Evaluation of the protective effect of coenzyme Q10 on hepatotoxicity caused by acute phosphine poisoning.

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100 mg/kg), AlP at 12 mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100 mg/kg doses via Intraparietal (ip) injections. After 24 h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.

Effectiveness of the ALT/AST ratio for predicting insulin resistance in a Korean population: A large-scale, cross-sectional cohort study.

Insulin resistance is a common pathophysiology in patients with type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Thus, screening for the risk of insulin resistance is important to prevent disease progression. We evaluated the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio to predict insulin resistance in the general population, regardless of comorbidities. Datasets from the 2015, 2019, and 2020 Korea National Health and Nutrition Examination Surveys were used, and the following four indices were implemented to indicate insulin resistance: fasting serum glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and ß-cell function. We analyzed the degree of association between the liver enzyme profile and insulin resistance indices using Pearson's correlation coefficient and determined the associations using linear or logistic regression analysis. Accordingly, ALT levels in both sexes were positively and consistently correlated with the four aforementioned insulin resistance indices in stratification analyses based on diabetes, dyslipidemia, alcohol consumption, and obesity status. In multivariate linear regression, when comparing with ALT levels, the ALT/AST ratio exhibited superior predictive performance for fasting serum glucose and HOMA-ß in Korean men and improved outcomes for all insulin resistance indices in Korean women. In this analysis that included a large community-based population, the ALT/AST ratio was a more useful predictive marker than the HOMA-IR. Regarding the predicted presence or absence of insulin resistance, the ALT/AST ratio could better predict HOMA-IR than the ALT level alone in Koreans. A simple, precise marker that represents the ALT/AST ratio could be a practical method to screen for insulin resistance in the general population, regardless of diabetes mellitus, alcohol intake, and sex.

The Glucose-Succinate Pathway: A Crucial Anaerobic Metabolic Pathway in the Scallop Chlamys farreri Experiencing Heat Stress.

Recently, the increase in marine temperatures has become an important global marine environmental issue. The ability of energy supply in marine animals plays a crucial role in avoiding the stress of elevated temperatures. The investigation into anaerobic metabolism, an essential mechanism for regulating energy provision under heat stress, is limited in mollusks. In this study, key enzymes of four anaerobic metabolic pathways were identified in the genome of scallop Chlamys farreri, respectively including five opine dehydrogenases (CfOpDHs), two aspartate aminotransferases (CfASTs) divided into cytoplasmic (CfAST1) and mitochondrial subtype (CfAST2), and two phosphoenolpyruvate carboxykinases (CfPEPCKs) divided into a primitive type (CfPEPCK2) and a cytoplasmic subtype (CfPEPCK1). It was surprising that lactate dehydrogenase (LDH), a key enzyme in the anaerobic metabolism of the glucose-lactate pathway in vertebrates, was absent in the genome of scallops. Phylogenetic analysis verified that CfOpDHs clustered according to the phylogenetic relationships of the organisms rather than substrate specificity. Furthermore, CfOpDHs, CfASTs, and CfPEPCKs displayed distinct expression patterns throughout the developmental process and showed a prominent expression in muscle, foot, kidney, male gonad, and ganglia tissues. Notably, CfASTs displayed the highest level of expression among these genes during the developmental process and in adult tissues. Under heat stress, the expression of CfASTs exhibited a general downregulation trend in the six tissues examined. The expression of CfOpDHs also displayed a downregulation trend in most tissues, except CfOpDH1/3 in striated muscle showing significant up-regulation at some time points. Remarkably, CfPEPCK1 was significantly upregulated in all six tested tissues at almost all time points. Therefore, we speculated that the glucose-succinate pathway, catalyzed by CfPEPCK1, serves as the primary anaerobic metabolic pathway in mollusks experiencing heat stress, with CfOpDH3 catalyzing the glucose-opine pathway in striated muscle as supplementary. Additionally, the high and stable expression level of CfASTs is crucial for the maintenance of the essential functions of aspartate aminotransferase (AST). This study provides a comprehensive and systematic analysis of the key enzymes involved in anaerobic metabolism pathways, which holds significant importance in understanding the mechanism of energy supply in mollusks.

Leucine zipper as a bridge for transaminase self-assembly: A fusion enzyme for efficient chiral conversion of d-phenylglycine.

Amino acid transferase is a family of enzymes used to catalyze and separate chiral amino acids. However, due to the low efficiency, by-products and reverse reactions occur in cascade reactions. Therefore, in the research, phenylglycine aminotransferase and aspartate aminotransferase were self-assembled in vitro by leucine zipper. The self-assembled enzyme system with d-phenylglycine and α-ketoglutarate as substrates were used for the chiral transformation reaction. By studying the enzyme combination, kinetic reaction stability and catalytic efficiency, it was found that the self-assembled enzyme showed improved stability and better affinity to the substrate than the control and achieved only ee value of 17.86% for the control at the substrate ratio was 1:2. In contrast, the self-assembled enzyme basically catalyzed the complete conversion of d-Phg to l-Phg, with the ee value as 99%. These results demonstrated the feasibility of the leucine zipper and the conversion of d-phenylglycine to the l-type by fusion enzyme.

Time-of-day dependence of running averages for some components of metabolic panels at our hospital: Relation to strategy for patient-based quality control.

BACKGROUND AND OBJECTIVES: We assessed properties of running averages for our hospital's most common chemistry analytes, for use in real-time patient-based quality control (PBQC). We determined whether there was dependence of any running averages on 24-h clock time (time-of-day, TOD). MATERIALS AND METHODS: We analyzed 3-months' data for measurements of 13 metabolic panel components. Running averages for 20 consecutive results (20-mers) were computed for data restricted to results within reference intervals. This produced an overall mean (X) and standard-deviation (SD) of 20-mers for each analyte. We then computed the average 20-mer result (Y) reported within 1-h bins across 24-hour clock time (t). Y(t) was regarded as having TOD-dependence if either nadir or apex values for |Y-X| exceeded 0.5 SD, occurring within a contiguous series of at least 4 Y(t) values on one side of the mean. RESULTS: Seven analytes (albumin, aspartate aminotransferase, calcium, chloride, CO2, potassium, total protein) demonstrated TOD-dependence of running means for 20-mers. CONCLUSIONS: At our hospital, TOD-dependence of running means was identified for 7 of 13 metabolic panel analytes. TOD-dependence is likely to be hospital-specific. Utilization of TOD-dependent targets for PBQC, rather than fixed targets, would be appropriate in these cases.

Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

BrdU does not induce hepatocellular damage in experimental Wistar rats.

Bromodeoxyuridine (BrdU) is used in studies related to cell proliferation and neurogenesis. The multiple intraperitoneal injections of this molecule could favor liver function profile changes. In this study, we evaluate the systemic and hepatocellular impact of BrdU in male adult Wistar rats in 30 %-partial hepatectomy (PHx) model. The rats received BrdU 50 mg/Kg by intraperitoneal injection at 0.5, 1, 2, 3, 6, 9 and 16 days after 30 %-PH. The rats were distributed into four groups as follows, control, sham, PHx/BrdU(-) and PHx/BrdU(+). On day 16, we evaluated hepatocellular nuclei and analyzed histopathological features by haematoxylin-eosin stain and apoptotic profile was qualified by caspase-3 presence. The systemic effect was evaluated by liver markers such as alanine transferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, total proteins and serum albumin content. The statistical analysis consisted of a student t-test and one-way ANOVA. BrdU did not induce apoptosis or hepatocellular damage in male rats. Multiple administrations of BrdU in male rats did not induce significant decrease body weight, but increased serum ALT and LDH levels were found. Our results show that the BrdU does not produce hepatocellular damage.

Crystal structure of an aspartate aminotransferase Lpg0070 from Legionella pneumophila.

Legionella pneumophila aspartate aminotransferase (Lpg0070) is a member of the transaminase and belongs to the pyridoxal 5'-phosphate (PLP)-dependent superfamily. It is responsible for the transfer of α-amino between aspartate and α-ketoglutarate to form glutamate and oxaloacetate. Here, we report the crystal structure of Lpg0070 at the resolution of 2.14 Å and 1.7 Å, in apo-form and PLP-bound, respectively. Our structural analysis revealed the specific residues involved in the PLP binding and free form against PLP-bound supported conformational changes before substrate recognition. In vitro enzyme activity proves that the absence of the N-terminal arm reduces the enzyme activity of Lpg0070. These data provide further evidence to support the N-terminal arm plays a crucial role in catalytic activity.

Effect of glyphosate-based herbicide roundup on hemato-biochemistry of Labeo rohita (Hamilton, 1822) and susceptibility to Aeromonas hydrophila infection.

In the present study, comprehensive research was executed to investigate the salient toxic effects of glyphosate herbicide in static water system by evaluating the haemato-biochemical profiles of Labio rohita. A challenge study against Aeromonas hydrophila was conducted to determine disease susceptibility of the fish, treated to varying concentrations of commercial-grade glyphosate herbicide. A static range finding bioassay and definitive test revealed that the 96-h LC50 value of glyphosate was 10.16 mg L-1. The experimental fish were subjected to three sub-lethal concentrations of 2.06, 1.03, and 0.63 mg l-1 for 28 days and changes were documented bi-fortnightly to study haemato-biochemical alterationsin the fish. Significantly (p < 0.05) low values in red blood corpuscles (RBC), hemoglobin (Hb), and hematocrit value (Hct) were documented. In contrast, a significant (p < 0.05) escalation in white blood corpuscles (WBC) was documented in comparison to the control. Biochemical and stress markers such as blood glucose, total protein, and alkaline phosphatase (ALP) were significantly (p < 0.05) low, whereas serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) escalated significantly (p < 0.05). Chronic exposure to glyphosate, on the other hand, had the least effect on the Na+ and K+ ions. Further, a challenge assay against A. hydrophila at three sub-lethal glyphosate concentrations demonstrated a synergistic impact that reduced the fish survivability. The findings conclude that persistent low glyphosate concentrations in aquatic ecosystems show significant pathophysiological changes in L. rohita, with increased vulnerability to infections. Altogether, our findings indicate the need to further study the possible assessment for a sustainable bio-remediation technique, mitigation of the detrimental effects of glyphosate exposure in fish, and recommendation of an acceptable residue concentration of the glyphosate in aquatic ecosystem.

Portable dual-channel blood enzyme analyzer for point-of-care liver function detection.

Because the liver is an important metabolic center in the human body, the reliability and timeliness of chronic liver disease diagnosis are particularly important. Alanine aminotransferase and aspartate transaminase are the two most important liver function indicators, and their test results are crucial in the diagnosis of liver diseases. However, the simultaneous detection of these two indicators is currently restricted by the need for expensive equipment and complicated detection processes. This study proposes a portable dual-channel blood enzyme analyzer (BEA) for point-of-care-testing. The device uses photometric reflectance to quantify the enzyme concentration by evaluating the reflected light intensity. The BEA also precisely controls and maintains the temperature at 37 °C ± 0.1 °C in the dual-channel assay. We assessed the responses of this system within a clinically relevant range by testing blood samples from a local hospital. The test verified that BEA for ALT and AST achieved a detection limit of 3.5 U L-1 and 4 U L-1, detection range of 4-350 U L-1 and 4-250 U L-1, coefficients of variation (CV) that were both less than 10%, and a linear correlation coefficient of 0.9827 and 0.9714 compared with a high-precision clinical biochemistry analyzer (Roche Cobas C702), respectively. We realized remote data analysis and storage through connection with smartphones, which can be applied to remote diagnostics and preventative personal disease management. Therefore, BEA has broad application prospects in the future internet of medical things.

[Effects of Li-Dan-He-Ji on regulating oxidative stress and antagonising infantile cholestatic hepatic fibrosis].

OBJECTIVE: To explore the clinical effect of Li-Dan-He-Ji in the treatment of infantile cholestatic hepatic fibrosis. METHODS: Patients who met the diagnostic criteria of infantile cholestatic hepatic fibrosis in the department of integrated traditional Chinese and Western medicine and the department of gastroenterology of Wuhan Children's Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January to December 2021 were included in the study by prospective randomized controlled trial. They were divided into the conventional treatment group and Li-Dan-He-Ji group according to the random number table. The patients in the conventional treatment group were given conventional treatment according to the guidelines. In the Li-Dan-He-Ji group, the self-made Chinese medicinal compound Li-Dan-He-Ji (prescription: Herba Artemisiae Scopariae, Fructus Forsythiae, Radix et Rhizoma Rhei preparata, Radix Polygoni Multiflori Preparata, Radix Paeoniae Rubra, Ramulus Cinnamomi, Fructus Aurantii, Rhizoma Atractylodis Macrocephalae, Fructus Schisandrae Chinensis, Carapax Trionycis, and Radix Glycyrrhizae) was given on the basis of the routine treatment, by oral, enema or nasal feeding, 60 mL each day, divided into 2 or 3 times, for 28 days. Outpatient follow-up was maintained for 4 weeks. Before and after treatment, serum liver fibrosis 4 items [type IV collagen (IV-C), hyaluronidase (HA), type III procollagen (PC III), laminin (LN)], liver function and cholestasis-related markers [total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH)], liver stiffness measurement (LSM) detected by transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and liver and spleen retraction time were recorded in the two groups. RESULTS: During the observation period, a total of 40 cases of cholestatic hepatic fibrosis were treated, including 21 cases in the conventional treatment group and 19 cases in the Li-Dan-He-Ji group. Before treatment, the differences in serum liver fibrosis 4 items, serum liver function and cholestasis-related markers, oxidative stress indexes, LSM and APRI of the two groups were not statistically significant. After treatment, the liver fibrosis 4 items, liver function and cholestasis-related markers, LSM, and APRI were all significantly decreased in both groups, and the indexes in the Li-Dan-He-Ji group were significantly lower than those in the conventional treatment group [HA (ng/L): 165.81±21.57 vs. 203.87±25.88, PC III (µg/L): 69.86±9.32 vs. 81.82±7.39, IV-C (µg/L): 204.14±38.97 vs. 239.08±24.93, LN (µg/L): 162.40±17.39 vs. 190.86±15.97, TBil (µmol/L): 37.58±27.63 vs. 53.06±45.09, DBil (µmol/L): 20.55±19.34 vs. 30.08±27.39, ALP (U/L): 436.50±217.58 vs. 469.60±291.69, γ-GGT (U/L): 66.78±35.84 vs. 87.00±32.82, ALT (U/L): 64.75±50.53 vs. 75.20±50.19, AST (U/L): 77.25±54.23 vs. 96.80±59.77, TBA (µmol/L): 74.35±44.44 vs. 85.45±39.50, LSM (kPa): 5.24±0.39 vs. 7.53±3.16, APRI: 0.52±0.39 vs. 0.98±0.29, all P < 0.05]. After treatment, MDA in the two groups were significantly lower than those before treatment, and SOD and GSH were significantly higher than those before treatment. The level of SOD in the Li-Dan-He-Ji group was significantly higher than that in the conventional treatment group (kU/L: 64.56±6.69 vs. 51.58±5.98, P < 0.05). In addition, the liver retraction time (day: 20.13±10.97 vs. 24.33±13.46) and spleen retraction time (day: 25.93±13.01 vs. 29.14±14.52) in the Li-Dan-He-Ji group were significantly shorter than those in the conventional treatment group (both P < 0.05). CONCLUSIONS: The use of Li-Dan-He-Ji in the treatment of cholestatic hepatic fibrosis can effectively improve the indicators of cholestasis, hepatic fibrosis, oxidative stress and clinical symptoms in children.

Salicylic acid protects gentamicin-induced hepatotoxicity: Study in rabbits.

Gentamicin (GM) is a broadly used antibiotic against severe and life-threatening infections, but its efficacy is restricted by the development of liver toxicity. The present study was designed to evaluate the protective effect of salicylic acid (SA) in gentamicin-induced hepatotoxicity in rabbits. Gentamicin and salicylic acid were given at a dose of 80 mg/kg i.p for twenty days. For this purpose, 24 male albino rabbits were randomly divided into four groups. Group I remained untreated and served as control. Group II was given gentamicin, group III was given gentamicin along with Salicylic acid (SA) and group IV was given only salicylic acid. The degree of hepatoprotection was measured by assessment of body weight, liver weight, absolute liver weight and estimations of plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin, tissue malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities. Significant reduction in the elevated liver weight, plasma levels of AST, ALT, bilirubin and tissue MDA and significant elevation in reduced body weight, SOD and CAT activities were found that confirms the protective role of salicylic acid in gentamicin induced hepatotoxicity.

Silymarin, an antioxidant flavonoid, protects the liver from the toxicity of the anticancer drug paclitaxel.

One of the biggest factors that negatively affect the cancer treatment plan is the toxic effects of chemotherapeutics on non-target cells and tissues. This information prompted us to investigate the protective effects of silymarin (SL), a hepatoprotective agent, against the hepatotoxic effects of the anticancer drug paclitaxel (PAC). Four groups were formed from 28 rats as control, PAC (2 mg/kg), SL (100 mg/kg) and PAC + SL (combination of PAC with SL). After completing the experimental procedures, the tissues collected after anesthesia were analyzed by Western blot, qRT-PCR, biochemical, stereological, immunohistochemical, and histopathological techniques. Administration of PAC significantly increased the expression of tumor necrosis factor-alpha (TNF-α), Bax, cytochrome-c (cyt-c), and active caspase-3, as well as malondialdehyde (MDA) levels in liver tissue and decreased glutathione (GSH) levels compared with the control group. PAC also resulted in a significant increase in serum triglyceride (TG), cholesterol (CH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the control group. Pathological changes such as microvesicular steatosis, the formation of Councilman bodies, an increase in total sinusoidal volume, and a decrease in the total number of hepatocytes were observed in the liver tissue of the PAC group. Almost all analysis results in the PAC + SL group were similar to those in the control group, and no significant pathological alterations were observed in this group. The data obtained show that SL protects the liver from the harmful effects of PAC, especially thanks to its TNF-α suppressor, anti-inflammatory, anti-apoptotic and antioxidant effects. Based on this result, in cases where PAC is used in cancer treatment, it can be recommended to be used together with SL to prevent harmful effects on healthy liver tissue and to continue treatment uninterruptedly and effectively.

Phytochemicals from Anneslea fragrans Wall. and Their Hepatoprotective and Anti-Inflammatory Activities.

Anneslea fragrans Wall., popularly known as "Pangpo tea", is an edible, medicinal, and ornamental plant of the Family Theaceae. The leaves of A. fragrans were historically applied for the treatment of liver and intestinal inflammatory diseases in China. This study aimed to explore the hepatoprotective agents from A. fragrans leaves through hepatoprotective and anti-inflammatory assessment. The phytochemical investigation of the leaves of A. fragrans resulted in the isolation and identification of a total of 18 chemical compounds, including triterpenoids, aliphatic alcohol, dihydrochalcones, chalcones, flavanols, phenolic glycoside, and lignans. Compounds 1-2, 4-6, 11-12, and 16-18 were identified from A. fragrans for the first time. Compounds 7 and 14 could significantly alleviate hepatocellular damage by decreasing the contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and inhibit the hepatocellular apoptosis in the HepG2 cells induced by N-acetyl-p-aminophenol (APAP). In addition, compounds 7 and 14 inhibited reactive oxygen species (ROS) and malondialdehyde (MDA) contents and increased the catalase (CAT) superoxide dismutase (SOD), and glutathione (GSH) levels for suppressing APAP-induced oxidative stress. Additionally, compounds 7, 13, and 14 also had significant anti-inflammatory effects by inhibiting interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) productions on LPS-induced RAW246.7 cells.

Swertia bimaculata moderated liver damage in mice by regulating intestine microbiota.

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.

Mitochondrial Lipid Peroxidation and Microsomal Drug-metabolizing Enzyme Activity of Rat Hepatotoxicity under Heavy Metals from Slag Waste Exposure.

Heavy metals from slag waste (HMSWs) have attracted much attention because of their serious toxicity to the environment and human organs, especially hepatotoxicity. The aim of this study was to explore the effects of different HMSWs exposure on mitochondrial lipid peroxidation, microsomal drug metabolizing enzyme activities as well as their relationship in the rat liver injury. Based on toxicogenomic analysis, heavy metals including iron, copper, cobalt, nickel and manganese, might interfere with pathophysiological processes such as oxidative stress, cell death, and energy metabolism regulation in vivo, and participate in the regulation of HIF-1 signaling pathway, peroxisomes, drug metabolism-cytochrome P450, ferroptosis, and other signaling pathways. HMSWs exposure caused weight loss, and significantly increased lactate dehydrogenase (LDH), malondialdehyde (MDA), alanine transaminase (ALT), and aspartate transaminase (AST) in different groups of rat liver, suggesting the presence of mitochondrial lipid peroxidation damage. In addition, the ratios of AST/ALT and ALT/LDH were down-regulated, especially the ALT/LDH ratios were less than 1, indicating that hepatic ischemic injury occurred in the process of liver injury. The superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) activities in rats also showed significant decreases, indicating the occurrence of hepatic oxidative/antioxidant dysfunction imbalance. Further decision tree analysis of live biochemical abnormalities suggested that AST > 58.78 U/gprot and MDA > 173.2 nmol/mgprot could be used for hepatotoxicity warning. Liver microsomal cytochrome P4501A2 (CYP1A2) and 3A1 (CYP3A1) enzymes were also involved in the hepatotoxic process of heavy metals. These results suggest that lipid peroxidation damage and metabolic damage in liver mitochondria and peroxisomes, may be one of the key events in heavy metal-induced liver injury.

Liver Function in Patients with Long-Term Coronavirus Disease 2019 of up to 20 Months: A Cross-Sectional Study.

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.

Protective effect of Lactiplantibacillus pentosus CQZC01 in Kunming mice of subacute alcoholic liver injury.

To decrease the climbing rate of alcoholic liver disease, the protective effect in subacute alcoholic liver injury of newly isolated Lactiplantibacillus pentosus CQZC01 has been investigated. Lactiplantibacillus pentosus CQZC01 (1 × 109 CFU/kgbw) administered orally could keep weight of mice at 30.54 ± 1.15 g; alleviate alcoholic damage on hepatic morphology; decrease the activities of hyaluronidase (147 ± 19 U/L), procollagen III (4.82 ± 0.54 ng/mL), alanine transaminase (10.66 ± 2.32 U/L), and aspartate aminotransferase (15.18 ± 1.98 U/L); enhance the activities of alcohol dehydrogenase (65.15 ± 3.2 U/mgprot), aldehyde dehydrogenase (16.50 ± 0.96 U/mgprot), superoxide dismutase (623 ± 39 U/mgprot), and glutathione (19.54 ± 2.46 µmol/gprot); and decrease liver total cholesterol (3.59 ± 0.50 mmol/gprot) and triglyceride (0.88 ± 0.24 mmol/gprot) (p < 0.05). Moreover, L. pentosus CQZC01 elevated the level of interleukin-10 (IL-10; 807 ± 44 pg/mL) but significantly decreased the levels of IL-1ß (29.75 ± 5.27pg/mL), IL-6 (58 ± 8 pg/mL), and tumor necrosis factor-α (TNF-α, 564 ± 13 pg/mL). Liver malondialdehyde was also significantly decreased by treatment with L. pentosus CQZC01 from 3.61 ± 0.14  to 2.03 ± 0.49 nmol/mgprot. The relative expression of C-Jun N-terminal kinase, extracellular regulated protein kinases, and cyclooxygenase-1 was downregulated, and the SOD1, SOD2, peroxisome proliferator-activated receptor-α, glutathione peroxidase, catalase, nuclear factor erythroid-2-related factor 2, heme oxygenase-1 and nicotinamide adenine dinucleotide phosphate were upregulated by L. pentosus CQZC01. The overall protective effect of L. pentosus CQZC01 was comparable to commercial Lactobacillus delbrueckii subsp. Bulgaricus. Lactobacillus pentosus CQZC01 might be a suitable hepatoprotective measure for people who frequently ingest alcoholic drinks. PRACTICAL APPLICATION: L. pentosus CQZC01 can alleviate subacute alcoholic liver injury by raising the antioxidant status and upregulating the antioxidant-related genes.

Protective effect of glutamic-oxaloacetic transaminase on hippocampal neurons in Alzheimer's disease using model mice.

Alzheimer's disease (AD), a neurodegenerative disease affecting the elderly, frequently causes cognitive impairment and memory decline, and there are currently no effective therapeutic drugs available. Glutamate excitotoxicity is one of the pathogeneses of AD, and there is evidence that glutamic-oxaloacetic transaminase (GOT) can significantly reduce glutamate concentrations in the hippocampi of mice, but its role in APP/PS1 transgenic mice is unknown. We investigated the improvement of neurological function and related protein expression following subcutaneous injection of GOT in mice with AD. We performed immunohistochemical staining on the brain tissue of 3-, 6-, and 12-month-old mice and found that the content of the ß-amyloid protein Aß1-42 in the 6 months old GOT treatment group was significantly reduced. Meanwhile, the APP-GOT group outperformed the APP group in the water maze and spatial object recognition experiments. The number of neurons in the hippocampal CA1 area of the APP-GOT group increased when compared to the APP group according to Nissl staining. Electron microscopic examination of the hippocampal CA1 area demonstrated that the number of synapses in the APP-GOT group was more than that in the APP group, and the mitochondrial structure was relatively complete. Finally, the protein content of the hippocampus was detected. In comparison to the APP group, SIRT1 content increased in the APP-GOT group whereas Aß1-42 content decreased, and Ex527 could reverse this trend. These results suggest that GOT can significantly improve the cognitive function of mice in the early stage of AD, and the underlying mechanism may be through decreasing Aß1-42 and increasing SIRT1 expressions.

Isolation and functional verification of an aspartate aminotransferase gene from Neoporphyra haitanensis.

BACKGROUND: Neoporphyra haitanensis is a commercial laver species in China. Aspartic acid is an important flavor amino acid, and aspartate aminotransferase (AAT) is a crucial enzyme in its biosynthesis. In this study, we cloned one AAT gene (NhAAT) from the red alga N. haitanensis and investigated its sequence structure, transcriptional expression and enzymatic characteristics. The purpose of our research is to obtain a functional AAT responsible for the biosynthesis of aspartic acid from red seaweeds, which has the potential to influence the flavor of N. haitanensis. RESULTS: Sequence analysis showed that NhAAT contains a conserved domain of Aminotran_1_2, which belongs to the transaminase superfamily. The secondary structure of NhAAT is dominated by α-helix. The results of enzymatic characterization illustrated that the NhAAT has highest catalytic activity at 45 °C and pH 7.5 in both forward and reverse reactions. The calculated Km values of NhAAT was 5.67 and 6.16 mM for L-glutamic acid and L-aspartic acid, respectively. Quantitative analysis showed that the NhAAT expression of N. haitanensis collected in late harvest (Dec) was 4.5 times that of N. haitanensis collected in early harvest (Oct), while the aspartic acid content of N. haitanensis collected in late harvest (Dec) was 1.2 times that of N. haitanensis collected in early harvest (Oct). CONCLUSION: The results of enzyme kinetics indicated that NhAAT prefers to catalyze the reaction in the direction of aspartic acid production. Moreover, the trend of NhAAT expression level was consistent with that of aspartic acid content in N. haitanensis in different harvest periods. Our research is helpful to understand the accumulation and regulation of amino acids in N. haitanensis in different habitats and the taste difference of N. haitanensis in different harvest periods.