Serum Transaminase Activities Research Articles

Dietary L-carnitine supplementation recovers the hepatic damage induced by high-fat diet in Nile tilapia (Oreochromis niloticus L.) via activation of Nrf2/Keap pathway and inhibition of pro-inflammatory cytokine.

A feeding trial for 8weeks was performed to explore whether nutritional supplementation of L-carnitine may minimize the adverse effects of high-fat diet (HFD) on tilapia growth performance, antioxidant, immune parameters, inflammatory response, histopathology of liver, kidney, and intestine, as well as hepatic lipid metabolism aiming to reveal the mechanism and providing a shred of molecular evidence in Nile tilapia (Oreochromis niloticous). Six groups of the Nile tilapia (17.13 0.49g) in triplicate were fed for 60days. Six experimental diets were formulated, incorporating different concentrations of L-carnitine. The first three groups were administered a diet comprising 6% fat, with L-carnitine concentrations of 0, 0.5, and 1g/kg diet was designated as F6Car0, F6Car0.5, and F6Car1, respectively. Moreover, the fourth, fifth, and sixth groups were fed on a diet containing 12% fat, with L-carnitine concentrations of 0, 0.5, and 1g/kg diet, respectively termed F12Car0, F12Car0.5, and F12Car1. The main results were as follows: compared to the control group HFD caused a significant reduction in BWG and PER (P > 0.05), but significantly increased the feed conversion rate (FCR), hepatosomatic index (HSI), intraperitoneal fat (IPF), as well as increased visceral fat deposits and liver fat accumulation with higher activities of serum aminotransferases, glucose, triglycerides, and cholesterol. HFD exacerbates hepatic lipid accumulation by enhancing lipogenic gene expression. HFD-fed fish exhibited the lowest crude protein and highest crude fat levels. This study demonstrates that dietary supplementation with L-carnitine significantly boosts growth, improves hemato-biochemical parameters, decreases lipogenesis, elevates lipolysis pathway genes, and lowers lipid levels, thereby rebalancing lipid metabolism and lessening hepatic steatosis. It also mitigates inflammation by downregulating pro-inflammatory genes, upregulating immune genes, and positively affecting Nile tilapia's histopathology.

Biochemical targets of chick embryos affected by sub-lethal concentrations of lambda-cyhalothrin and imidacloprid.

The insecticides Lambda-cyhalothrin (LCT) and imidacloprid (IMD) are extensively utilized in Egyptian agriculture. Embryonic chicken is a readily accessible model organism commonly employed in various studies. Eggs of (Gallus Gallus) chicken were immersed in an aqueous solution of two sub-lethal concentrations (0.375 and 0.0375mg/L for LCT; 0.05 and 0.005mg/L for IMD) for 30 sec on the fourth day of incubation of chick embryos. Significant reductions of acetylcholinesterase (AChE) activity of brain 18- and 21-day chicks were observed in the groups treated with LCT and IMD dependent on concentrations. There were significant changes (reduction or enhancement) in serum activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) by LCT and IMD at the used concentrations, while non-significant stimulation in the AST/ALT ratio (AAR) was found. In 18th - day embryos, the activities of glutathione S-transferase (GST) and acid phosphatase (ACP) were not significantly changed by LCT but were significantly increased by IMD. Liver alkaline phosphatase (ALP) activity showed no significant change except IMD at 0.05mg/L. However, serum enzyme activity was significantly reduced in all groups. In addition, the tested insecticides caused notable increases in the creatinine and total protein content. The protein profile; proteins separation with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed an increase in four bands that are consistent with the results of the biomarkers level. Findings indicate that even the pesticide's low concentrations are not safe and may lead to severe damage to the embryos and may lead to significant harm or developmental disruption in the embryos.

PPARβ/δ agonist GW0742 mitigates acute liver damage induced by acetaminophen overdose in mice

Liver damage caused by acetaminophen (APAP) overdose remains a worldwide medical problem. New therapeutic medicines for APAP poisoning are needed as the efficacy of the only antidote, N-acetyl-cysteine (NAC), significantly decreases if administered after 8 h of APAP intake and massive APAP overdose remains to induce hepatotoxicity despite the timely administration of NAC. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) possesses versatile roles including regulation of lipid homeostasis and anti-inflammation in the liver. This study aimed to investigate the effects of GW0742, one specific PPARβ/δ agonist, on APAP-caused liver damage in mice. We found that GW0742 (40 mg/kg, i.p.) pretreatment completely blocked the increase of serum aminotransferase activities, hepatocyte necrosis, oxidative stress, and liver inflammation in mice exposed to 300 mg/kg APAP (i.p.). Mechanistically, GW0742 pretreatment significantly suppressed the M1 polarization of liver Kupffer cells and activation of NLRP3 inflammasome. Interestingly, GW0742 remained effective when administered 6 h after APAP exposure, although its efficacy was less pronounced than that administered 6 h before the APAP challenge. Notably, GW0742 exhibited a more profound effect than NAC evidenced by the lower serum alanine transaminase (ALT) level and the improved histopathological manifestation. Furthermore, exposure to APAP for 6 h had resulted in dramatic liver inflammation, while pretreatment with GW0742 prior to APAP exposure did not influence the increase in serum aminotransferase activity and oxidative stress at 2 h after APAP exposure. These results highlight that PPARβ/δ may be a promising therapeutic target for treating APAP-caused acute liver damage probably acting on liver macrophages.

Interventional effect of bone marrow mesenchymal stem cell transplantation with different doses of X-ray irradiation induced hepatic injury in mice

Objective: To investigate the interventional effect of bone marrow mesenchymal stem cell (BMMSC) transplantation with different doses of X-ray irradiation induced hepatic injury in mice. Methods: Eighteen female C57BL/6J mice were randomly divided into 0, 2, and 3 Gy irradiation groups and 0, 2, and 3 Gy transplantation groups. The irradiation group was used as the control and injected with an equal volume of culture medium. The mice in the transplantation group were irradiated with different doses of X-ray irradiation, and BMMSCs were intravenously infused into the bone marrow. The mice were sacrificed for sampling at the end of the 21st day. Mice body weight changes were recorded daily. The changes in the content of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were detected by an automatic blood tester. The morphological changes in mice liver tissues were observed by hematoxylin-eosin staining. The serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by a biochemical analyzer. The reduced glutathione contents in liver tissue were detected by the microplate method. The malondialdehyde content in liver tissue was detected by thiobarbituric acid. The content of total superoxide dismutase (T-SOD) in liver tissue was detected by the hydroxylamine method. The expression of the F4/80 protein in liver tissue was detected by the immunohistochemistry method. The protein expression of nuclear transcription factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in liver tissue was determined by the western blotting method. The mRNA expression of NLRP3, IL-6, and Nrf2 in liver tissue was detected by a real-time quantitative polymerase chain reaction. The multiple-group comparisons were analyzed by factorial analysis of variance. The inter-group comparisons were analyzed by the LSD method for statistical analysis. Results: The contents of peripheral blood lymphocytes, erythrocytes, platelets, and hemoglobin were significantly decreased in the 3 Gy irradiation group than the 0 Gy irradiation group (P<0.05), while the activities of serum ALT and AST were significantly increased (P<0.05). The malondialdehyde content, F4/80 protein expression level, nucleotide-binding domain and leucine-rich repeats, nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), and interleukin 6 mRNA expression levels were significantly increased in liver tissue, while the contents of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly decreased (P<0.05). The contents of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were significantly increased in the 3 Gy transplantation group than the 3 Gy irradiation group (P<0.05), while the activities of serum ALT and AST were significantly decreased (P<0.05). The malondialdehyde content, F4/80 protein expression level, NLRP3 and interleukin-6 mRNA expression levels in liver tissue were significantly decreased (P<0.05), while the content of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly increased (P<0.05). Conclusion: X-ray irradiation at a dose of 3 Gy can induce liver oxidative damage in mice. BMMSC transplantation can improve X-ray irradiation-induced liver oxidative damage in mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1 pathway.

Inducible global knockout of surfeit locus protein 4 in adult mice results in hypolipidemia, intestinal lipid accumulation, liver injury, and increased mortality

Surfeit locus protein 4 (SURF4) acts as a cargo receptor to mediate endoplasmic reticulum export of various cargos. We have shown that SURF4 is essential for secretion of hepatic very low-density lipoprotein and intestinal chylomicron. Knockdown of hepatic Surf4 also significantly reduces the development of atherosclerosis and liver fibrosis without causing overt liver damage. However, constitutive global Surf4 knockout results in embryonic lethality. To further understand the physiological role of SURF4, we generated tamoxifen-inducible global Surf4 knockout mice. We found that conditional knockout of Surf4 in adult mice (Surf4ig-ko) significantly reduced mouse body weight. Male and female Surf4ig-ko mice died approximately 30 and 50 days after tamoxifen administration, respectively. Triglyceride secretion and serum levels of total cholesterol, triglycerides, free fatty acids, apolipoprotein B-100, and apolipoprotein B-48 were significantly reduced in Surf4ig-ko mice compared with Surf4flox mice. Proteomics analysis of mouse serum samples revealed 308 proteins with significantly altered expression in Surf4ig-ko mice that have unique functions and are involved in various biological processes. In addition, Surf4ig-ko mice exhibited lipid accumulation in the intestine but not in the liver. However, in Surf4ig-ko mice, liver weight was significantly reduced, and serum transaminase activity was significantly increased, indicating liver damage. Therefore, SURF4 is essential for survival in adult mice, suggesting that the therapeutic use of SURF4 requires precise tissue/cell type-specific targeting.

Docosahexaenoic acid alleviated liver lipid deposition and health damage induced by cholesterol accumulation in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂)

Cholesterol accumulation can be a critical pathological marker and, while, the cholesterol-lowering potential of docosahexaenoic acid (DHA) has been documented extensively in mammals, its effects in fish are unclear. The present study investigated the adverse effects of cholesterol accumulation on liver health, and evaluated DHA as a potential cholesterol-lowering agent to mitigate liver damage induced by high cholesterol (HC) intake in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). Grouper were fed either a control diet or an HC (1.6 %) diet supplemented with varying levels of DHA (0, 0.5, 1, 2 %) for eight weeks. The HC diet significantly increased condition factor (CF), mesenteric fat index (MFI), and lipid, cholesterol and triglyceride accumulation in liver. Supplementing the HC diet with 0.5 % DHA significantly reduced CF, MFI and liver lipid contents. Moreover, HC intake increased aspartate transaminase (AST) and alanine transaminase (ALT) activities in serum, and malondialdehyde (MDA) content and the expression of gene related to inflammatory responses and apoptosis in liver. In addition, HC intake significantly reduced mitochondrial biogenesis and total antioxidant capacity in liver. However, supplementing the HC diet with 0.5 % DHA significantly decreased liver cholesterol accumulation by inhibiting cholesterol synthesis and promoting cholesterol efflux, and significantly reduced liver triglyceride content by inhibiting the expression of genes associated with lipogenesis and lipid droplet formation. Furthermore, supplementation of the HC diet with 0.5 % DHA significantly reduced the activities of ALT and AST in serum, and MDA content and the expression of genes associated with inflammation, apoptosis and antioxidation in liver, and enhanced liver mitochondrial biogenesis. Overall, the results indicated that DHA supplementation mitigated liver cholesterol accumulation by inhibiting cholesterol synthesis and promoting cholesterol efflux, and enhanced mitochondrial function, boosted antioxidant capacity, and reduced inflammation in liver of grouper fed the HC diet, ultimately alleviating liver damage caused by cholesterol accumulation. The present study elucidated the detrimental effects of cholesterol accumulation on liver health in aquatic animals and proposed DHA as a potential intervention for mitigating health issues associated with cholesterol overload.

Liver-directed AAV gene therapy normalizes disease symptoms and provides cross-correction in a model of lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency (LAL-D) is caused by mutations in the LIPA gene, which encodes the lysosomal enzyme that hydrolyzes triglycerides and cholesteryl esters to free fatty acids and free cholesterol. The objective of this study was to develop a curative single-treatment therapy for LAL-D using adeno-associated virus (AAV). Treatment at both early (1-2 days) and late (8 week) timepoints with rscAAVrh74.LP1.LIPA, a liver-directed AAV gene therapy, normalized many disease measures in Lipa-/- mice when measured at 24 weeks of age, including hepatosplenomegaly, serum transaminase activity, organ triglyceride and cholesterol levels, and biomarkers of liver inflammation and fibrosis. For most measures, liver-directed therapy was superior to therapy utilizing a constitutive tissue expression approach. rscAAVrh74.LP1.LIPA treatment elevated LAL enzyme activity above wild-type levels in all tissues tested, including liver, spleen, intestine, muscle, and brain, and treatment elicited minimal serum antibody responses to transgenic protein. AAV treatment at 8 weeks of age with 1x1013 vg/kg extended survival significantly, with all AAV-treated mice surviving beyond the maximal lifespan of untreated Lipa-/- mice. These results show that this liver-directed LIPA gene therapy has the potential to be a transformative treatment for LAL-D.

Hepatocyte apoptosis is triggered by hepatic inflammation in common carp acutely exposed to microcystin-LR or chronically exposed to Microcystis

Cyanobacterial blooms pose a serious threat to the survival of fish because of the hepatotoxicity of microcystins produced by toxic cyanobacteria such as Microcystis. Many studies have investigated the hepatotoxicity of microcystins in common carp, a freshwater fish distributed worldwide, but the hepatotoxicity mechanism has not been fully clarified. The present study aimed to investigate the mechanism underlying the hepatic inflammatory response and hepatocyte apoptosis induced by acute microcystin-LR exposure via intraperitoneal injection (71 μg/kg and 119 μg/kg) or gavage (357.08 μg/kg) and chronic exposure to toxic Microcystis blooms. The results of acute exposure revealed that microcystin-LR caused an increase in serum transaminase activity and increased the levels of inflammatory factors and inflammatory mediators, inducing a significant inflammatory response in the liver of common carp. Moreover, biochemical detection revealed that hepatocyte apoptosis occurred in the fish. Moreover, chronic toxic Microcystis exposure also caused hepatic inflammation and subsequent apoptosis mediated by the tumour necrosis factor-α (TNF-α) pathway and the mitochondrial pathway similar to acute exposure. Therefore, our study suggests that the inflammatory response induced by microcystin-LR exacerbates apoptosis, likely mediated by TNF-α. In summary, both acute microcystin-LR exposure and chronic toxic Microcystis exposure can cause inflammation in the liver of common carp, which subsequently triggers hepatocyte apoptosis mediated by the TNF-α pathway and the mitochondrial pathway. This study helps elucidate the mechanism of liver damage induced by cyanobacterial blooms in natural water.

Indicators of functional state of liver, blood lipid spectrum in patients with steatotic liver disease associated with metabolic dysfunction: modern approaches to complex treatment. Review

Objective — to study the dynamics of indicators of the functional state of the liver, the lipid spectrum of the blood, to evaluate the cardiovascular risk according to SCORE‑2 (Systematic Coronary Risk Estimation 2) scale under the influence of complex pathogenetic treatment of the detected disorders in patients with steatotic liver disease associated with metabolic dysfunction (SLDMD) in combination with obesity. Materials and methods. 46 outpatients with a diagnosis SLDMD were examined: 29 (63.1%) men and 17 (36.9%) women aged 32—55 years. The patients were divided into two groups. The main group included 19 (41.3%) persons who received atorvastatin: 20 mg/day for 90 days. The comparison group consisted of 27 (58.7%) patients who were prescribed ursodeoxycholic acid preparations in combination with atorvastatin: 250 mg (15 mg/kg of body weight) for 90 days. The control group consisted of 12 healthy persons of the appropriate age. The anthropometric criterion of obesity was the Quetelet index. Phenotypic variant of obesity was determined by the ratio of waist circumference/hip circumference (WC/HC). Among the patients of the main group, there were 9 (47.4%) persons with I degree of obesity ((32.6±2.2) kg/m2), 6 (31.5%) persons with II degree ( 35.8±3.6 kg/m2), and 4 (21.1%) persons with III degree (40.0±2.1kg/m2), in the comparison group there were 17 (62.9%), 6 (22.3%) and 4 (14.8%) patients, respectively. All patients received a differentiated diet with the calculation of the energy value, the quota of protein (1.4—1.6 g), fat (1.2—1.4 g), carbohydrates (2—3 g) per 1 kg of ideal body weight and dosed physical activity. For assessing the indicators of the functional state of the disease we determined: the level of general bilirubin and its fractions (direct and indirect), activity of serum aminotransferases, alkaline phosphatase, total cholesterol content in the blood serum, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol, very‑low‑density lipoprotein cholesterol, triglycerides. Results. In the majority of patients with SLDMD, a statistically significant (p &lt;0.05) increase in the level of direct bilirubin in the blood, the activity of hepatic transaminases, alkaline phosphatase, and changes in the lipid spectrum of the blood were detected. According to the body mass index (BMI) most of the examined patients had visceral obesity. After the course of the combined therapy positive dynamics was marked in biochemical indices of the blood (p &lt;0.05): decrease of the direct bilirubin level, hepatic transaminases, blood phosphatase. The lipid spectrum of the blood was close to normal (p &lt;0.05). The addition of ursodeoxycholic acid to statin therapy contributes to a statistically significant reduction in total cardiovascular risk according to the SCORE 2 scale compared with atorvastatin monotherapy. All patients were recommended to continue the course of treatment (combination of atorvastatin and ursodeoxycholic acid) for 2 to 3 months. Conclusions. The use of a combination of statin and ursodeoxycholic acid in the treatment of patients with SLDMD and obesity helps to normalise the functional state of the liver and blood lipid parameters, reduce the degree of overall cardiovascular risk, and achieve clinical and biochemical remission of the pathological process in the liver.

Steatotic liver disease associated with 2,4-dienoyl-CoA reductase 1 deficiency

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is considered multifactorial with a number of predisposing gene polymorphisms known.MethodsThe occurrence of MASLD in 7 and 10 year old siblings, one without classical risk factors and one with type 2 diabetes suggested a monogenic etiology and prompted next-generation sequencing. Exome sequencing was performed in the proband, both parents and both siblings. The impact of a likely disease-causing DNA variant was assessed on the transcript and protein level.ResultsTwo siblings have hepatomegaly, elevated serum transaminase activity, and steatosis and harbor a homozygous DECR1 splice-site variant, c.330+3A>T. The variant caused DECR1 transcript decay. Immunostaining demonstrated lack of DECR1 in patient liver.ConclusionsThese patients may represent the first individuals with DECR1 deficiency, then defining within MASLD an autosomal-recessive entity, well corresponding to the reported steatotic liver disease in Decr1 knockout mice. DECR1 may need to be considered in the genetic work-up of MASLD.

Effects of High-Intensity Training on Complete Blood Count, Iron Metabolism, Lipid Profile, Liver, and Kidney Function Tests of Professional Water Polo Players.

Our goal was to examine the effect of high-intensity physical activity on changes in the lipid profile, complete blood count (CBC), iron metabolism, and kidney and liver function tests of professional water polo players. This study included twenty professional male water polo players. Blood sampling was carried out at the beginning of the season and during periods of high-intensity training. CBCs were determined with a Siemens Advia 2120i hematology analyzer. A Beckman CoulterAU680 chemistry analyzer was used to determine the serum concentrations/activities of lipid profiles and liver and kidney function test analytes. The lipid athlete scores were also determined. The mean corpuscular volume (p = 0.006), platelet count (p = 0.008), and mean platelet volume (p < 0.001) significantly decreased during the high-intensity period, compared with the beginning of the season. The total iron-binding capacity increased (p = 0.001), and ferritin concentrations significantly declined (p = 0.017). The lipid profiles revealed a significant difference between phases, with slight increases in serum total (p = 0.025) and LDL cholesterol (p = 0.002) levels and a decrease in triglyceride concentrations (p = 0.040) in the high-intensity period. During the high-intensity period, the liver and kidney function tests showed a substantial positive effect on lactate dehydrogenase levels (p < 0.001), aspartate aminotransferase (p = 0.028) serum activity, and total protein concentrations (p = 0.033), compared with the beginning of the season. Water polo players might exhibit a decrease in some CBC parameters, an increase in LDL cholesterol, and a decrease in liver function biomarkers due to intense training at the peak of the competitive season. Kidney function biomarkers remain unchanged.

Blood research of Simmental breed animals in the Carpathian region

Physiological and biochemical blood parameters in Simmental heifers in postnatal ontogenesis of different types of constitution are presented. The physiological and selection index was calculated on the basis of digital indicators of the intensity of transamination enzymes and body weight of heifers in the corresponding periods of growth. It is shown that at the age of 6 months it is possible to assess the young, in this case heifers, by the type of constitution. The number of erythrocytes in the blood of heifers at 6, 12, 18 months old in the experimental group was higher than that of the control ones by 4.25; 9.91; 9.82 %, respectively. On average, over the entire period of rearing, the animals of the experimental group exceeded the control counterparts by 7.92 %. In terms of hemoglobin content in the blood, the experimental heifers at the ages of 6, 12, 18 months exceeded the control counterparts by 8.20; 10.83; 10.90 %, respectively. On average, over the entire period of rearing, the animals of the experimental group exceeded the control counterparts by 7.64 %. In terms of total protein content in the blood serum, the heifers at the ages of 6, 12, 18 months old in the experimental group exceeded the control counterparts by 7.47; 15.23; 8.64 %. On average, over the entire growing period, the animals of the experimental group outnumbered the control counterparts by 8.09 %. Another important indicator, which also characterizes protein metabolism in the animal body, is the activity of aminotransferases in the blood serum. In terms of AST activity in the blood serum, on average over the entire period of growing animals, the experimental group exceeded the control group by 11.78 %. A similar pattern was found in terms of ALT activity in the blood serum. Thus, the heifers of the experimental group in terms of ALT activity in the blood serum at 6, 12, 18 months old exceeded the control peers by 4.72; 8.13; 8.01; 10.28 %, respectively. In terms of the content of total sulfhydryl groups in the blood of heifers of the experimental group at 6, 12, 18 months, they were superior to the control analogues by 10.85; 27.50; 23.44; 18.01 %, respectively. In terms of the content of residual SH-groups in the blood of animals of the experimental group in postnatal ontogenesis, they were superior to the control analogues by 24.34 %. Experimental heifers in terms of total glutathione content at the age periods of 6, 12, 18 months old exceeded control counterparts by 8.38; 20.25; 7.44; 5.48 %, respectively. A similar pattern was observed in terms of reduced glutathione content in the blood of experimental animals. Thus, in terms of reduced glutathione content in the blood of individuals of the experimental group for the entire period of cultivation, they exceeded control peers by an average of 9.56 %.

Вплив комплексу біопротекторів на динаміку активності амінотрансфераз у сироватці крові за умов окремої та одночасної дії свинцю і фтору (експериментальні дослідження)

Lead and fluoride enter the human body individually and simultaneously through water, food, and air, disrupting metabolic processes in liver tissue. The sequential application of a bioprotective complex that reduce the negative effects of lead and fluoride has been insufficiently studied. The aim of the study is to investigate the changes over time in the activity of alanine aminotransferase and aspartate aminotransferase in the blood serum of laboratory animals under prolonged separate and simultaneous exposure to lead and fluoride, without application of bioprotective agents and during the sequential addition of pectin, pectin with calcium, and a complex of pectin, calcium, and antioxidants to the standard animal diet. Materials and Methods. Four clinical trial series were conducted on white rats, each following an orthogonal design 22. Aqueous solutions of Pb(NO3)2 and NaF were administered orally separately and simultaneously over 30 days: in the first series without bioprotective agents, in the second with pectin, in the third with pectin and calcium, and in the fourth with a complex of pectin, calcium, and antioxidants – C, E, and β-carotene vitamins, and selenium. The activity of alanine and aspartate aminotransferases was measured in blood serum on days 3, 15, and 30 in the first and second series of experiments, and on day 30 in the third and fourth series. Results. Separate and simultaneous oral administration of lead and fluoride to white rats leads to increased activity of alanine and aspartate aminotransferases in blood serum. The maximum changes were observed at the end of the experiment. The protective role of pectin alone under long-term fluoride expos ure and simultaneous exposure to lead and fluoride was not sufficiently effective. Concurrent intake of calcium and pectin significantly reduced the increase in transaminase activity, indicating an improvement in the metabolic and functional state of the liver. The application of the bioprotective complex restored the aminotransferase activity in blood serum. Conclusions. The complex of pectin with calcium and antioxidants can be considered an optimal means of correcting aminotransferase activity in blood serum under prolonged separate and simultaneous exposure to lead and fluoride.

Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs.

S-adenosylmethionine (SAM) is the main methyl group donor and has antioxidant potential. In this study, preventive and regressive potential of SAM were investigated in high fat/high cholesterol (HFHC) diet-induced non-alcoholic fatty liver disease (NAFLD) in guinea pigs. They were injected with SAM (50 mg/kg, i.p.) for 6 weeks along with HFHC diet or 4 weeks after HFHC diet. Serum transaminase activities, total cholesterol (TC), triglyceride (TG), cytochrome p450-2E1 (CYP2E1) and hydroxyproline (Hyp) levels, prooxidative and antioxidative parameters, protein expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) together with histopathological changes were examined in the liver. SAM treatment diminished HFHC diet-induced increases in serum transaminase activities and hepatic TC, TG, CYP2E1, Hyp, α-SMA and TGF-β1 expressions and ameliorated prooxidant-antioxidant balance. Histopathological scores for hepatic steatosis, inflammation, and fibrosis were decreased by SAM treatment. Increases in TC, diene conjugate levels, and lipid vacuoles within the tunica media of the aorta were reduced in HFHC-fed animals treated with SAM. These protective effects were also detected in the regression period of HFHC-guinea pigs due to SAM. In conclusion, SAM treatment was found to be effective in prevention and regression of HFHC-induced hepatic and aortic lesions together with decreases in oxidative stress in guinea pigs with NAFLD.

Epicatechin ameliorates glucose intolerance and hepatotoxicity in sodium arsenite-treated mice

Arsenic is a metalloid found in the environment that causes toxic effects in different organs, mainly the liver. This study aimed to investigate the protective effects of epicatechin (EC), a natural flavonol, on glucose intolerance (GI) and liver toxicity caused by sodium arsenite (SA) in mice. Our findings showed that SA exposure led to the development of GI. Liver tissue damage and decreased pancreatic Langerhans islet size were also observed in this study. Mice exposed to SA exhibited hepatic oxidative damage, indicated by reduced antioxidant markers (such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione), along with elevated levels of thiobarbituric acid reactive substances. SA administration elevated the serum activities of liver enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Furthermore, notable increases in the levels of inflammatory and apoptotic markers (Toll-like receptor 4, nuclear factor-kappa B, tumor necrosis factor-α, nitric oxide, B-cell lymphoma-2, and cysteine aspartate-specific protease-3) were observed in the liver. Treatment of SA-exposed mice with EC considerably reversed these biochemical and histological changes. This study demonstrated the beneficial effects of EC in ameliorating SA-induced hyperglycemia and hepatotoxicity due to its ability to enhance the antioxidant system by modulating inflammation and apoptosis.

Profile of plasma microRNAs as a potential biomarker of Wilson’s disease

BackgroundWilson’s disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs.MethodsWe conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b−/− mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age.ResultsIn patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b−/− mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream.ConclusionsThe upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD.

Hydroxysafflor yellow A exerts anti-fibrotic and anti-angiogenic effects through miR-29a-3p/PDGFRB axis in liver fibrosis

BackgroundLiver fibrosis is a prevalent pathological process in chronic liver diseases characterized by excessive extracellular matrix (ECM) deposition and abnormal angiogenesis. Notably, hepatic stellate cells (HSCs) are the primary source of ECM. Activated HSCs not only secrete numerous pro-fibrotic cytokines but also are endowed with a pro-angiogenic phenotype to promote pathological angiogenesis. Therefore, targeted modulation of HSCs has emerged as a pivotal strategy for addressing liver fibrosis. Hydroxysafflor yellow A (HSYA) is a homology of medicine and food colourant with good pharmacological activity. However, the precise mechanisms of HSYA against liver fibrosis remain unclear. PurposeThe objective of this study was to elucidate the impact of HSYA on liver fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo studies. MethodsThe efficacy and mechanisms of HSYA on TGF-β1-induced HSCs and VEGFA-induced endothelial cells were investigated by MTT assay, EdU cell proliferation assay, cell scratch assay, Elisa assay, immunofluorescence assay, molecular docking, cell transfection assay, western blot analysis and RT-qPCR analysis. In CCl4-induced liver fibrosis mice model, H&E, Masson, and Sirius red staining were used to observe histopathology. Serum transaminase activity and liver biochemical indexes were tested by biochemical kit. Immunohistochemical, fluorescence in situ hybridization (FISH), western blot analysis and RT-qPCR analysis were implemented to determine the mechanism of HSYA in vivo. ResultsHerein, our findings confirmed that HSYA inhibited the proliferation, migration and activation of HSCs, as evidenced by a reduction in cell viability, relative migration rate, EdU staining intensity, and pro-fibrotic mRNAs and proteins expression in vitro. Mechanistically, HSYA played an anti-fibrotic and anti-angiogenic role by partially silencing PDGFRB in activated HSCs, thereby disrupting PDGFRB/MEK/ERK signal transduction and inhibiting the expression of HIF-1α, VEGFA and VEGFR2 proteins. Importantly, PDGFRB was a target gene of miR-29a-3p. Treatment with HSYA reversed the down-regulation of miR-29a-3p and antagonized PDGFRB signaling pathway in TGF-β1-induced HSCs transfected with miR-29a-3p inhibitor. Consistent with our in vitro study, HSYA exhibited a good hepatoprotective effect in CCl4-induced liver fibrosis mice by reducing serum ALT and AST levels, decreasing the contents of four fibrosis indicators (HA, PIIIP, ColIV and LN) and hydroxyproline, and inhibiting the TGF-β1/TGFBR signaling pathway. In terms of mechanisms, HSYA alleviated pathological angiogenesis in fibrotic liver by deactivating PDGFRB signaling pathway and impairing the positive expression of CD31. Subsequently, FISH results further corroborated HSYA affected the activation of HSCs and angiogenesis achieved by the concurrent upregulation of miR-29a-3p and downregulation of α-SMA and VEGFA. Additionally, treatment with HSYA also forged a link between HSCs and endothelial cells, as supported by inhibiting the aberrant proliferation of endothelial cells. ConclusionFundamentally, the current study has illustrated that HSYA ameliorates liver fibrosis by repressing HSCs-mediated pro-fibrotic and pro-angiogenic processes, which is contingent upon the regulatory effect of HSYA on the miR-29a-3p/PDGFRB axis. These findings provide compelling evidence bolstering the potential of HSYA as a therapeutic agent in liver fibrosis.

Dietary saccharin sodium supplementation improves the production performance of dairy goats without residue in milk in summer

The purpose of this study was to investigate the effects of dietary saccharin sodium supplementation on production performance, serum biochemical indicators, and rumen fermentation of dairy goats in summer. Twelve Guanzhong dairy goats with similar body weight, days in milk, and milk yield were randomly divided into two dietary treatments: (1) CON: basal diet; (2) SS: basal diet + 150 mg/kg saccharin sodium on the basis of dry matter. The experiment lasted 35 d, including 7 d for adaptation and 28 d for dietary treatments, sampling and data collection. Each dairy goat was housed individually in a clean separate pen with ad libitum access to diet and water. The goats fed SS diet had increased dry matter intake (DMI; P = 0.037), 4% fat corrected milk yield (P = 0.049), energy corrected milk yield (P = 0.037), milk protein yield (P = 0.031), and total solids yield (P = 0.036). Serum activity of aspartate aminotransferase (P = 0.047) and concentrations of 70-kDa heat shock protein (P = 0.090), malondialdehyde (P = 0.092), and total protein (P = 0.057) were lower in goats fed SS diet than those fed CON diet. Supplementation of saccharin sodium tended to increase activity of glutathione peroxidase in serum (P = 0.079). The concentrations of rumen total volatile fatty acid (P = 0.042) and butyrate (P = 0.038) were increased by saccharin sodium supplementation. Dietary supplementation of saccharin sodium increased the relative abundance of Lachnobacterium (P = 0.022), Pseudoramibacter (P = 0.022), Shuttleworthia (P = 0.025), and Syntrophococcus (P = 0.037), but reduced the relative abundance of Prevotella_1 (P = 0.037) and Lachnospiraceae_UCG_008 (P = 0.037) in rumen. Saccharin sodium was observed in feces and urine of goats fed diet supplemented with saccharin sodium, but saccharin sodium was undetectable in the milk of goats receiving SS diet. In conclusion, administration of saccharin sodium was effective in increasing fat and energy corrected milk yield by increasing DMI and improving rumen fermentation and antioxidant capacity of dairy goats in summer. In addition, saccharin sodium residue was undetectable in the milk.

Effects of yellow mealworm (Tenebrio molitor) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome in broiler chickens

The goal of this study was to evaluate the effects of Tenebrio molitor (TM) larvae meal on the growth performance, serum biochemical parameters and caecal metabolome of broiler chickens. A total of 600 1-d-old male Liangfenghua broilers were randomly assigned to five equal groups with 5 replicates and 24 birds in each replicate. The dietary treatments were as follows: the control group (TM0 group) was fed a basal diet, and the experimental groups were fed experimental diets in which 3% (TM3 group), 5% (TM5 group), 7% (TM7 group) and 9% (TM9 group) TM larvae meal included in the basal diet, respectively. The feeding period was 70 d. The results showed that body weight (BW) and average daily gain (ADG) significantly increased (p < 0.05) in response to dietary 3% TM larvae meal supplementation at the age of 70 d. Serum concentrations of triglyceride (TG) and serum activity of aspartate aminotransferase (AST) decreased (p < 0.05) in 3% TM larvae meal-fed broilers. UHPLC-MS/MS-based metabolomics analysis revealed that a total of 55 significantly different metabolites were obtained in the caecal contents of dietary TM larvae meal supplemented broilers. The relative contents of 28 metabolites such as trans-4-hydroxy-L-proline, thymine and retinoic acid were significantly up-regulated (FC > 1.5) and the relative contents of 27 metabolites like prostaglandin F2α, glucocorticoids and prostaglandin E2 were significantly down-regulated (FC < 0.667) in the TM3 group. The main altered pathways were clustered into arachidonic acid metabolism, primary bile acid metabolism and propionic acid metabolism. In conclusion, the results indicated that supplementation of 3% TM larvae meal can improve growth performance, reduce the activity of serum AST and the content of TG, and regulation of the pathways of lipid, amino acid, and sugar metabolism in the caecum of broilers by improving nutrient digestion and absorption.

Exposure to Benzo(a)pyrene Enhances Acetaminophen-Induced Liver Injury in Mice at Non-Hepatotoxic Doses

Acetaminophen (APAP) is a widely used analgesic, especially for children. Its primary mechanism involves inhibiting cyclooxygenase enzymes and activating the endocannabinoid and TRPV1 systems. Though its toxicity is low, it can harm the liver in a dose-dependent manner. Low APAP doses can also increase pollutant-induced liver damage. Little is known about interactions between APAP and benzo[a]pyrene (B[a]P). This study aimed to assess if co-exposure to non-hepatotoxic doses of B[a]P and APAP causes liver injury in mice, exploring the underlying mechanisms. Female ICR mice received 50 mg/kg B[a]P or a vehicle for three days, followed by 200 mg/kg APAP or a vehicle. Liver injury was assessed through histopathological examination, serum transaminase activity, and gene expression analysis. In the B[a]P/APAP group, several histology changes were observed, including ballooning injury, steatosis, necrosis, inflammation, and apoptosis. Transaminase levels correlated with histopathological scores, and there was an increase in hepatic cytochrome P450 family 1 subfamily a member 1 (Cyp1a1) mRNA levels and a decrease in aryl hydrocarbon receptor (Ahr), cytochrome P450 family 2 subfamily e polypeptide 1 (Cyp2e1), superoxide dismutase 1 (Sod1), peroxisome proliferator activated receptor gamma (Ppar-γ), and caspase 3 (Casp3). This suggests that prior exposure to B[a]P makes mice more susceptible to APAP-induced liver injury, involving changes in gene expression related to metabolism, redox balance, and cell proliferation. Therefore, using therapeutic APAP doses after exposure to B[a]P could lead to liver injury.