inflammation, and fibrosis in the livers of NASH mice. Conclusion: D-PUFAs may be potential therapeutic agents to prevent NASH by broadly reducing oxidative stress.

Syringic acid and silymarin concurrent administration inhibits sodium valproate-induced liver injury in rats.

Sodium valproate (SV) is a well-known anti-epileptic drug, also used to control convulsions, bipolar disorders and migraines. SV has been shown to induce liver toxicity in clinical subjects. Syringic acid (SA), a natural polyphenolic compound has potential antioxidant, anti-inflammatory and several beneficial effects. Therefore, in this study, we evaluated hepatoprotective effect of SA against SV-induced liver injury in rats. Wistar rats were treated with SV orally at a dose of 500 mg/kg, once daily, for 14 days. Another three groups of rats were administered with SV and concurrently treated with SA (40 and 80 mg/kg) and silymarin (SIL) (100 mg/kg) for 14 days. SV administration for 14 days caused significant (p < .001) elevation of liver transaminases and ALP in serum. Liver MDA level was significantly (p < .001) increased with a concomitant decrease (p < .001) in enzymic antioxidants activities in SV administered rats. SV administration also caused the upregulation of proinflammatory markers such as tumor necrosis factor α, c-Jun N-terminal kinase, nuclear factor kappa B, cyclooxygenase-2 and Interleukin 6 expressions in liver tissue. Histopathological studies also revealed the presence of inflammatory cell infiltration and hepatocellular necrosis upon SV administration. At both doses, concurrent administration of SA and SIL significantly (p < .001) inhibited the liver transaminase activities in serum, oxidative stress, and proinflammatory markers expression in liver tissue. Our current results suggest that SA can be a promising herbal drug that can inhibit SV-induced hepatotoxicity when administered together due its potential anti-inflammatory effects.

Lipoic Acid Exacerbates Oxidative Stress and Lipid Accumulation in the Liver of Wistar Rats Fed a Hypercaloric Choline-Deficient Diet.

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.

A mycotoxin-deactivating feed additive counteracts the adverse effects of regular levels of Fusarium mycotoxins in dairy cows

Little is known about the effects of commonly found levels of Fusarium mycotoxins on the performance, metabolism, and immunity of dairy cattle. We investigated the effects of regular contamination levels, meaning contamination levels that can be commonly detected in dairy feeds, of deoxynivalenol (DON) and fumonisins (FB) in total mixed ration (TMR) on the performance, diet digestibility, milk quality, and plasma liver enzymes in dairy cows. This trial examined 12 lactating Holstein dairy cows using a 3-period × 3-treatment Latin square design. The experimental period was 21 d of mycotoxin exposure followed by 14 d of washout. During treatment periods, cows received one of 3 diets: (1) CTR (control) diet of TMR contaminated with 340.5 µg of DON/kg of dry matter (DM) and 127.9 µg FB/kg of DM; (2) MTX diet of TMR contaminated with Fusarium mycotoxins at levels higher than CTR but below US and European Union guidelines (i.e., 733.0 µg of DON/kg of DM and 994.4 µg of FB/kg of DM); or (3) MDP diet, which was MTX diet supplemented with a mycotoxin deactivator product (i.e., 897.3 µg of DON/kg of DM and 1,247.1 µg of FB/kg of DM; Mycofix, 35 g/animal per day). During washout, all animals were fed the same CTR diet. Body weight, body condition score, DM intake, dietary nutrient digestibility, milk production, milk composition and rennet coagulation properties, somatic cell count, blood serum chemistry, hematology, serum immunoglobulin concentrations, and expression of multiple genes in circulating leucocytes were measured. Milk production was significantly greater in the CTR group (37.73 kg/d) than in the MTX (36.39 kg/d) and the MDP (36.55 kg/d) groups. Curd firmness and curd firming time were negatively affected by the MTX diet compared with the other 2 diets. Furthermore, DM and neutral detergent fiber digestibility were lower after the MTX diet than after the CTR diet (67.3 vs. 71.0% and 42.8 vs. 52.3%). The MDP diet had the highest digestibility coefficients for DM (72.4%) and neutral detergent fiber (53.6%) compared with the other 2 diets. The activities of plasma liver transaminases were higher after the MTX diet than after the CTR and MDP diets. Compared with the CTR diet, the MTX diet led to slightly lower expression of genes related to immune and inflammatory functions, indicating that Fusarium mycotoxins had an immunosuppressive effect. Our results indicated that feed contaminated with regular levels of Fusarium mycotoxins adversely affected the performance, milk quality, diet digestibility, metabolic variables, and immunity of dairy cows, and that supplementation with mycotoxin deactivator product counteracted most of these negative effects.

Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases.

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.

Delayed onset of liver injury after intentional chloroform overdose: a case report and literature review

Chloroform is a recognised cause of acute liver injury, although now rarely encountered in clinical practice. We present a case of inhalational chloroform self-poisoning in a 47-year-old man that presented to hospital initially with reduced conscious level and later developed acute liver injury that was treated with intravenous acetylcysteine. This paper reviews the existing literature and presents a summary of the mechanisms of chloroform hepatotoxicity. Published cases show that there is a characteristic delay of 24 to 48 hours between chloroform exposure and elevation of liver transaminase activity. Therefore, clinicians need to provide an appropriate duration of monitoring in order to detect the occurrence of this important toxic effect.

Potential of Regular Consumption of Cameroonian Neem (Azadirachta indica L.) Oil for Prevention of the 7,12-Dimethylbenz(a)anthracene-Induced Breast Cancer in High-Fat/Sucrose-Fed Wistar Rats.

Neem (Azadirachta indica) is a tree from the Meliaceae family native to India, where it is considered as one of the most important plants worldwide. The anticancer effects of neem oil on breast cancer cells have been recently reported; however, its in vivo effects have not been studied. This prompted us to investigate the protective effects of neem oil on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer in high-fat/sucrose-fed Wistar rats. Juvenile female Wistar rats were treated either with neem oil at a dose of 3 mL/kg body weight at 3 different frequencies, 2 times/week (Neem 1), 4 times/week (Neem 2), and every day (Neem 3), or with tamoxifen (3.3 mg/kg body weight), starting 1 week prior to DMBA treatment and lasting 12 weeks. Incidence, burden, volume, and histological analysis of mammary tumors were measured. Further toxicological parameters have been assessed. No tumors were detected in rats from the normal group, while all the rats from the negative control group (100%) developed mammary tumors. The regular consumption of neem oil at a dose of 3 mL/kg (2 or 4 times/week) significantly (p < 0.01) and in a dose-dependent manner reduced tumor incidence (80%), burden [35.78% (2 times/week) and 36.09% (4 times/week)], and weight. Neem consumption protected rats against DMBA-induced breast hyperplasia, with an optimal effect when taken 4 times weekly. Interestingly, all the animals that received a daily dose of 3 mL/kg died at the third week of the experiment. Further, animals that took the neem oil 4 times per week developed hepatotoxicity, evidenced by an increase of liver wet weight, transaminase (ALT and AST) activity, and histological abnormalities in liver. This study brings insight into the use of neem oil, which is greatly appreciated in traditional medicine. In summary, we demonstrated for the first time that the regular consumption of neem oil prevents breast cancer, but its excessive consumption is toxic.

Effect of CAPE-pNO2 against type 2 diabetes mellitus via the AMPK/GLUT4/ GSK3β/PPARα pathway in HFD/STZ-induced diabetic mice

CAPE-pNO2, a para-nitro derivative of caffeic acid phenethyl ester (CAPE), has been proved to exert stronger effects on diabetic complications in diabetic mice. The present study aimed at probing into the effect and potential mechanism of CAPE-pNO2 in type 2 diabetes mellitus (T2DM) compared with CAPE on model animal. Diabetic model was established by feeding one month of high-fat-diet (HFD) before injection of 40 mg/kg streptozotocin (STZ) for five days, and the normal diet mice were set as control group. Model mice were treated by CAPE-pNO2 for one month again, the levels of blood glucose, blood lipid and blood insulin significantly decreased. In addition, the myocardial enzymes (creatine Kinase and lactate dehydrogenase) and liver transaminase (aspartate aminotransferase and alanine aminotransferase) activities decreased. Furthermore, CAPE-pNO2 could alleviate pancreatic damage, myocardial injury and hepatic steatosis caused by diabetes mellitus, and significantly improved the islet mass, β cell survival and the hepatic glycogen content. Besides, CAPE-pNO2 enhanced the expression of phosphorylation-AMP-activated protein kinas (p-AMPK) (Thr172), GLUT4, peroxisome proliferator-activated receptor-α (PPARα) and p-Akt (Ser473), and inhibited the expression of glycogen synthase kinase 3β (GSK3β) and p-JNK (Thr183/Tyr185) in liver. All of those effects are better than CAPE generally. It suggested that CAPE-pNO2 ameliorated type 2 diabetes mellitus by effectively protecting islet β cell and improving the insulin resistance via the AMPK/GLUT4/GSK3β/PPARα pathway.

Protective Effects of Ischemic Preconditioning Protocols on Ischemia-Reperfusion Injury in Rat Liver

Background: Hepatic ischemia reperfusion injury often leads to increased complications and mortality after surgery. Although ischemic preconditioning is used as a convenient and effective method to protect the liver from warm ischemia reperfusion injury, the optimal protocol is currently unclear. Therefore, in this study, we sought to identify ideal conditions and methods for ischemic preconditioning. Materials and methods: We compared several preconditioning protocols of the ischemia/reperfusion (I/R) cycle in 30 male Sprague-Dawley rats (5 groups, n = 6), including relevant sham and I/R injury (no preconditioning) controls. Experimental group conditions included: (1) ischemia for 5 min/reperfusion for 10 min (ischemic preconditioning 1, IPC-1); (2) ischemia for 5 min/reperfusion for 5 min, repeated three times (IPC-2); and (3) ischemia for 10 min/reperfusion for 10 min (IPC-3). Readouts included transaminase activity levels measured from collected sera, and histopathological changes, liver cell apoptosis, superoxide dismutase (SOD) activity, glutathione (GSH) levels, and malondialdehyde (MDA) levels measured from collected liver tissue segments subjected to warm ischemia (that is from the 70% of the liver mass that had been deprived from blood flow during the ischemia phase). Results: Compared to the I/R control group, the IPC-1, IPC-2, and IPC-3 groups all showed significant decreases in liver transaminase activity levels, alleviation of pathological injury-associated changes, and a decrease in liver cell apoptosis. Moreover, SOD activity and GSH content were increased while MDA content was decreased in the three experimental groups. Compared to the IPC-1 and IPC-3 groups, the changes in the IPC-2 group were the most significant (P < 0.05). Conclusions: Ischemic preconditioning can reduce hepatic warm ischemia reperfusion injury in rats. The IPC-2 protocol, involving ischemia for 5 min and reperfusion for 5 min, repeated three times, provided the optimal protection against hepatic ischemia reperfusion injury among the protocols studied.

MFGE8 protects against CCl4 -induced liver injury by reducing apoptosis and promoting proliferation of hepatocytes.

Milk fat globule-EGF factor 8 (MFGE8) has been reported to play various roles in acute injury and inflammation response. However, the role of MFGE8 in liver injury is poorly investigated. The present research was designed to clarify the expression and function of MFGE8 in carbon tetrachloride (CCl4 )-induced liver injury. Using serum cytokine arrays, we selected a promising cytokine MFGE8 as the candidate in the process of hepatitis-fibrosis-hepatocellular carcinoma (HCC) progression, based on the elevated expression in both hepatic fibrosis and HCC models. We validated the increased expression of MFGE8 in liver tissues and serum samples of acute and chronic CCl4 -induced mice. Immunohistochemistry staining of mouse liver tissues indicated that elevated MFGE8 expression was mainly derived from the injured hepatocytes. In addition, MFGE8 expression in the supernatant of primary hepatocytes was accumulated with prolongation of culture time, and CCl4 treatment further increased the expression of MFGE8. Moreover, a strong correlation between serum MFGE8 expression and liver transaminase activities suggested that MFGE8 may be a novel candidate in liver injury. Intriguingly, mice pretreated with MFGE8 were protected from CCl4 -induced liver injury through antiapoptosis role in the early stage and proproliferation role in the late stage. MFGE8 reduced apoptosis by inhibiting the activation of IRE1α/ASK1/JNK pathway and promoted proliferation by phosphorylation of ERK and AKT. Moreover, serum MFGE8 expression was increased in hepatitis patients while decreased in liver cirrhosis patients. All the results suggest MFGE8 as a novel marker and promising therapeutic agent of liver injury.

Impact of salinity and flaxseed oil -enriched diet on growth and some enzyme activity of Nile tilapia Oreochromis niloticus

This study was conducted to evaluate the effect of flaxseed oil as a source of omega 3 and salinity factor on growth and some enzyme activity Nile tilapia (Oreochromis niloticus) (mean initial weight 1.18 ± 0.1 g ) in indoor recycle aquarium tanks for 45 days. Results showed that adding flaxseed oil and salinity factors did not alter negatively the growth rate of Nile tilapia. Also, our data showed that fish in salinity group exhibited higher aspartate transaminase and alanine transaminase activities in liver while decreased in the flaxseed oil groups in comparison with the control. In conclusion, rearing Nile tilapia in brackish water can be a viable substitute to fresh water in Nile tilapia aquaculture without affecting the growth of tilapia. Moreover, flaxseed oil could be a viable substitute to the fish oil in Nile tilapia aquaculture without affecting the growth of tilapia. Most importantly, salinity factor can improve some enzyme activities such as ALT and AST in liver of Nile tilapia. .

Characterization and hypoglycemic effect of a neutral polysaccharide extracted from the residue of Codonopsis Pilosula

A neutral polysaccharide coded as CERP1 was extracted and purified from the residue of Codonopsis pilosula by ethanol precipitation and column chromatography. The structure of CERP1 was determined by HPAEC-PAD, HPLC, HPSEC-MALLS, FT-IR, NMR, and TEM. The results showed that CERP1 was a heteropolysaccharide composed of Arabinose, Glucose, and Galactose in the ratio of 1.00:19.83:6.94. HPSEC-MALLS showed that CERP1 was homogeneous with an absolute molecular weight of 4.840 × 103 Da. The NMR results and the GC–MS result of methylation indicated that 1-linked β-d-glucose, 1,3-linked β-d-glucose, 1,6-linked β-d-glucose and 1,3,6-linked β-d-galactose were the main linkages in CERP1. TEM results indicated that CERP1 had a homogeneous particle size and good dispersibility both in purified water and 0.05 M sodium sulfate. Pre-treatment with CERP1 could result in a significant improvement of the insulin secretion of the INS-1 cells. While in vivo assays, CERP1 exhibited a potent hypoglycemic effect on T2DM mice for its ability to relieve oxidative stress, ameliorate lipid metabolism, increase glycolytic enzyme activity as well as decrease liver transaminase activity. This study gives a chance for exploring the residue of Codonopsis pilosula.

Impact of loss of SOAT2 function on disease progression in the lysosomal acid lipase-deficient mouse

Although only a small proportion of cholesterol in the body is esterified, in several diseases marked expansion of the esterified cholesterol (EC) pool occurs. These include Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD) which both result from mutations in LIPA, the gene that encodes lysosomal acid lipase (LAL). The respective contributions that our three cholesterol esterifying enzymes make to EC production, especially in disorders like CESD, are not well defined. The current studies represent a detailed exploration of our earlier findings in young male LAL-deficient mice also missing sterol O-acyltransferase 2 (SOAT2, also called ACAT2). Here we show that, even as they aged, male and female Lal−/−: Soat2− /− mice, compared to Lal−/−: Soat2+/+ littermates, had appreciably less hepatomegaly as well as a marked reduction in the level of sequestration of EC, in liver transaminase activities, and in hepatic mRNA expression levels for markers of inflammation. Loss of SOAT2 function also dramatically curtailed EC entrapment in the small intestine of the LAL-deficient mice. Together, these data imply that SOAT2 inhibition, if applied concurrently with enzyme replacement therapy for LAL deficiency, may blunt the re-esterification of newly released unesterified cholesterol thereby improving clinical outcomes.