Aminotransferase Activity Research Articles

Ajuga iva extract lowers plasma cholesterol and improves lipoprotein profile and lecithin: cholesterol acyltransferase (LCAT) activity in rats fed high cholesterol diet

The purpose of the study was to investigate the therapeutic and preventive effects of Ajuga iva (L) Schreber (Labiatae) (Ai) extract on hypercholesterolemic model rats. For this aim, male Wistar rats were fed a high‑cholesterol (1%) diet to establish a hypercholesterolemia model supplemented or not with aqueous extract of Ajuga Iva (Ai) (5 g/kg diet) for 4 weeks. Ai lowered plasma total cholesterol (TC) (18%) with a reduction in cholesteryl esters (CE) (29%). Low VLDL-TC and high HDL2-TC were observed in Ai group. TC/HDL’s -C ratio was 1.64-fold lower, whereas HDL’s-C/ LDL-HDL1-C was 1.82-fold higher in Ai treated rats. Triacylglycerols (TG) were reduced in plasma and in VLDL but increased in HDL2 and HDL3 with Ai supplementation. Rats exposed to Ai diet lowered VLDL-unesterified cholesterol (UC), LDL-HDL1-amount and LDL-HDL1-CE but increased HDL3-CE. Low levels of liver phospholipids (PL) and high CE concentrations were observed in Ai group. In aorta, TC was decreased by 37% with Ai. Feeding Ai diet decreased HDL3-PL and increased HDL2-CE and plasma LCAT activity. Moreover, Ai administration (5 g/kg for 4 weeks) improved liver and kidney function, as demonstrated by decreased plasma aspartate aminotransferase (AST) activity and creatinine, and resulted in an increase of urinary and sodium excretion. We conclude that, in addition to its Strong C and TG-lowering effect, Ai improves effectively the atherogenic lipoproteins profile by reducing the LDL-HDL1 amount and increasing the HDL-cholesterol. Furthermore, Ai increases the reverse cholesterol transport by enhancement of cholesterol: acyltransferase (LCAT) activity. These beneficial effects are considered potential mechanisms through which Ai acts as a protective agent against cholesterol-induced damage, ensuring cardiovascular safety.

Bovine Lung Peptides after Trypsinolysis Reveal Anti-Exudative Activity

Abstract Enzymatic hydrolysates of proteins isolated from cow lungs are used as anti-inflammatory agents for the growth and regeneration of new tissues. Hydrolysates were observed to inhibit the production of free radicals in cells and have a high anti-exudative activity even in low doses. In this study, we established the anti-exudative activity of peptides of protein hydrolysates isolated from bovine lungs. The anti-exudative activity of the peptides sum was compared with acetylsalicylic acid (ASA) and prednisolone, and the dynamics of inflammation were studied by tumour formation using carrageenan and formalin. Between 1 h and 24 h after administration of the drug, the effect of the peptides sum showed a significantly better indicator than the rest of the means. In general, the anti-exudative activity of the peptides sum was 2–3 times higher than the rest of the preparations. Biochemical indicators of prednisolone and peptides sum in two doses of 10−6 μg/kg and 10−4 μg/kg were studied. As a result of the study, it was found that the peptides sum at 10−6 μg/kg dose enhanced alanine aminotransferase (ALT) activity by 17.1% compared to those resulting from prednisolone treatment. In C-reactive protein (CRP) and antistreptolysin O (ASO) indicators, 10−4 μg/kg dose showed high activity. The sum of isolated peptides reduced ALT and ASO levels. This study provides additional support for preparing anti-inflammatory means from the peptides sum isolated from bovine lungs.

Necroptosis contributes to deoxynivalenol-induced liver injury and inflammation in weaned piglets

BackgroundThe aim of this study was to investigate the role of necroptosis in deoxynivalenol (DON)-induced liver injury and inflammation in weaned piglets.MethodsIn Exp. 1, 12 weaned piglets were divided into 2 groups including pigs fed basal diet and pigs fed diet contaminated with 4 mg/kg DON for 21 d. In Exp. 2, 12 weaned piglets were divided into 2 groups including control piglets and piglets given a gavage of 2 mg/kg body weight (BW) DON. In Exp. 3, 24 weaned piglets were used in a 2 × 2 factorial design and the main factors including necrostatin-1 (Nec-1) (DMSO or 0.5 mg/kg BW Nec-1) and DON challenge (saline or 2 mg/kg BW DON gavage). On 21 d in Exp. 1, or at 6 h post DON gavage in Exp. 2 and 3, pigs were killed for blood samples and liver tissues. Liver histology, blood biochemical indicators, and liver inflammation and necroptosis signals were tested.ResultsDietary or oral gavage with DON caused liver morphological damage in piglets. Dietary DON led to hepatocyte damage indicated by increased aspartate transaminase (AST) activity and AST/alanine aminotransferase (ALT) ratio, and DON gavage also caused hepatocyte damage and cholestasis indicated by increased AST and alkaline phosphatase (AKP) activities. Dietary DON caused liver necroptosis indicated by increased protein abundance of total receptor interacting protein kinase 3 (t-RIP3) and total mixed lineage kinase domain-like protein (t-MLKL). Moreover, DON gavage increased mRNA expression of interleukin (IL)-6 and IL-1β in liver. DON gavage also induced liver necroptosis demonstrated by increased protein abundance of t-RIP3, phosphorylated-RIP3 (p-RIP3), t-MLKL and p-MLKL. However, pretreatment with Nec-1, a specific inhibitor of necroptosis, inhibited liver necroptosis indicated by decreased protein expression of t-RIP3, p-RIP3, t-MLKL and p-MLKL. Nec-1 pretreatment reduced liver morphological damage after DON gavage. Pretreatment with Nec-1 also attenuated liver damage induced by DON indicated by decreased activities of AST and AKP. Furthermore, Nec-1 pretreatment inhibited liver mRNA expression of IL-6 and IL-1β after DON challenge.ConclusionsOur data demonstrate for the first time that necroptosis contributes to DON-induced liver injury and inflammation in piglets.

Modulation of cadmium-induced nephrotoxicity by iron supplementation in rats

Cadmium is known to cause nephrotoxicity in rats. This research aimed to evaluate the influence of iron on cadmium toxicity when rats were exposed to water and food-chain-mediated feed. Twenty-four rats were divided into four groups containing three rats for the two-phase studies. After four weeks of exposure, the rat’s kidney was excised and evaluated for a kidney function test involving alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. In rats exposed via water, Cd-exposed rats show a significantly increased ALT level (266.250 ± 0.005U/I) compared to the control group (238.321 ± 0.0001U/I) while Fe-exposed rats exhibit a significant decrease in ALT levels (182.972 ± 0.029U/I) compared to the control group. Cd+Fe-exposed rats show a further significant decrease in ALT levels compared to both the control and other experimental groups. Also, Cd-exposed rats show a significant decrease in AST levels (200.176 ± 0.018U/I) compared to the control group (287.108 ± 0.003 U/I) while Fe-exposed rats do not show a significant difference in AST levels (277.553 ± 0.448U/I) compared to the control. In rats exposed via feeding, Cd-exposed rats show decreased ALT levels (159.868 ± 0.132U/I) compared to the control group (179. 076 ± 0.001U/I) while Cd+Fe-exposed rats have ALT levels (178.001 ± 0.001U/I) almost identical to the control group, indicating that the combined exposure to Cd and Fe might neutralize the individual effects on ALT levels. The results revealed that iron offers protection against cadmium-induced toxicity in the kidney. This finding suggests that cadmium toxicity in the kidney could be ameliorated in the presence of iron, potentially opening new and promising avenues for the prevention and treatment of cadmium toxicity in humans. This is a finding of direct relevance to the fields of biochemistry and environmental science, and it brings hope for the future of cadmium toxicity research.

Physiological and biochemical responses of Labeo rohita to neonicotinoids imidacloprid, clothianidin, and their mixture.

Neonicotinoids, widely used insecticides, pose severe environmental risks due to their persistence in soil and water, adversely affecting non-target organisms and ecosystem integrity. The present study examined the 56days effects of imidacloprid (66.6mg/l), clothianidin (30mg/l), and their combination (33.3mg/l and 15mg/l) on Labeo rohita, using one-third of the LC50 sub-lethal concentrations. Survival, weight gain, and the hepatosomatic index decreased insignificantly in the IMI group and significantly in the CLO and Mix groups. Haematological indicators, including erythrocyte counts, haemoglobin, and haematocrit values, were also significantly reduced. Blood glucose and serum creatinine levels increased, while serum albumin, globulin, and plasma total proteins decreased. White blood cell counts elevated, while immunoglobulin (IgM), respiratory burst, and lysozyme activities were significantly inhibited. Liver, brain and muscle lactate and malate dehydrogenases were elevated, whereas succinate and glutamate dehydrogenases were decreased. Liver aspartate aminotransferase activity was substantially higher than that of brain and muscle, which had considerably higher levels of alanine aminotransferase in muscle than in the brain and liver. Additionally, muscle alkaline phosphatase activity was significantly higher than in the liver and brain, whereas liver acid phosphatase showed a greater elevation than in the muscle and brain. The physiological, haematological, and biochemical indices peaked on day 28 and slight recovery was observed on day 56 (IMI > CLO > Mix). The study highlights that the mixture of insecticides poses greater hazards compared to a single active compound, and the indiscriminate use of these insecticides jeopardizes non-target organisms, ecosystems, and public health.

Crystal structure of a novel heterooligomeric aminotransferase from Serratia sp. ATCC 39006 provides insights into function.

Serratia sp. ATCC 39006 has two tandemly positioned genes, ser4 and ser5, both annotated as sugar aminotransferases, in a putative secondary metabolite biosynthetic gene cluster. Ser5 possesses a complete fold-type I aminotransferase fold, while Ser4 lacks the N- and C-terminal regions and a catalytically important lysine residue of fold-type I aminotransferase. We herein revealed that Ser4 and Ser5 formed a heterotetrameric complex (SerTA) with aminotransferase activity and determined the crystal structures. MD simulations and activity assays with SerTA variants indicated that residues from helix α-8* of inactive Ser4 are important for activity, confirming the importance of heterocomplex formation for activity. Furthermore, the structures suggest that SerTA recognizes a substrate loaded on the carrier protein.

Molecular pathways of osmoregulation in response to salinity stress in the gills of the scalloped spiny lobster (Panulirus homarus) within survival salinity

Scalloped spiny lobster (Panulirus homarus) aquaculture is the preferred strategy to resolve the conflict between supply and demand for lobster. Environmental conditions, such as salinity, are key to the success of lobster aquaculture. However, physiological responses of P. homarus to salinity stress have not been well studied. This study investigated the gill histology, osmoregulation and gill transcriptome of the early juvenile P. homarus (weight 19.04 ± 3.95 g) cultured at salinity 28 (control), 18, and 38 for 6 weeks. The results showed that the gill filaments of P. homarus exposed to low salinity showed severe separation of the cuticle and epithelial cells due to water absorption and swelling, as well as the dissolution and thinning of the cuticle and the rupture of the septum that separates the afferent and efferent channels. The serum osmolarity of P. homarus varied proportionately with external medium salinity and remained consistently above ambient osmolarity. The serum Na+, Cl−, K+, and Mg2+ concentrations P. homarus exhibited a pattern similar to that of serum osmolality, while the concentration of Ca2+ remained unaffected at salinity 18 but significantly increased at salinity 38. Gill Na+/K+-ATPase activity of P. homarus increased (p < 0.05) under the both salinity stress. Salinity 18 significantly increased Glutamate dehydrogenase (GDH) and Glutamicpyruvic transaminase (GPT) activity in the hepatopancreas of P. homarus (p < 0.05). According to transcriptome analysis, versus control group (salinity 28), 929 and 1095 differentially expressed genes (DEGs) were obtained in the gills of P. homarus at salinity 18 and 38, respectively, with these DEGs were mainly involved in energy metabolism, transmembrane transport and oxidative stress and substance metabolism. In addition, the expression patterns of 8 key DEGs mainly related to amino acid metabolism, transmembrane transport and oxidative stress were verified by quantitative real-time PCR (RT-qPCR). The present study suggests that salinity 18 has a greater impact on P. homarus than salinity 38, and P. homarus demonstrates effective osmoregulation and handle with salinity fluctuations (18 to 38) through physiological and functional adaptations. This study provides an improved understanding of the physiological response strategies of P. homarus facing salinity stress, which is crucial for optimizing aquaculture practices for this species.

Methionine and vitamin E supplementation improve production performance, antioxidant potential, and liver health in aged laying hens

Sulfur metabolites of methionine (Met) and vitamin E (VE) have antioxidant potential and can maintain liver health in chickens. This study explored the underlying mechanisms of Met sources, the ratio of total sulfur amino acids to lysine (TSAA: Lys), and VE levels on production performances, antioxidant potential, and hepatic oxidation in aged laying hens. Eight hundred and sixty-four, Hy-Line Brown laying hens (70-week age) were divided into 12 treatment groups, each having 6 repeats and 12 birds/each repeat. The dietary treatments consisted of DL-Met (DL-Met), DL-2-hydroxy-4-(methylthio)-butanoic acid (OH-Met), 3 ratios of TSAA: Lys (0.90, 0.95, and 1.00), and 2 levels of VE (20 and 40 g/ton). Albumen height and Haugh unit significantly increased at a lower level of VE (P < 0.05). Triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) in serum and superoxide dismutase (SOD) and catalase activities (CAT) in the liver significantly reduced at 0.95 TSAA: Lys ratio (P < 0.05). Fatty acid synthase (FAS), lipoprotein lipase (LPL), nuclear factor erythroid 2-related factor 2 (Nrf2), and carnitine palmitoyltransferase-1 alpha (CPT-1α) also upregulated at this TSAA: Lys ratio (P < 0.05). Compared with the DL-Met group, the OH-Met group had lower Dipeptidyl Peptidase 4 (DPP4) and higher TC, LDL, and VLDL concentrations (P < 0.05).The expression of FAS,CPT-1α), glutathione (GSH), glutathione disulfide (GSSG), glutathione synthetase (GSS), and Nrf2 were significantly higher in OH-Met compared with the DL-Met group (P < 0.05). OH-Met at 0.95 and DL-Met at 0.90 TSAA: Lys ratio showed higher CAT and lower aspartate aminotransferase (AST) activities. Moreover, OH-Met at 0.90 and DL-Met at 0.95 of the TSAA: Lys ratio had a significant reduction of malondialdehyde (MDA) (P < 0.05). Overall, these results suggest that OH-Met source with a lower level of VE positively influenced production performance and improved liver health in aged laying hens through improved lipid metabolism and hepatic antioxidant function.

Growth, fat metabolism and hepatic health in largemouth bass fed varying fat-level diets

This 60-day experiment investigated the influences of growth, fat metabolism and hepatic health of largemouth bass (Micropterus salmoides) fed varying fat diets. 225 fish (34 ± 0.04 g) were divided into three groups and fed diets with fat levels of 10 % (Low-fat diet, LFD), 14 % (Medium-fat diet, MFD) and 18 % (High-fat diet, HFD), respectively. The results revealed that fish fed HFD exhibited significantly better protein efficiency ratio (PER) and lower feed conversion ratio (FCR) than LFD group (P<0.05), but survival rate (SR) and weight gain rate (WGR) were unaffected (P>0.05). Dietary fat levels significantly decreased hepatosomatic index (HSI) of fish (P<0.05), but visceral somatic index (VSI) and condition factor (CF) were unaffected (P>0.05). The contents of fat and ash in whole-body, and hepatic fat contents were increased with dietary fat levels (P<0.05), the contents of moisture and crude protein in whole-body and liver exhibited no substantial variations (P>0.05). Serum biochemical indexes and serum alanine aminotransferase (ALT) activity, liver glutathione peroxidase (GSH-Px) and catalase (CAT) activities were increased significantly with rising dietary fat levels (P<0.05), serum aspartate transaminase (AST) and liver superoxide dismutase (SOD) activities had no statistical differences (P>0.05). The expression of srebp-1 and acc in liver were down-regulated, but atgl, aco and bax were up-regulated with rising dietary fat contents (P<0.05). Caspase-3 exhibited a remarkable tendency of initially rising and then declining (P<0.05), the expression of fas, cpt-I, bcl-2 and the ratio of bcl-2/bax were unaffected (P>0.05). The histology of liver indicated the size and quantity of fat droplets increased with increment of dietary fat intake. Conclusion: the dietary fat levels of 14 %-18 % could be conducive to better growth of largemouth bass in this study.

The biochemical effects of Kola Nitida on the Liver of Lipid-Induced Wistar Rats

This study investigates the biochemical effects of Kola Nitida on the liver of Wistar rats subjected to a high lipid diet. A High lipid diet induces oxidative stress, inflammation, and pancreatic dysfunction. This study evaluated whether Kola Nitida, known for its bioactive compounds such as flavonoids, caffeine, and theobromine, could protect the liver from lipid-induced damage. The study was conducted within 6 months (April – September 2024). The effect of bioactive compounds from kola nut extracts on liver functions of Wistar rats was investigated using standard methods. Twenty Wistar rats were used for the study. They were randomly divided into five groups 1, 2, 3, control, and toxicity made up of 4 rats each. The control group received water food, Group 1 received kola nitida extract 100mg/kg body weight water food, group (B) received kola nitida extract 200mg/kg body weight water food, and Group (C) received kola nitida extract 300mg/kg body weight water food by oral administration for 14 days. The results showed that caffeine from kola nuts had effects on the liver functions of the Wistar rats. Administration of kola nitida (vera) significantly decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), GGT, Total bilirubin (TB), Total protein (TP), Albumin (ALB), activities, consumption of HFD increased total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)activity. Body weight, organ weight, and histopathological study were significantly reduced. This study seems to suggest that consumption of HFD and reversal with kolanut (kola nitida) will significantly cause positive effects on the biological and histological liver functions of humans.

Hematology, Plasma Biochemistry, Protein Electrophoresis, and Pathogen Surveillance in Headstarted and Wild-Reared Populations of Blanding's Turtles (Emydoidea blandingii) in Three Northern Illinois, USA, Counties.

Blanding's turtles (Emydoidea blandingii) are a species of conservation concern throughout their natural range. Headstarting is a common chelonian conservation technique in which neonates are reared in managed-care settings before release, but health assessments are rarely incorporated. From 2020 to 2021 we assessed headstarted turtle health pre-release and 1 mo, 1 yr, and 2 yr after release using physical examination, hematology, plasma biochemistry, protein electrophoresis, and pathogen detection. Results were compared to wild-reared juveniles in the same habitats. Overall, 767 assessments from 561 turtles were included. Wild-reared and 2 yr post-release headstarts had higher incidence of hemoparasites, asymmetrical nares, and increased creatine kinase and aspartate aminotransferase activities (P<0.05) compared to all other groups. Erythrocyte sedimentation rate and heterophil:lymphocyte ratio were greater, while total leukocyte and lymphocyte counts were lower (P<0.05) in pre-release headstarts compared to wild-reared juveniles. Total solids, albumin, and beta globulins were higher, while the calcium:phosphorous ratio was lower (P<0.05) in pre-release headstarts and wild-reared juveniles vs. other groups. Bile acid levels were highest in pre-release headstarts (P<0.05). Body condition and gamma globulins increased following release, while alpha globulins and the albumin:globulin ratio decreased following release (P<0.05). Two pre-release and one post-release headstart tested positive for Emydomyces testavorans, one post-release headstart was positive for Mycoplasmopsis sp., and nine post-release turtles were positive for adenoviruses. Overall, rearing conditions have a profound and temporally dynamic impact on Blanding's health assessment parameters. Future studies should evaluate long-term impacts on morbidity and mortality to support positive health status and conservation outcomes.

Study on the mechanism of Fuzheng Huayu formula against biliary fibrosis in mice

Objective: To investigate the effect and mechanisms of Fuzheng huayu formula (FZHY) on biliary fibrosis in mice. Methods: Mdr2 gene knowout (Mdr2-/-) mice were randomly divided into model group, FZHY-treated group and obeticholic acid (OCA)-treated group. Wide type C57BL/6J (WT) mice of the same age were used as the control group. Mdr2-/- mice were treated with the corresponding drugs by gavage from the first day of the 9th week old. The WT and model groups were given 0.3% sodium carboxymethyl cellulose by gavage, and the mice were sacrificed at the end of 12th week old. The activities of serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were detected by high-speed biochemical analyzer. H&E staining and sirius red staining were used to observe the pathological changes of liver tissues. The hepatic hydroxyproline content was determined. The hepatic expressions of Col-Ⅰ and α-SMA, ductular reaction markers Epcam, CK7, CK19, and the expression of Pcna, Mki67 and Ccnd1; as well as the expression of inflammatory cytokines Ccl2, Ccl5, Tnf-α, Il10 and Cxcl4 were detected by immunohistochemical staining, western blot and qRT-PCR, respectively. Furthermore, the expression of PPARα and the phosphorylation NF-κB were detected by western blot. Results: Compared with WT mice, the serum ALT and ALP activities of Mdr2-/- mice were significantly increased (P<0.001). The percentage of SR positive stained area and hepatic Hyp content were significantly increased (P<0.01). The hepatic expression of Col-Ⅰ and α-SMA; Epcam, CK7, CK19, Pcna, Mki67 and Ccnd1; Ccl2, Ccl5, Tnf-α, Il10 and Cxcl4 were significantly increased (P<0.01). However, both FZHY and OCA significantly reversed the elevation of these aforementioned indicators (P<0.05; P<0.01). Further study showed that the hepatic expression of PPARα in Mdr2-/- mice was significantly lower than that of WT mice, however the phosphorylation of NF-κB was significantly enhanced (P<0.01). The expression of PPARα in liver tissues of FZHY mice was significantly increased (P<0.05), and the NF-κB phosphorylation was significantly inhibited compared with Mdr2-/- mice (P<0.05). Conclusion: FZHY significantly ameliorated liver fibrosis, ductular reaction and inflammation in Mdr2-/- spontaneous biliary fibrosis mice, and its mechanism was related to the regulation of PPARα/NF-κB pathway.

Effects of Transport Stress (Duration and Density) on the Physiological Conditions of Marbled Rockfish (Sebastiscus marmoratus, Cuvier 1829) Juveniles and Water Quality

Live transportation is a critical component of fish farming and hatchery release. To optimize hatchery-release techniques and improve the survival rate of marbled rockfish (Sebastiscus marmoratus, Cuvier 1829) juveniles, the effects of varying transport durations (2, 4, 6, and 8 h) and densities (60, 90, 120, and 150 kg m−3) on the physiological indicators of the fish and water quality were investigated under controlled laboratory conditions. We found that as transport duration and density increased, water quality significantly deteriorated, with ammonia nitrogen levels rising and dissolved oxygen content and pH levels decreasing. Physiological indicators including levels of lactate, cortisol, and malondialdehyde and activities of superoxide dismutase, alkaline phosphatase, and glutamate oxaloacetate transaminase notably increased, indicating that the fish experienced heightened stress during transport. Additionally, the mortality rate of juveniles increased significantly with increasing density and transport duration. The high mortality rate might be associated with sustained elevated cortisol levels and liver damage. Our results are helpful for determining the optimal transport conditions for S. marmoratus juveniles and also provide valuable insights for improving transport techniques for other aquatic animal species.

Plasma chemistry and hematology of Eastern Mediterranean Sea green turtles undergoing rehabilitation

Plasma chemistry and hematology of Eastern Mediterranean Sea green turtles undergoing rehabilitation

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

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

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

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

LsMYB44 and LsWRKY12 regulate endogenous γ-aminobutyric acid (GABA) accumulation in fresh-cut stem lettuce

GABA is able to increase resistance to biotic and abiotic stresses in fresh-cut fruits and vegetables. Therefore, the objective of this research was to explore the potential regulatory mechanisms of γ-aminobutyric acid (GABA) accumulation in fresh-cut stem lettuce following GABA treatment. The evidence showed that exogenous GABA stimulated the GABA shunt by elevating glutamate levels, the activities of GABA transaminase (GABA-T) and glutamate decarboxylase (GAD). Similarly, GABA stimulated polyamine metabolism by increasing the activities of 4-amino aldehyde dehydrogenase (AMADH), polyamine oxidase (PAO) and diamine oxidase (DAO), as well as elevating free polyamines, arginine and ornithine levels. Subsequently, GABA application up-regulated the expression of GABA shunt genes and polyamine metabolism genes. Additionally, GABA treatment resulted in the down-regulation of LsMYB44 and LsWRKY12 expressions. Notably, LsMYB44 bound to MYB binding sites in the LsGAD, LsGABAT1, LsADC1, LsPAO2, LsALDH7B4 promoters and repressed transcription of these genes. The interaction between LsMYB44 and LsWRKY12 was associated with the transcriptional repression of polyamine metabolism and GABA shunt genes by LsMYB44. In conclusion, LsMYB44 and LsWRKY12 downregulated the transcription of key genes of GABA shunt and polyamine metabolism in fresh-cut lettuce. This downregulation, however, was alleviated by the application of GABA, thereby promoting endogenous GABA accumulation.

Chronic hyperglycemia induces hepatocyte pyroptosis via Gα12/Gα13-associated endoplasmic reticulum stress: Effect of pharmacological intervention

AimsHyperglycemia induces pathophysiological changes. Endoplasmic reticulum (ER) stress with Gα12 overexpression may promote hepatocyte death. This study investigated whether sustained hyperglycemia triggers ER stress-associated pyroptosis and fibrosis in the liver alongside an overexpression of Gα12, and examined the potential link with VEGF-A levels. Main methodsMice were subjected to a high-fat diet (60 kcal% fat) with streptozotocin (50 mg/kg body weight, three consecutive times, between 12‐13th weeks). AZ2 (a functional Gα12 inhibitor) was treated at 10 mg/kg body weight (5 times/week, 3 weeks). Immunoblotting and immunohistochemistry analyses were performed. Key findingsHepatic Gα12/Gα13 were overexpressed in the diabetic mice. The following proteins downstream from the Gα12 axis were upregulated: PGC1α, PPARα, and SIRT1. Sustained hyperglycemia promoted ER stress marker levels. Histopathological and biochemical assays showed large-sized lipid droplet accumulation, hepatocyte degeneration, and damage as blood transaminase activities increased. Moreover, the diabetic condition increased IL-1β, caspase-1, and NLRP3 levels, which were supportive of pyroptosis. Consistently, the intensities of Masson's trichrome, collagen-1A1, α-SMA, vimentin, and fibronectin all increased. VEGF-A and VEGFR2 levels also increased in the liver and/or sera. The levels of hepatic pigment epithelial-derived factor (PEDF), a physiological antagonist of VEGF-A, decreased with its reciprocal increase in serum. These events were reversed by AZ2 treatment, supporting the role of Gα12 in hyperglycemic stress in the liver. SignificanceChronic hyperglycemia causes hepatic pyroptosis and fibrosis related to ER stress with Gα12/Gα13 and VEGF overexpression, which may be overcome by AZ2 treatments.

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

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

Integrated physiological, energy metabolism, and metabonomic responses indicate the stress response in the hepatopancreas of Litopenaeus vannamei to nitrite stress

Nitrite is a toxic substance found in rearing water that affects shrimp health. The hepatopancreas is an important digestive, immune, and metabolic organ in the shrimp. In this study, shrimps (Litopenaeus vannamei) were separately exposed to 1 and 5 mg/L nitrite stress for 48 h, and the toxicity of nitrite in the hepatopancreas was explored by integrating histology, physiological indicators, energy metabolism, and metabolomics. Nitrite stress induced morphological changes and stress responses in the hepatopancreas. Specifically, physiology-related indices, such as the relative gene expression levels of antioxidants (ROMO1, Nrf2, GPx), endoplasmic reticulum stress (Bip, IRE1 and XBP1), and immune genes (ALF, Pen-3, Lys) were decreased, whereas the gene expression of apoptosis (Casp-3), detoxification (CYP450), and glutamic oxaloacetic transaminase (GOT) activity were increased. The activities of osmotic adjustment-related enzymes (NKA, CMA, and ATPase) also decreased. Energy metabolism-related indices, such as pyruvate and hepatic glycogen contents, increased, whereas glucose, lactic acid, triglyceride, and ATP contents and ATPase activity decreased, and the relative gene expression levels of carbohydrate metabolism (PDH, HK, and LDH) and electron-transport chain genes (CytC, COI and CCO) decreased, and the expressions of lipid metabolism (AMPK, SREBP, and FAS), tricarboxylic acid cycle (MDH, CS, IDH and FH) genes were also disturbed. The metabolic pattern of the hepatopancreas was affected by nitrite stress. Glycine, serine, and threonine metabolism were highly affected, and more functional amino acids varied in the 5 mg/L nitrite stress group. These results reveal the toxic effects of nitrite stress on the stress response, physiology, energy metabolism, and metabolite homeostasis in the hepatopancreas of shrimp. Several potential metabolite biomarker candidates were identified for toxicological evaluation.