Serum Transaminase Activities Research Articles

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.

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 regulation of HSCs has emerged as a critical 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 the modulation of tissue fibrosis and pathological angiogenesis, as well as the underlying mechanisms in vitro and in vivo. 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 HIF-1α, VEGFA and VEGFR2 protein expression. 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+miR-29a-3p inhibitor-induced HSCs. 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, PC-III, 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, blood 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 in heat-stressed dairy goats. In addition, saccharin sodium residue was undetectable in the milk.

Expression of hepatic genes involved in bile acid metabolism in dairy cows with fatty liver

Bile acids are cholesterol-derived molecules that are primarily produced in the liver. In nonruminants with fatty liver, overproduction of bile acids is associated with liver injury. During the transition period, fatty liver is a metabolic disorder that can affect up to 50% of high-producing dairy cows. The purpose of this study was to provide a comprehensive evaluation on hepatic bile acid metabolism in dairy cows with fatty liver by assessing expression changes of genes involved in bile acid synthesis, export and uptake. The serum activities of aspartate aminotransferase, alanine aminotransferase and glutamate dehydrogenase and concentration of total bile acids were all greater, whereas serum concentration of total cholesterol was lower in cows with fatty liver than in healthy cows. Content of total bile acids was higher but total cholesterol was slightly lower in liver tissues from fatty liver cows than from healthy cows. The hepatic mRNA abundance of cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 7 (HSD3B7) and sterol 12α-hydroxylase (CYP8B1), enzymes involved in the classic pathway of bile acid synthesis, was higher in fatty liver cows than in healthy cows. Compared with healthy cows, the hepatic mRNA abundance of alternative bile acid synthesis pathway-related genes sterol 27-hydroxylase (CYP27A1) and oxysterol 7α-hydroxylase (CYP7B1) did not differ in cows with fatty liver. The protein and mRNA abundance of bile acid transporter bile salt efflux pump (BSEP) were lower in the liver of dairy cow with fatty liver. Compared with healthy cows, the hepatic mRNA abundance of bile acid transporters solute carrier family 51 subunit α (SLC51A), ATP binding cassette subfamily C member 1 (ABCC1) and 3 (ABCC3) was greater in cows with fatty liver, whereas the solute carrier family 51 subunit β (SLC51B) did not differ. The expression of genes involved in bile acid uptake, including solute carrier family 10 member 1 (NTCP), solute carrier organic anion transporter family member 1A2 (SLCO1A2) and 2B1 (SLCO2B1) was upregulated in dairy cows with fatty liver. Furthermore, the hepatic protein and mRNA abundance of bile acid metabolism regulators farnesoid X receptor (FXR) and small heterodimer partner (SHP) were lower in cows with fatty liver than in healthy cows. Overall, these data suggest that inhibition of FXR signaling pathway may lead to the increased bile acid synthesis and uptake and decreased secretion of bile acids from hepatocytes to the bile, which elevates hepatic bile acids content in dairy cows with fatty liver. As the hepatotoxicity of bile acids has been demonstrated on nonruminant hepatocytes, it is likely that the liver injury is induced by increased hepatic bile acids content in dairy cows with fatty liver.

Short-term dietary teprenone improved thermal tolerance and mitigated liver damage caused by heat stress in juvenile largemouth bass (Micropterus salmoides)

Heat stress seriously threatens fish survival and health, demanding immediate attention. Teprenone is a gastric mucosal protective agent that can induce heat shock protein expression. This research investigated the effects of teprenone on largemouth bass (Micropterus salmoides) subjected to heat stress. Juvenile fish were assigned to different groups: group C (control group, 0 mg teprenone/kg diet), T0, T200, T400, and T800 (0, 200, 400, and 800 mg teprenone/kg diet, respectively), which were fed for 3 days, followed by a day without the diet. All groups except group C were subjected to acute heat stress (from 24 °C to 35 °C at 1 °C per hour and then maintained at 35 °C for 3 h). The results were as follows: The critical thermal maxima were significantly higher in the T200, T400, and T800 groups compared with the T0 group (P < 0.05). Heat stress caused severe damage to the tissue morphology of the liver, while teprenone significantly reduced this injury (P < 0.05). Serum cortisol concentration decreased gradually as teprenone concentration increased, and the lowest concentration was observed in the T800 group (P < 0.05). Compared with the T0 group, the serum activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase were significantly lower in the T200, T400, and T800 groups (P < 0.05). The liver activities of catalase, total superoxide dismutase, and peroxidase were significantly higher in the T200 group than in the T0 group (P < 0.05). Transcript levels of the heat shock proteins (hsp90, hsp70, hspa5, and hsf1) and caspase family (caspase3 and caspase9) in the liver of the T200 group were significantly higher than those of the T0 group (P < 0.05). Western blot results showed that HSP70 and HSPA5 in the liver were significantly upregulated in the T200 group compared with the T0 group (P < 0.05). In summary, dietary teprenone improved thermal tolerance, alleviated heat stress damage in the liver, enhanced antioxidant capacity, and upregulated heat shock proteins in juvenile largemouth bass. This study offers theoretical support for applying teprenone in aquaculture to reduce financial losses caused by abiotic factors.

Effect of per os administration of fucoxanthin alcoholic and oil extracts to Balb/c mice on biochemical parameters and serum cytokine level

Microalgae are a source of various biologically active substances, including carotenoids. One of the carotenoids of diatom microalgae is fucoxanthin, which has antioxidant, antimicrobial, antitumour and anti-inflammatory properties that can be used in the treatment of a wide range of human and animal pathologies. The aim of the study was to investigate the effect of alcohol and oil extract of fucoxanthin on biochemical parameters and levels of serum cytokines in mice during intragastric administration. Material and methods. Fucoxanthin extracts from the microalga Nanofrustulum shiloi were used. Mice of Balb/c strain were intragastrically administrated with 0.5 ml of oil (500 μg/ml) or alcoholic extract of fucoxanthin (187.5 μg/ml), mice in the comparison group were given 0.5 ml of olive oil or 45% ethyl alcohol once a day within 5 days. On the 8th day, blood serum was obtained and the level of albumin, triglycerides, cholesterol, low (LDL) and high density lipoproteins (HDL), urea, uric acid, creatinine, aspartate (AST) and alanine aminotransferases (ALT), lactate, stable nitric oxide (NO) metabolites (nitrites), cytokines (IL-1β, IL-6, IL-10, TNF-α, IFN-γ) was determined using ELISA with photometric detection. Results and discussion. In the comparison group, ethyl alcohol promoted an increase in serum triglyceride, cholesterol, LDL, HDL, ALT, AST, nitrite, IL-10, IFN-γ and TNF-α content compared to intact animals. Fucoxanthin alcoholic extract administration increased the level of LDL, HDL, uric acid, TNF-α and decreased albumin, cholesterol, uric acid, creatinine, ALT, AST, IL-6 content compared to control. The olive oil group showed a decrease in serum triglycerides, cholesterol, urea, uric acid, ALT and AST content but an increase in LDL, HDL, nitrite level compared to the control. Administration of fucoxanthin oil extract to animals decreased albumin, triglycerides, cholesterol, HDL, uric acid, ALT, AST, lactate, IL-6, IL-10 compared to control. Conclusions. Thus, it was discovered that fucoxanthin in Balb/c mice contributes to a decrease in hepatic synthetic function, as evidenced by the change in the concentration of albumin, triglycerides, uric acid), influences energy metabolism (creatinine, lactate), cell membrane stability (cholesterol, LDL, HDL), serum transaminase activity, pro- and anti-inflammatory cytokines content.

Antagonizing Activin A/p15INK4b Signaling as Therapeutic Strategy for Liver Disease.

Activin A is involved in the pathogenesis of human liver diseases, but its therapeutic targeting is not fully explored. Here, we tested the effect of novel, highly specific small-molecule-based activin A antagonists (NUCC-474/555) in improving liver regeneration following partial hepatectomy and halting fibrosis progression in models of chronic liver diseases (CLDs). Cell toxicity of antagonists was determined in rat hepatocytes and Huh-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Hepatocytes and hepatic stellate cells (HSCs) were treated with activin A and NUCC-555 and analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry. Partial hepatectomized Fisher (F)344 rats were treated with NUCC-555, and bromodeoxyuridine (BrdU) incorporation was determined at 18/24/36/120/240 h. NUCC-555 was administered into thioacetamide- or carbon tetrachloride-treated F344 rats or C57BL/6 mice, and the fibrosis progression was studied. NUCC-474 showed higher cytotoxicity in cultured hepatic cells; therefore, NUCC-555 was used in subsequent studies. Activin A-stimulated overexpression of cell cycle-/senescence-related genes (e.g., p15INK4b, DEC1, Glb1) was near-completely reversed by NUCC-555 in hepatocytes. Activin A-mediated HSC activation was blocked by NUCC-555. In partial hepatectomized rats, antagonizing activin A signaling resulted in a 1.9-fold and 2.3-fold increase in BrdU+ cells at 18 and 24 h, respectively. Administration of NUCC-555 in rats and mice with progressing fibrosis significantly reduced collagen accumulation (7.9-fold), HSC activation indicated by reduced alpha smooth muscle actin+ and vimentin+ cells, and serum aminotransferase activity. Our studies demonstrate that activin A antagonist NUCC-555 promotes liver regeneration and halts fibrosis progression in CLD models, suggesting that blocking activin A signaling may represent a new approach to treating people with CLD.

Kinesin family member 12-related hepatopathy: A generally indolent disorder with elevated gamma-glutamyl-transferase activity.

Exome sequencing (ES) has identified biallelic kinesin family member 12 (KIF12) mutations as underlying neonatal cholestatic liver disease. We collected information on onset and progression of this entity. Among consecutively referred pediatric patients at our centers, diagnostic ES identified 4 patients with novel, biallelic KIF12 variants using the human GRCh38 reference sequence, as KIF12 remains incompletely annotated in the older reference sequence GRCh37. A review of these and of 21 reported patients with KIF12 variants found that presentation with elevated serum transaminase activity in the context of trivial respiratory infection, without clinical features of liver disease, was more common (n = 18) than manifest cholestatic disease progressing rapidly to liver transplantation (LT; n = 7). Onset of liver disease was at age <1 year in 15 patients; LT was more common in this group. Serum gamma-glutamyl transpeptidase activity (GGT) was elevated in all patients, and total bilirubin was elevated in 15 patients. Liver fibrosis or cirrhosis was present in 14 of 18 patients who were biopsied. The 16 different pathogenic variants and 11 different KIF12 genotypes found were not correlated with age of onset or progression to LT. Identification of biallelic pathogenic KIF12 variants distinguishes KIF12-related disease from other entities with elevated GGT.

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling.

This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications.

Modulation of the crosstalk between Keap1/Nrf2/HO-1 and NF-κB signaling pathways by Tomatidine protects against inflammation/oxidative stress-driven fulminant hepatic failure in mice

Fulminant hepatic failure (FHF) is the terminal phase of acute liver injury, which is characterized by massive hepatocyte necrosis and rapid hepatic dysfunction in patients without preexisting liver disease. There are currently no therapeutic options for such a life-threatening hepatic failure except liver transplantation; therefore, the terminal phase of the underlying acute liver injury should be avoided. Tomatidine (TOM), asteroidal alkaloid, may have different biological activities, including antioxidant and anti-inflammatory effects. Herein, the lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF mouse model was established to explore the protective potential of TOM and the underlying mechanisms of action. TOM pretreatment significantly inhibited hepatocyte necrosis and decreased serum aminotransferase activities in LPS/D-GalN-stimulated mice. TOM further increased the level of different antioxidant enzymes while reducing lipid peroxidation biomarkers in the liver. These beneficial effects of TOM were shown to be associated with targeting of NF-κB signaling pathways, where TOM repressed NF-κB activation and decreased LPS/D-GalN-induced TNF-α, IL-6, IL-1β, and iNOS production. Moreover, TOM prevented LPS/D-GalN-induced upregulation of Keap1 expression and downregulation of Nrf2 and HO-1 expression, leading to increased Nrf2-binding activity and HO-1 levels. Besides, TOM pretreatment repressed LPS/D-GalN-induced upregulation of proliferating cell nuclear antigen (PCNA) expression, which spared the hepatocytes from damage and subsequent repair following the LPS/D-GalN challenge. Collectively, our findings revealed that TOM has a protective effect on LPS/D-GalN-induced FHF in mice, showing powerful antioxidant and anti-inflammatory effects, primarily mediated via modulating Keap1/Nrf2/HO-1 and NF-κB/TNF-α/IL-6/IL-1β/iNOS signaling pathways.

Hypoglycemic and Hepatoprotective Activities of Coriander (Coriandrum sativum) Extract in Streptozocin Induced Diabetic Rats

The present study was designed to evaluate the role of Coriander (Coriandrum sativum) for management of diabetes instead of manufactured drugs, which led to many complications. Medicinal plants would be higher useful for this purpose because they are considered to be effective and non-toxic and safer than manufactured drugs. Aqueous extract of Coriander (C. sativum) was used to measurements their antidiabetic and hepatoprotective effects in streptozocin (STZ) induced diabetic male albino rats. Coriander (C. sativum) was given to the STZ induced diabetic rats at the concentration of 200 mg/kg body weight in different groups of three diabetic rats each orally once a day for 15 days. Body weight showed significant increase after 15 days of treatment with Coriander (C. sativum) extract compared with the normal control rats group (N). Blood glucose level on 15th day of treatment became significantly lower. The extract induced significant reduction in serum glucose, total lipids, total cholesterol, triglycerides level and transaminases (AST, ALT and γ-GT) activities. Liver glycogen content was significantly increased in treated animals compared to control group (N). The present data revealed insignificant changes in the serum total protein, albumin and globulin level during the experimental period. The lipid peroxidation determined was found to be decreased in plasma, liver and kidney of streptozocin induced diabetic rats treated with Coriander (C. sativum) extract (STZ/T) and rats group given Coriander (C. sativum) extract and then induced streptozocin (T/STZ), compared to control streptozocin induced diabetic rats group (STZ©). Glutathione reductase (GSH-R), glutathione peroxidase (GSH-P) and superoxide dismutase (SOD) activities were increased in liver and kidney of rat groups. These findings demonstrates that Coriander (C. sativum) extract have antioxidant effect for reducing lipid peroxidation in plasma and tissues and improve the liver function and antioxidant enzymes in treated rat groups compared to diabetic control rat group (STZ©). These observations revealed that the use of Coriander (C. sativum) extract can be recommended as natural antidiabetic, antioxidant and hypolipidemic activity agent. Findings of the present study suggest that the aqueous extract of Coriander (C. sativum) at the dose of 200 mg/kg body weight brings about significant beneficial effects in various biochemical parameters during diabetic and these effects are quite comparable with standard drug used to treat diabetes mellitus.

Hepatoprotective effect of the flavonoid fustin in a rat model of paracetamol-induced acute liver damage

Paracetamol (PCM)-induced toxicity is a well-established pharmacological model. Cotinus coggygria is a medicinal plant rich in polyphenols, including the flavonoid fustin. The aim of the present study was to evaluate the effects of the flavonoid fustin isolated from Cotinus coggygria heartwood in a model of PCM-induced liver damage. Male Wistar rats (n=48) were allocated to four groups: Control, PCM, F5+PCM, F10+PCM. The rodents were treated daily orally for nine consecutive days as follows: groups F5+PCM and F10+PCM – with fustin (suspended in a vehicle) at doses of 5 and 10 mg/kg, respectively; groups Control and PCM – with the vehicle. PCM was injected intraperitoneally (1.0 g/kg) on day 7. At the end of the experiment, serum and liver samples were prepared. PCM caused a severe liver damage confirmed by histopathological, immunohistochemical and biochemical indices. Compared to PCM group, in F5+PCM and F10+PCM groups, the hepatic necrosis, steatosis, ballooning degeneration, inflammation and expression of NF-κB were significantly reduced. Fustin treatment resulted in a significant reduction of serum activities of alanine aminotransferase and gamma-glutamyl transferase to levels that did not differ from the control values. The present study demonstrated a hepatoprotective effect of the flavonoid fustin in a rat model of acute paracetamol-induced toxicity.

Changes in rats serum aminotransferase activity during acute toxic hepatitis modeling

Changes in rats serum aminotransferase activity during acute toxic hepatitis modeling

Hepatoprotection of a Standardized Extract of Cultured Lentinula edodes Mycelia against Liver Injury Induced by Ischemia-Reperfusion and Partial Hepatectomy.

A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought to involve the induction of inflammatory mediators. However, whether ECLM affects inflammatory mediators caused by warm hepatic ischemia-reperfusion injury and partial hepatectomy (HIRI+PH) has not been clarified. In this study, we evaluated the protective effects of ECLM against liver damage caused by HIRI+PH. Rats were fed a normal diet (HIRI+PH) or a normal diet with 2% ECLM (HIRI+PH and ECLM) for ten days, then the liver and duodenal ligament were clamped and subjected to 15 min of hepatic ischemia. After 70% hepatectomy, the inflow occlusion was released, and liver and blood samples were collected at 3, 6, and 24 h. The effect of ECLM on mortality induced by 30 min of ischemia and hepatectomy was evaluated. The results showed that ECLM attenuated pathological liver damage, including apoptosis, in the rats treated with HIRI+PH, and decreased serum aminotransferase activity; ECLM decreased mRNA levels of the inflammation-related genes inducible nitric oxide synthase and C-X-C motif chemokine ligand 1, and increased mRNA levels of interleukin 10, an anti-inflammatory cytokine; ECLM increased hepatocyte growth factor mRNA levels and Ki-67 labeled nuclei in the liver at 24 h; ECLM significantly reduced HIRI+PH-induced mortality. In conclusion, ECLM may prevent HIRI+PH-induced liver injury in part by suppressing various inflammatory responses and promoting liver regeneration.

Activity of blood serum aminotransferases and their relationship with feeding and meat qualities of young pigs of different intensity of formation

Activity of blood serum aminotransferases and their relationship with feeding and meat qualities of young pigs of different intensity of formation

Short-term intake of fiber-rich oat bran but not spelt bran flake mix lowers bacterial endotoxin levels and improves health parameters in healthy, normal weight, young to middle-aged women

Diets low in dietary fiber have been associated with higher risks for non-communicable chronic diseases. We assessed in a single-blinded cross-over designed study if oat bran and spelt bran rich flake mixes, respectively, are suitable to increase general fiber intake in healthy women and impact intestinal microbiota composition, markers of intestinal barrier function, and general health parameters. Both interventions were associated with a significant increase in overall fiber intake but no marked changes of nutrient intake. Blood pressure was significantly lower after both interventions whereas cholesterol levels, alanine transaminase and aspartate transaminase activities in serum were only lower after the oat bran mix intervention. The latter was associated with a significant decrease of bacterial endotoxin in plasma but no change in intestinal microbiota composition. Our study suggests that fiber rich flake mixes are a suitable measure to increase dietary fiber intake, but health effects may differ between different dietary fibers.

Allyl methyl disulfide (AMDS) prevents N,N-dimethyl formamide-induced liver damage by suppressing oxidative stress and NLRP3 inflammasome activation

N,N-dimethylformamide (DMF), a widely consumed industrial solvent with persistent characteristics, can induce occupational liver damage and pose threats to the general population due to the enormous DMF-containing industrial efflux and emission from indoor facilities. This study was performed to explore the roles of allyl methyl disulfide (AMDS) in liver damage induced by DMF and the underlying mechanisms. AMDS was found to effectively suppress the elevation in the liver weight/body weight ratio and serum aminotransferase activities, and reduce the mortality of mice induced by DMF. In addition, AMDS abrogated DMF-elicited increases in malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels and decreases in glutathione (GSH) levels in mouse livers. The increase in macrophage number, mRNA expression of M1 macrophage biomarkers, and protein expression of key components in the NF-κB pathway and NLRP3 inflammasome induced by DMF exposure were all suppressed by AMDS in mouse livers. Furthermore, AMDS inhibited DMF-induced cell damage and NF-κB activation in cocultured AML12 hepatocytes and J774A.1 macrophages. However, AMDS per se did not significantly affect the protein level and activity of CYP2E1. Collectively, these results demonstrate that AMDS effectively ameliorates DMF-induced acute liver damage possibly by suppressing oxidative stress and inactivating the NF-κB pathway and NLRP3 inflammasome.

Protective effects of puerarin on liver tissue in Salmonella-infected chicks: a proteomic analysis

Salmonella enterica is a zoonotic bacterium that not only causes serious economic losses to the livestock and poultry industries but also seriously endangers human health. Long-term indiscriminate use of antibiotics has led to drug resistance in Salmonella, and thus the identification of alternatives to antibiotics is crucial. In this study, the effects of puerarin on the S. enterica-infected chickens were investigated. A total of 360 chicks were randomly assigned as the control group (CON), the S. enterica group (S), and puerarin-treatment group (P). Chicks in the P group were fed the basal diet supplemented with 50 (P50), 100 (P100), 200 (P200), and 400 (P400) mg/kg puerarin, respectively. It was found that puerarin treatment markedly altered the serum activities of aspartate aminotransferase (AST), alanine transaminase (ALT), and superoxide dismutase (SOD), together with the malondialdehyde (MDA) and total antioxidant capacity (T-AOC) contents in the serum. The mRNA expression of IL-6, IL-1β, TNF-α, Bcl-2, and caspase-8 in the livers of S. enterica-infected chicks was increased after infection but significantly reduced after treatment with puerarin. Histologic analysis showed that puerarin effectively mitigated morphological damage in the liver caused by S. enterica. Proteomic analysis revealed that S. enterica infection led to metabolic disorders in the liver, resulting in oxidative stress, increased inflammation, and significantly elevated levels of hepatocellular carcinoma biomarkers. The findings of the filtered sequencing were verified by using quantitative PCR (qPCR). Treatment with 100 mg/mL puerarin thus effectively alleviated disordered liver metabolism, reduced inflammation and oxidative damage and significantly reduced the levels of hepatocellular carcinoma biomarkers in the liver. The results suggest that puerarin has the potential to replace antibiotics to control Salmonella infection in poultry and thus improve food safety.

Fasudil inhibits the expression of C/EBP homologous protein to protect against liver injury in acetaminophen-overdosed mice

Acetaminophen (APAP) overdoses can cause severe liver injury. In this study, the protective effect of fasudil against APAP-induced liver injury was investigated. APAP (400 mg/kg) was administered to male C57BL/6J mice to induce liver injury, and fasudil (20 or 40 mg/kg) was injected 30 min before APAP administration. Fasudil markedly suppressed APAP-induced elevation in serum transaminase activity and hepatic necrosis and significantly reduced an increase in nitrotyrosine and DNA fragmentation. However, fasudil did not affect cytochrome P450 2E1 expression, N-acetyl-p-benzoquinone imine production or c-jun N-terminal kinase activation. In contrast, fasudil significantly inhibited an APAP-induced increase in expression of the transcription factor C/EBP homologous protein (CHOP) in the liver, accompanied by transcriptional suppression of ER stress-related molecules such as Ero1α, Atf4 and Grp78. These findings indicate that suppression of CHOP expression by fasudil exhibits a remarkable protective effect against APAP liver injury by regulating ER stress. We suggest that fasudil is a promising therapeutic candidate for treating APAP-induced liver injury.

Biomarkers of oral subacute toxicity of deltamethrin in exposed male Albino rats.

Deltamethrin is one of the most effective pyrethroid compounds, widely employed in veterinary medicine, public health, and farming. Deltamethrin-triggered oxidative stress largely causes serious harm to an organism. Acute toxicity of this compound was extensively investigated, while less information is available on its oral sub-acute effects. This study assessed, in the male Albino rats, the effects of oral gavage of either 0.874mg/kg (0.01 LD50) or 8.740mg/kg (0.10 LD50) of deltamethrin for successive 14days to investigate its effects on biomarkers and to detect the tissue injury in rats following subacute deltamethrin treatment. It was found that levels of glutathione peroxidase, superoxide dismutase, and catalase in the brain, kidney, and liver, alkaline phosphatase (ALP), and uric acid in serum, hematocrit, mean corpuscular volume (MCV), white blood cells (WBC)s, eosinophils, and basophils were significantly reduced compared with untreated rats. However, when rats were treated with deltamethrin for successive 14days, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities in serum and the levels of thiobarbituric acid reactive substances (TBARs) in brain, kidney, and liver, red blood cell distribution width (RDW-CV), total protein, monocytes, and basophils and the ratios of neutrophils to lymphocytes, an aggregated marker of systemic inflammation and systemic immune inflammation indexes, significantly increased compared with the control group. Histologic lesions were observed in the liver, kidney, brain, testis, and epidemies in rats exposed to subacute deltamethrin for 14days, and most tissues of rats treated with 0.10 LD50 of deltamethrin were more affected than those treated with 0.01 LD50. These findings strongly suggest that subacute exposure to deltamethrin caused significant systemic toxicity through oxidative stress resulting in biochemical and histological changes in the studied tissues. These findings highlight the potential harmful effects of deltamethrin and emphasize the importance of understanding the subacute effects of this compound, particularly in the context of veterinary medicine, public health, and farming.