Serum Aspartate Aminotransferase Activities Research Articles

Partial Replacement of Fishmeal with Poultry By-Product Meal in Diets for Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

The present study evaluated the effects of partially substituting fish meal (FM) with poultry by-product meal (PBPM) on the growth, muscle composition, and tissue biochemical parameters of coho salmon (Oncorhynchus kisutch) post-smolts. Five isonitrogenous (7.45% nitrogen) and isoenergetic (18.61 MJ/kg gross energy) experimental diets were made by substituting 0%, 10%, 20%, 40%, and 60% FM protein with PBPM protein, which were designated accordingly as PBPM0 (the control), PBPM10, PBPM20, PBPM40, and PBPM60, respectively. Each diet was fed to triplicates of ten post-smolts (initial individual body weight, 180.13 ± 1.32 g) in three floating cages three times daily (6:50, 11:50, and 16:50) to apparent satiation for 84 days. Both specific growth rate (SGR) and protein efficiency ratio did not differ significantly (p > 0.05) among the control, PBPM10, and PBPM20 groups, which were remarkably (p < 0.05) higher than those of the PBPM40 and PBPM60 groups. Feed conversion ratio varied inversely with SGR. The PBPM replacement had no remarkable effects on the morphological indices and proximal muscle components. The control and PBPM10 groups led to significantly higher muscle contents of leucine, lysine, and methionine than groups of higher PBPM inclusion. The groups of PBPM40 and PBPM60 obtained significantly (p < 0.05) higher serum alanine aminotransferase and aspartate aminotransferase activities than the control and low PBPM inclusion groups. The control group had significantly higher albumin and total cholesterol contents than the groups with PBPM inclusion. The control group had significantly higher triglycerides content than the PBPM60 group. The PBPM60 group had significantly lower contents of high-density lipoprotein, low-density lipoprotein, and total protein than the control and PBPM10 groups. The high PBPM replacement level up to 40% and 60% had adverse effects on hepatic malondialdehyde levels. The catalase and superoxide dismutase activities were not affected by low PBPM inclusion, but significantly decreased in high-PBPM-inclusion groups. Based on broken-line regression analysis of SGR and PER, the optimum dietary PBPM replacing level was evaluated to be 16.63-17.50% of FM protein for coho salmon post-smolts.

Protective Effect of Andropraphis Paniculata Aqueous Extract (EAAp) Against Isoniazid and Rifampicin-Induced Rat Liver Damage

Isoniazid (INH) and rifampicin (RIF) are first-line antituberculosis drugs (OAT) in tuberculosis treatment that are used for at least 6 months. The use of OAT has been associated with toxic reactions in the liver and causes hepatitis. This study aimed to determine the effect of an aqueous extract of Andrographis paniculata (EAAp) on liver damage induced by INH and RIF. Method: Male Sprague-Dawley rats weighing 250–300g were divided into 5 groups, each consisting of 6 mice. Animals were given isoniazid and rifampicin at 100 mg/kg, respectively, to induce liver damage, silymarin (25 mg/kg) for the positive control group, and Ap extract at doses of 200mg and 300 mg/kg for the test group. All treatments were given orally once daily for 28 days. Measurement of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, and liver histopathology levels was carried out to determine the effect of EAAp on liver damage by INH and RIF. Results: Rats treated with INH+RIF were hepatotoxic, as evidenced by increased serum ALT, AST, and ALP activity, total bilirubin levels, and histopathological changes in the liver. Administration of Ap extract doses of 200 mg/kg and 300 mg/kg significantly decreased liver biochemical and histological changes caused by OAT. Conclusions: EAAp has a protective effect against hepatotoxic-induced INH and RIF in animal models.

Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways.

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1β, transforming growth factor-β1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.

Effects of Ocimum basilicum essential oil and ginger extract on serum biochemistry, oxidative stress and gill tissue damage of pearl gentian grouper during simulated live transport.

This study explored the effects of the essential oil of Ocimum basilicum (EOOB) and ginger extract (GE) during the transportation of pearl gentian grouper from water quality, serum biochemistry, oxidative stress, meat flavor, and gill tissue morphology. Fish (450 ± 50g) were allocated to the following 5 treatments: control group (fish transported in water only), 5mg/LEOOB, 10mg/LEOOB, 3mg/LGE, and 6mg/LGE and transported in insulation boxes (66 × 51 × 37.8cm) for 72h. Samples were taken at 0, 12, 36, 60, and 72h immediately after transport. It was found that 10mg/LEOOB and 6mg/LGE could reduce the levels of total ammonia nitrogen (TAN), dissolved oxygen (DO), water pH, serum glucose (GLU), cortisol (COR), liver superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPX), increase the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), as well as significantly increase the total free amino acid (TFAA) content in muscle compared to the control group (P < 0.05). In addition, by observing the microstructure of gill tissue, it was found that compared with untreated grouper, the morphological damage of gill tissue in EOOB and GE treatment was alleviated. These results indicated that adding appropriate amounts of EOOB and GE to transport water could improve the water quality, relieve stress, and lower energy metabolism of grouper during transport. The results of this research will help to improve the survival rate of grouper after transportation and decrease economic losses to fishery.

Icariin Supplementation Suppresses the Markers of Ferroptosis and Attenuates the Progression of Nonalcoholic Steatohepatitis in Mice Fed a Methionine Choline-Deficient Diet.

Icariin, a flavonoid abundant in the herb Epimedium, exhibits anti-ferroptotic activity. However, its impact on nonalcoholic steatohepatitis (NASH) development remains unclear. This study aimed to investigate the potential role of icariin in mitigating methionine choline-deficient (MCD) diet-induced NASH in C57BL/6J mice. The results showed that icariin treatment significantly reduced serum alanine aminotrasferase and aspartate aminotransferase activities while improving steatosis, inflammation, ballooning, and fibrosis in the liver tissues of mice fed the MCD diet. These improvements were accompanied by a substantial reduction in the hepatic iron contents and levels of malondialdehyde and 4-hydroxynonenal, as well as an increase in the activities of catalase and superoxide dismutase. Notably, icariin treatment suppressed the hepatic protein levels of ferroptosis markers such as acyl-CoA synthetase long-chain family member 4 and arachidonate 12-lipoxygenase, which were induced by the MCD diet. Furthermore, transmission electron microscopy confirmed the restoration of morphological changes in the mitochondria, a hallmark characteristic of ferroptosis, by icariin. Additionally, icariin treatment significantly increased the protein levels of Nrf2, a cystine/glutamate transporter (xCT), and glutathione peroxidase 4 (GPX4). In conclusion, our study suggests that icariin has the potential to attenuate NASH, possibly by suppressing ferroptosis via the Nrf2-xCT/GPX4 pathway.

Toxicological and histopathological alterations in the heart of young and adult albino rats exposed to mosquito coil smoke

Mosquito coil repellents are well-known indoor air pollutant with significant health concerns. The present study investigated the toxic effects of mosquito coil smoke on the heart of young and adult male rats. The animals were subjected to the smoke for 6 h/day, 6 days/week, for 4 weeks. Within the first hour after lighting the coil, significant amounts of formaldehyde, total volatile organic compounds, and particulate matter (PM2.5 and PM10) were detected. Both exposed ages, particularly the young group, showed a significant increase in the activities of serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, and the levels of troponin I, myoglobin, Na+ levels, lipid profile, and inflammatory markers (interleukin-6 and C-reactive protein) as well as a significant decrease in K+ levels and cardiac Na–K ATPase activity, indicating development of cardiac inflammation and dysfunction. Furthermore, the toxic stress response was validated by significant downregulation at expression of the detoxifying enzyme cytochrome p450. Histopathological studies in both age groups, especially the young group, revealed cardiomyocyte degeneration and necrotic areas. Moreover, upregulation at the pro-apoptotic markers, caspase3, P53, and cytochrome C expressions, was detected by immunohistochemical approach in heart sections of the exposed groups. Finally, the myocardial dysfunctional effects of the coil active ingredient, meperfluthrin, were confirmed by the docking results which indicated a high binding affinity of meperfluthrin, with Na–K ATPase and caspase 3. In conclusion, both the young and adult exposed groups experienced significant cardiac toxicity changes evidenced by cell apoptosis and histopathological alterations as well as disruption of biochemical indicators.Graphical

Castanopsis sieboldii Extract Alleviates Acute Liver Injury by Antagonizing Inflammasome-Mediated Pyroptosis.

Castanopsis sieboldii (CS), a subtropical species, was reported to have antioxidant and antibacterial effects. However, the anti-inflammatory effects of CS have not been studied. This study aimed to investigate whether the 70% ethanol extract of the CS leaf (CSL3) inhibited lipopolysaccharide (LPS)-induced inflammatory responses and LPS and ATP-induced pyroptosis in macrophages. CSL3 treatment inhibited NO release and iNOS expression in LPS-stimulated cells. CSL3 antagonized NF-κB and AP-1 activation, which was due to MAPK (p38, ERK, and JNK) inhibition. CSL3 successfully decreased NLRP3 inflammasome activation and increased IL-1β expression. CSL3 treatment diminished LPS and ATP-induced pore formation in GSDMD. The in vivo effect of CSL3 on acute liver injury was evaluated in a CCl4-treated mouse model. CCl4 treatment increased the activity of serum alanine aminotransferase and aspartate aminotransferase, which decreased by CSL3. In addition, CCl4-induced an increase in TNF-α, and IL-6 levels decreased by CSL3 treatment. Furthermore, we verified that the CCl4-induced inflammasome and pyroptosis-related gene expression in liver tissue and release of IL-1β into serum were suppressed by CSL3 treatment. Our results suggest that CSL3 protects against acute liver injury by inhibiting inflammasome formation and pyroptosis.

Efficacy of dietary thiamine supplementation on growth performance, digestive enzymes, immunological responses, and antioxidant capacity of juvenile beluga (Huso huso)

The aim of the current study was to investigate the beneficial effects of dietary thiamine supplementation on physiological, immunological and antioxidant responses in juvenile beluga, Huso huso. The juvenile fish (∼ 3 g) were fed four times a day with diets containing 0 (control), 5 (5 T), 10 (10 T), and 20 (20 T) mg kg−1 thiamine for 12 weeks. Significant increases were observed in growth performance indicators of the fish fed different levels of thiamine, compared to the control group and the best performance was observed in 10 T treatment. The carcass protein content significantly increased in the thiamine-treated fish and the highest protein content was observed in the 10 T treatment. Digestive enzymes’ activities (pepsin, trypsin, lipase, and amylase) significantly increased in the fish fed the thiamine-supplemented diets. The serum alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase activities significantly decreased in the 10 T and 20 T treatments, compared to the control group. Dietary thiamine supplementation significantly increased the serum lysozyme, alternative complement activities, and IgM level, compared to the control diet and the highest lysozyme activity and IgM level were observed in the 10 T and 20 T treatments. The hepatic superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase, transketolase activities of 10 T and 20 T treatments were significantly higher than those of the control treatment. The hepatic catalase activities in the thiamine-treated fish were significantly higher than that of the control fish. Contrastingly, the hepatic malondialdehyde contents of the 5 T, 10 T, and 20 T treatments were significantly lower than the control treatment. Although all the dietary thiamine levels (5–20 mg kg−1) showed beneficial effects on different tested parameters, 10 mg kg−1 was the most beneficial level and is recommended for dietary inclusion to improve the growth and health of juvenile beluga.

Biochemical Assessment of Solid-State Fermented Elephant Grass and its Potential Incorporation in Broiler's Diets

The objective of this study was to determine if incorporating pre-treated ensiled elephant grass into broiler feed could help meet the rising demand for animal protein. The elephant grass underwent solid-state fermentation for seven days and ensiling in airtight nylon bags for 21 days. Compared to the control, pre-treated ensiled elephant grass exhibited a significant increase in soluble protein concentration (p&lt;0.05) during fermentation. However, the glucose concentration was significantly lower (p&gt;0.05) in the pre-treated ensiled elephant grass after fermentation than in the control. Elephant grass that was solid-state fermented and ensiled with Rhizopus oligosporus demonstrated the highest percentage inhibition (22.4±0.5%). The pre-treated ensiled elephant grass had significantly higher mannanase activity (p&lt;0.05) than the control. In terms of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities, there were no significant differences between the control group and the experimental group fed with diets composed of ensiled elephant grass, ensiled elephant grass fermented with R. oligosporus, or solid-state fermented and ensiled elephant grass with R. oligosporus and urea in a 25% maize replacement. In conclusion, ensiled elephant grass can replace 25% maize in broiler starter feed, and the animal feed industry could benefit from the mannanase identified in this study.

Cryptotanshinone ameliorates hemorrhagic shock-induced liver injury via activating the Nrf2 signaling pathway.

Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activitywere suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.

Deleterious Effects of Polypropylene Microplastic Ingestion in Nile Tilapia (Oreochromis niloticus).

The effect of daily ingestion of polypropylene microplastic on the health of tilapia, Oreochromis niloticus, was evaluated. 60 fish (± 200g) were placed in 6 aquariums (n = 10, 100L each), constituting the following treatments: Control (without the addition of polymer), fed with 100 and 500µg of polypropylene/kg of body weight (b.w.), respectively. After 30 days of feeding, the animals were submitted to blood collection for hemogram and biochemical study and later euthanized for gut microbiological analysis, somatic index of liver, spleen, heart, kidney, stomach, and intestine. In the serum biochemical study, an increase in cholesterol and serum Aspartate Aminotransferase (AST) activity levels was observed in animals treated with 500µg of polypropylene. Tilapia-fed polypropylene in the diet showed an increase in thrombocyte and total leukocyte counts, marked by a significant increase in the number of circulating lymphocytes. The results of the somatic study revealed a significant increase in the stomach, liver, and heart of tilapia fed with the polymer. Increase in the number of Gram-negative microorganisms and decrease in mesophilic aerobic microorganisms were observed in the gut of fish exposed to the polymer, including a dose-response effect was observed for these analyses. Therefore, tilapias fed daily with diets containing polypropylene for 30 consecutive days showed deleterious effects, resulting in systemic inflammatory disturbs by altering liver functions, leukocyte profile, and organ morphometry, as well as changes in the intestinal microbiota. Such results demonstrate the impairment of fish health, highlighting the need for further studies that evaluate the impact of microplastics on aquatic organisms.

Hepatoprotective effects of chlorogenic acid on mice exposed to aflatoxin B1: Modulation of oxidative stress and inflammation

Aflatoxin B1 (AFB1) is widely distributed in crops and feeds, and ingestion of AFB1-contaminated crops is harmful to human/animal health. This study was designed to investigate hepatoprotective effects of chlorogenic acid (CGA), due to its excellent antioxidant and anti-inflammatory activities, on mice exposed to AFB1. Male Kunming mice were orally fed with CGA prior to daily AFB1 exposure for 18 consecutive days. The results showed that CGA treatment reduced the serum activity of aspartate aminotransferase, hepatic malondialdehyde content and pro-inflammatory cytokines synthesis, prevented histopathological changes of the liver, increased hepatic glutathione level, catalase activity and IL10 mRNA expression in mice subjected to AFB1. Taken together, CGA exerted the protective effect on AFB1-induced hepatic damage by modulating redox status and inflammation, suggesting that CGA may be a candidate compound for the treatment of aflatoxicosis.

A retrospect study based on real-world data to observe metabolic function in cancer patients using albumin-bound paclitaxel

There is substantial evidence that albumin-bound paclitaxel (nab-paclitaxel) is effective and safe for the treatment of breast, lung and pancreatic cancers. However, it can still cause adverse effects by affecting cardiac enzymes, hepatic enzyme metabolism and blood routine related indicators, which affects the use of chemotherapy for a full course of treatment. However, there are no relevant clinical studies to systematically observe the effects and dynamics of albumin-bound paclitaxel on cardiac enzymes, liver enzyme metabolism, and routine blood-related indices. The purpose of our study was to determine the levels of serum creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), white blood cells (WBC) and hemoglobin (HGB) in cancer patients treated with albumin-conjugated paclitaxel. This study retrospectively analyzed 113 patients with cancer. Patients who had received two cycles of nab-paclitaxel 260 mg/m2 (administered intravenously on days 1, 8, and 15 of each 28-day cycle) were selected. Serum Cre, AST, ALT, LDH, CK, and CK-MB activities, WBC counts, and HGB levels were measured before and after treatment with two cycles. Fourteen cancer types were analyzed. The distribution of cancer types in patients was mainly concentrated in lung, ovarian, and breast cancer. Nab-paclitaxel treatment markedly decreased Cre, AST, LDH, and CK activities in the serum and WBC counts and HGB levels, respectively. Serum Cre and CK activities and HGB levels were remarkably downregulated at baseline compared to healthy controls. Patients receiving nab-paclitaxel treatment cause metabolic disorders in tumor patients by reducing the decrease of Cre, AST, LDH, CK, CK-MB, WBC and HGB indexes, thus inducing the occurrence of cardiovascular events, hepatotoxic events and fatigue and other symptoms. Therefore, for tumor patients, although receiving nab-paclitaxel improves the anti-tumor effect, it is still necessary to closely monitor the changes of related enzymatic and routine blood indicators, so as to detect and intervene at an early stage.

Lipid nanoparticle delivery of siRNA targeting Cyp2e1 gene attenuates subacute alcoholic liver injury in mice.

To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice. siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR. Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01). The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.

α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice.

Sepsis is one of the most fatal inflammatory diseases with multiple organ failure caused by pathological infection. α-Hederin, a monodesmosidic triterpenoid saponin, has many biological activities including anti-inflammation. This study aimed to investigate the effect of α-Hederin on lung and liver injuries in septic mice. Mice underwent cecal ligation and puncture-induced sepsis were intraperitoneally injected with 0.3 or 3 mg/kg α-Hederin. α-Hederin treatment dose-dependently attenuated the lung and liver injuries in septic mice. Correspondingly, α-Hederin significantly decreased malondialdehyde production, increased the levels of superoxide dismutase and glutathione in lung tissues, reduced serum alanine aminotransferase and aspartate aminotransferase activities, and suppressed the levels of TNF-α and IL-6 in both tissues and in the serum. Moreover, α-Hederin augmented CD206 level and inhibited the productions of CD86 and iNOS in lung and liver tissues of septic mice. Importantly, p-p65/p65 was suppressed, whereas IκB was elevated by α-Hederin. In conclusion, α-Hederin could improve the lung and liver injuries in mice with sepsis by regulating macrophage M1/M2 polarization and inhibiting the activation of NF-κB signaling pathway.

Hepatoprotective Effects of Biochanin A Against Acetaminophen-induced Liver Toxicity in Mice

Background: Acetaminophen (APAP), a common analgesic agent, is hepatotoxic in overdose. N-acetylcysteine (NAC), as an APAP antidote, shows anaphylactic reactions and has low efficacy in APAP poisoning in high doses. Objectives: This study was designed to examine the hepatoprotective effect of biochanin A (BA) in a mice model of acetaminophen-induced hepatotoxicity. Methods: To evaluate APAP-induced oxidative stress, the liver tissue level of malondialdehyde (MDA) and glutathione (GSH) and the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), catalase, and superoxide dismutase (SOD) were measured. Histological analysis was performed. Results: APAP-induced hepatotoxicity was manifested by inflammation, acinar hepatic necrosis, and fatty degeneration, as well as an increase in the levels of ALP, ALT, AST, MDA, and a decrease in the SOD, catalase (CAT), and GSH. Pre-treatment with BA at low doses (10 and 20 mg/kg) reduced ALT, AST, and MDA levels and raised the SOD, GSH, and CAT levels. Moreover, it normalized the structure of liver tissue. Conclusions: The results of this study indicated that BA protected the liver from APAP-induced injury. Protection may be due to the inhibition of oxidative stress, which reduces liver inflammation.

Schizandrin C regulates lipid metabolism and inflammation in liver fibrosis by NF-κB and p38/ERK MAPK signaling pathways.

Liver fibrosis is considered a sustained wound healing response and metabolic syndrome, and its therapy is of great significance for chronic liver disease. Schizandrin C, as one lignan from hepatic protectant Schisandra chinensis, can depress the oxidative effect and lipid peroxidation, and protect against liver injury. In this study, C57BL/6J mice were used to estimate a liver fibrosis model by CCl4, and Schizandrin C exerted an anti-hepatic fibrosis effect, as evidenced by decreased alanine aminotransferase, aspartate aminotransferase and total bilirubin activities in serum, lower hydroxyproline content, recuperative structure and less collagen accumulation in the liver. In addition, Schizandrin C reduced the expressions of alpha-smooth muscle actin and type Ι collagen in the liver. In vitro experiments also revealed that Schizandrin C attenuated hepatic stellate cell activation in both LX-2 and HSC-T6 cells. Furthermore, lipidomics and quantitative real-time PCR analysis revealed that Schizandrin C regulated the lipid profile and related metabolic enzymes in the liver. In addition, the mRNA levels of inflammation factors were downregulated by Schizandrin C treatment, accompanied by lower protein levels of IκB-Kinase-β, nuclear factor kappa-B p65, and phospho-nuclear factor kappa-B p65. Finally, Schizandrin C inhibited the phosphorylation of p38 MAP kinase and extracellular signal-regulated protein kinase, which were activated in the CCl4 fibrotic liver. Taken together, Schizandrin C can regulate lipid metabolism and inflammation to ameliorate liver fibrosis by nuclear factor kappa-B and p38/ERK MAPK signaling pathways. These findings supported Schizandrin C as a potential drug for liver fibrosis.

A Study of Heavy Metal Status and its Relationship with Hematologic and Biochemical Indices in River Buffaloes in Southwest Iran.

Heavy metals are among the most important environmental pollutants which accumulate in various organs and are associated with several toxic effects. This study was performed to determine the status of heavy metals in river buffaloes in Khuzestan province, Iran, and its relationship with hematologic and serum biochemical parameters. A total of 103 apparently healthy buffaloes were sampled from the region. The concentration of heavy metals, including lead (Pb), mercury (Hg), and cadmium (Cd), was determined in serum samples by atomic spectroscopy. In addition, complete blood counts and serum biochemical profiles were assessed. The serum concentration of Cd, Pb, and Hg in the sampled buffaloes, as mean±standard error, were 0.55±0.01, 6.51±0.10, and 6.28±0.09 µg/l, respectively, which are within the permissible serum levels in the livestock. Serum Cd and Hg levels showed no significant relationship with hematologic or biochemical analytes. However, there were significant negative correlations between Pb levels and phosphorus, magnesium, sodium, as well as potassium concentrations, while serum iron was positively correlated with lead (P<0.05). In addition, there was a significant positive correlation between Hg level and serum aspartate aminotransferase activity (P<0.05). Despite the fact that river buffaloes in Khuzestan spend a long time daily in the Karun River with high industrial pollution, no serum evidence of heavy metal toxicity was found in these animals. It can be suggested that river buffaloes in Khuzestan seem to be resistant to the environmental pollution caused by heavy metals. However, further studies are required to confirm this issue and identify its possible explanations.

Intestinal microbiomics and hepatic metabolomics insights into the potential mechanisms of probiotic Bifidobacterium pseudolongum CCFM1253 preventing acute liver injury in mice.

Bifidobacterium pseudolongum is widely exists in mammal gut and its abundance is associated with human and animal health. The present study aimed to investigate the potential mechanisms of B. pseudolongum CCFM1253 on protecting against lipopolysaccharide (LPS)-induced acute liver injury (ALI) by metagenomic analysis and liver metabolomic profiles. Bifidobacterium pseudolongum CCFM1253 preintervention remarkably attenuated the influence of LPS on serum alanine transaminase and aspartate amino transferase activities. B. pseudolongum CCFM1253 preintervention remarkably attenuated the inflammation responses (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and elevated antioxidative enzymes activities [total antioxidant capacity, superoxide dismutase, catalase, and glutathione peroxidase] in ALI mice by intervening in the Nf-kβ and Nrf2 pathways, respectively. Bifidobacterium pseudolongum CCFM1253 treatment elevated the proportion of Alistipes and Bifidobacterium, and decreased the proportion of uncultured Bacteroidales bacterium, Muribaculum, Parasutterella and Ruminococcaceae UCG-010 in ALI mice, which were strongly correlated with the inhibition of inflammation responses and oxidative stress. Untargeted liver metabolomics exhibited that the hepatoprotective efficacy of B. pseudolongum CCFM1253 might be achieved by altering liver metabolites-related riboflavin metabolism, phenylalanine metabolism, alanine, citrate cycle (tricarboxylic acid cycle), and so on. Furthermore, riboflavin exposure could control the contents of malondialdehyde, superoxide dismutase, and catalase in hydrogen peroxide-treated HepG2 cells. Bifidobacterium pseudolongum CCFM1253 can effectively alleviate inflammatory response and oxidative stress, and regulate the intestinal microbiota composition and liver metabolism, and elevate the liver riboflavin content in LPS-treated mice. Therefore, B. pseudolongum CCFM1253 could serves as a potential probiotic to ameliorate the host health. © 2023 Society of Chemical Industry.

Kefir peptides attenuate atherosclerotic vascular calcification and osteoporosis in atherogenic diet-fed ApoE -/- knockout mice.

Aims: Vascular calcification (VC) and osteoporosis were previously considered two distinct diseases. However, current understanding indicates that they share common pathogenetic mechanisms. The available medicines for treating VC and osteoporosis are limited. We previously demonstrated that kefir peptides (KPs) alleviated atherosclerosis in high-fat diet (HFD)-induced apolipoprotein E knockout (ApoE -/- ) mice. The present study further addressed the preventive effects of KPs on VC and osteoporosis in ApoE -/- mice fed a high-cholesterol atherogenic diet (AD). Main methods: Seven-week-old ApoE -/- and wild-type C57BL/6 mice were randomly divided into five groups (n = 6). The development of VC and osteoporosis was evaluated after AD feeding for 13weeks in KP-treated ApoE -/- mice and compared to C57BL/6 and ApoE -/- mice fed a standard chow diet (CD). Key findings: The results indicated that KP-treated ApoE -/- mice exhibited lower serum total cholesterol, oxidized low-density lipoprotein (ox-LDL), malondialdehyde (MDA) levels, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine kinase (CK) activities, which suggested that KPs prevented hyperlipidemia and possible damages to the liver and muscle in ApoE -/- mice. KPs reduced serum tumor necrosis factor-α (TNF-α) and the local expression of TNF-α, IL-1β, and macrophage-specific CD68 markers in aortic tissues, which suggested that KPs inhibited inflammatory responses in AD-fed ApoE -/- mice. KPs reduced the deposition of lipid, collagen, and calcium minerals in the aortic roots of AD-fed ApoE -/- mice, which suggested that KPs inhibited the calcific progression of atherosclerotic plaques. KPs exerted osteoprotective effects in AD-fed ApoE -/- mice, which was evidenced by lower levels of the bone resorption marker CTX-1 and higher levels of the bone formation marker P1NP. KPs improved cortical bone mineral density and bone volume and reduced trabecular bone loss in femurs. Significance: The present data suggested that KPs attenuated VC and osteoporosis by reducing oxidative stress and inflammatory responses in AD-fed ApoE -/- mice. Our findings contribute to the application of KPs as preventive medicines for the treatment of hyperlipidemia-induced vascular and bone degeneration.