Serum Aspartate Aminotransferase Activities Research Articles

Orbea variegata (L.) Haw in skin carcinogenesis: insights from an in vivo male Swiss mouse model study

ABSTRACT Skin cancer is the most widespread type of malignant tumor representing a major public health concern. Considering the numerous side effects associated with conventional treatments, phytotherapy may be regarded as a viable medicinal alternative. This study aimed to investigate the therapeutic potential of Orbea variegata (L.) Haw, an ornamental plant, in treating skin cancer using an animal model induced by a combination of ultraviolet (UV) irradiation and sulfuric acid treatment. The hydroethanolic extract of Orbea variegata underwent phytochemical characterization, identifying the presence of reducing sugars, coumarins, alkaloids, flavonoids, tannins, and saponins through qualitative screening. Quantitative analysis demonstrated significant amounts of phenolic compounds (29.435 ± 0.571 mg GAE/g of dry extract), flavonoids (6.711 ± 0.272 mg QE/g of dry extract), and tannins (274.037 ± 11.3 mg CE/g of dry extract). The administration the hydroethanolic extract in two concentrations (1 or 2 g/kg) to male Swiss mice exhibited no marked adverse effects, as evidenced by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activity levels. In addition, the extract significantly reduced skin hyperplasia and inflammation induced by UV/sulfuric acid treatment as noted in tissue analyses and decreased protein expression of nuclear proliferation marker (Ki-67). This improvement was associated with a marked decrease in oxidative stress, as indicated by diminished lipid peroxidation levels, and restoration of the activity of endogenous antioxidant enzyme catalase (CAT) to control levels. Our findings demonstrated the potential of Orbea variegata hydroethanolic extract to be considered as a treatment for skin cancer, exhibiting its apparent safety and efficacy in reducing inflammation and carcinogenesis in a UV/sulfuric acid-induced Swiss mouse model, attributed to its phytochemical content and associated antioxidant activities.

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

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

Hepatoprotective effect of jojoba oil against lead-induced toxicity in rats

Background Previous investigations showed that jojoba oil exhibited a protective effect against hepatotoxicity caused by different toxicants, however, to the best of our knowledge, no prior research has been done to determine the effectiveness of jojoba oil in protecting against lead toxicity. Objective This study assessed the hepatoprotective properties of jojoba oil against lead toxicity in rats. Materials and methods The study included four groups, each consisting of six Sprague Dawley male rats, and orally administered jojoba oil (JO group), lead acetate (LA group), and lead acetate plus jojoba oil (protective group) Results and conclusion The results showed that lead acetate-induced hepatotoxic effects were revealed by increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities with hepatic histomorphological changes. There was a significant increase in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, while levels of high-density lipoprotein-cholesterol significantly declined compared to normal rats. Additionally, lead acetate triggered oxidative damage of hepatocytes, evidenced by a significant increase of malondialdehyde levels and a decrease of reduced glutathione levels and activities of superoxide dismutase and glutathione S-transferase. Administration of lead was associated with a change in the distribution of cells over different cell cycle phases, characterized by a marked increase in the sub G1 cell population and a significant decrease in the G0/G1 cell population. Supplementation of jojoba oil with lead acetate relieved the toxic impacts of lead acetate with an enhancement of the liver enzyme activities, antioxidant status, lipid profile parameters, and histopathological alterations. In conclusion, jojoba oil might be an effective natural product that offers a promising preventive action towards lead-induced liver damage in rats.

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

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

Cymbopogon schoenanthus (L) extract ameliorates high fat diet-induced obesity and dyslipidemia via reducing expression of lipogenic and thermogenic proteins

Globally, obesity has become one of the major health problems. This study was conducted to evaluate the anti-obesity potential of Cymbopogon schoenanthus methanolic extract (CS) in rats. Fifty male Wistar rats of six to eight weeks old, 100–120 g body weight (BW) were randomly assigned into 5 groups (n = 10): The control group was fed a basal diet. CS-group was supplied with basal diet and orally given CS (200 mg/kg BW) for 12 weeks. HFD-group was fed a high-fat diet (HFD) for 18 weeks. HFD + CS-group was fed on HFD and CS HFD then CS-group was fed HFD for 12 weeks then shifted to basal diet and CS for another 6 weeks. Phytochemical analysis of CS indicated the presence of various terpenes and flavonoid compounds. Among the compounds characterized are quercetin, apigenin, luteolin, orientin, eudesmene, cymbopogonol, caffeic acid, coumaric acid, and linolenic acid. Supplementation of HFD significantly increased the body weight, levels of serum triacylglycerol, total cholesterol, very low-density lipoprotein, low-density lipo-protein (HDL), glucose, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. In addition, HFD up-regulated the protein expression of uncoupling protein (UCP)-1 in both brown and white adipose tissue; and the expression of hepatic mRNA of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2. However, it decreased the serum level of HDL, and protein expression level of UCP-1 in both brown and white adipose tissue. Treatment of HFD-fed animals with CS extract either concurrently (HFD + CS-group), or after obesity induction (HFD then CS-group) significantly reversed all HFD-induced alterations in body weight; food intake; serum biochemical profile (including hyperglycemia, dyslipidemia); and tissue gene expressions. These results indicate that CS methanolic extract ameliorated HFD-induced obesity, serum biochemical, hepatic, and adipose tissue gene expression alterations. CS extract accomplished these effects mostly through its various identified bioactive compounds which have been proven to have anti-obesity and anti-diabetic activities.

Inhibiting apoptosis and GSDME-mediated pyroptosis attenuates hepatic injury in septic mice

BackgroundSepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. MethodsAdult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1β, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. ResultsCompared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1β and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1β, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1β and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1β protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). ConclusionApoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.

Effects of Lycium barbarum polysaccharides supplemented to high soybean meal diet on immunity and hepatic health of spotted sea bass Lateolabrax maculatus.

High soybean meal diet (HSBMD) decreased the immunity and damaged the liver health of spotted sea bass; in this study, Lycium barbarum polysaccharides (LBP) was added to HSBMD to explore its effects on the immunity and liver health. The diet with 44% fish meal content was designed as a blank control. On this basis, soybean meal was used to replace 50% fish meal as HSBMD, and LBP was added in HSBMD in gradient (1.0, 1.5, 2.0 g/kg) as the experimental diet. 225-tailed spotted sea bass with initial body weight of 44.52 ± 0.24 g were randomly divided into 5 groups and fed the corresponding diet for 52 days, respectively. The results show that: after ingestion of HSBMD, the immunity of spotted sea bass decreased slightly and hepatic tissue was severely damaged. And the addition of LBP significantly improved the immune capacity and protected the hepatic health. Specifically, the activities of serum lysozyme (LZM), immunoglobulin M (IgM), liver acid phosphatase (ACP) and alkaline phosphatase (AKP) were increased, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly decreased, and hepatic morphology was improved. In the analysis of transcriptome results, it was found that toll-like receptor 3 (TLR3) and toll-like receptor 5 (TLR5) were down-regulated in toll-like receptor signaling pathway. And LBP may protect hepatic health by regulating Glycolysis/Gluconeogenesis, Insulin signaling pathway, Steroid biosynthesis and other glucolipid-related pathways. In conclusion, the addition of LBP in HSBMD can improve the immunity and protect the hepatic health of spotted sea bass, and its mechanism may be related to glucose and lipid metabolism.

Effects of quercetin and hydroxytyrosol supplementation in a high-fat diet on growth, lipid metabolism, and mitochondrial function in spotted seabass (Lateolabrax maculatus)

Endoplasmic reticulum (ER) stress and mitochondrial impairment commonly occur during the progression of fatty liver disease. There is a close connection and crosstalk between mitochondria and ER. The potential positive influence of mitigating ER stress (ERS) and mitochondrial damage in the context of preventing and treating fatty liver was explored in spotted seabass (Lateolabrax maculatus) as a susceptible model to fatty liver. A normal-fat diet (11% fat, NFD) and a high-fat diet (17% fat, HFD) were formulated and three additional diets were prepared by supplementation of quercetin (QUE) (0.1%), hydroxytyrosol (HT) (0.02%) or their combination (0.1% QUE + 0.02% HT) to the HFD (HFD + QUE HFD + HT and HFD + QUE + HT diets).Three replicate groups of fish (25 ± 0.02 g) were fed the test diets to visual satiety for 8 weeks. The results revealed the deterioration of growth, feed intake and feed utilization in HFD group compared to the NFD group whereas QUE and HT application improved their values and the optimum results were achieved for the HFD + QUE + HT group. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and both serum and hepatic triglyceride (TG), total cholesterol (T-CHO) and non-esterified free fatty acids (NEFA) concentrations were enhanced in HFD group, and their values decreased by QUE and HT, particularly their combined supplementation. The results of oil red O staining exhibited a remarkable reduction in number of lipid droplets in the liver of fish from HFD + QUE + HT group compared to the HFD group. Whole-body and muscle fat contents and abdominal fat index decreased by QUE and HT application. Expression of lipid metabolism related genes (srebp-1c, fas, acc) were down-regulated by QUE and HT treatment. Co-supplementation of QUE and HT down-regulated the expression of ERS-related genes (grp78, chop, perk, atf6, ire1), improved ER ultrastructure, and enhanced the coupling between mitochondria and ER. Moreover, expression of genes associated with hepatic mitochondrial biogenesis (pgc1-α, pgc1-β, nrf1) and mitophagy (pink1, atg5, mul1) was up-regulated in HFD + QUE, HFD + HT and HFD + QUE + HT groups. These data suggest that combined supplementation of QUE and HT in HFD for spotted seabass can improve growth and feed utilization, reduce hepatic damage and fat accumulation, and alleviate HFD induced ERS and mitochondrial dysfunction.

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition.

Hydroxytyrosol (HT), a phenolic extra-virgin olive oil compound used as a food supplement, has been recognized to protect liver function and alleviate stress-induced depressive-like behaviors. However, its protective effects against stress-induced liver injury (SLI) remain unknown. Here, the anti-SLI effect of HT was evaluated in mice with chronic unpredictable mild stress-induced SLI. Network pharmacology combined with molecular docking was used to clarify the underlying mechanism of action of HT against SLI, followed by experimental verification. The results showed that accompanying with the alleviation of HT on stress-induced depressive-like behaviors, HT was confirmed to exert the protective effects against SLI, as represented by reduced serum corticosterone (CORT), aspartate aminotransferase and alanine aminotransferase activities, as well as repair of liver structure, inhibition of oxidative homeostasis collapse, and inflammation reaction in the liver. Furthermore, core genes including histone deacetylase 1 and 2 (HDAC1/2), were identified as potential targets of HT in SLI based on bioinformatic screening and simulation. Consistently, HT significantly inhibited HDAC1/2 expression to maintain mitochondrial dysfunction in an autophagy-dependent manner, which was confirmed in a CORT-induced AML-12 cell injury and SLI mice models combined with small molecule inhibitors. We provide the first evidence that HT inhibits HDAC1/2 to induce autophagy in hepatocytes for maintaining mitochondrial dysfunction, thus preventing inflammation and oxidative stress for exerting an anti-SLI effect. This constitutes a novel therapeutic modality to synchronously prevent stress-induced depression-like behaviors and liver injury, supporting the advantaged therapeutic potential of HT.

New insight into PAH4 induced hepatotoxicity and the dose-response assessment in rats model

PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 μg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 μg/kg·bw and 0.11 μmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.

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

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

Accidental monensin poisoning in goats

Sodium monensin is the most frequently used ionophore as a growth promoter in ruminant diets. It has numerous benefits; however its toxic effects have also been observed in several animal species. Naturally occurring cases have not yet been reported in goats. This study describes an outbreak of accidental poisoning, characterizing its clinical, laboratory and pathological findings. Thirty-seven of 40 Anglo Nubian goat kids became intoxicated after receiving a diet that was erroneously supplemented with sodium monensin. They ingested an estimated toxic dose between 25 and 39 mg/kg BW. Clinical evolution was monitored (n = 27), followed by serum creatine kinase (CK) and aspartate aminotransferase (AST) activities measurements, and blood gas analysis. Postmortem examinations were performed between 1 and 8 days of evolution (n = 14). Clinical signs began 5 h after ingestion and included reticuloruminal hypomotility, lethargy, anorexia, tachycardia, cardiac arrhythmia, wet cough, pulmonary and tracheal crackles, and serous nasal discharge. The morbidity and lethality rates were 92.5 and 62.1%, respectively. CK and AST activities increased, reaching median values of 10,860 and 1596 U/L, respectively; the hyperchloremic metabolic acidosis was mild. The lesions were characterized by degeneration and necrosis of the cardiac and skeletal muscles, pulmonary congestion and edema, and passive liver congestion. The kids essentially developed cardiomyopathy with left and right congestive heart failures. Unlike in other ruminant species, skeletal muscle functional disability was infrequent. It can be concluded that monensin is toxic to goats and should be used with caution in their diet.

Effects of Dietary Curcumin on Growth and Flesh Quality in Juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus)

This experiment was designed to investigate the effects of curcumin levels on growth, flesh quality, and oxidative resistance in juvenile genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Fish (initial mean weight: 4.5 ± 0.3 g) were randomly fed five diets with curcumin supplementation levels of 0 (control), 150, 300, 600, and 1,200 mg/kg. After 60 days of feeding, the hepatosomatic index was significantly reduced in the curcumin supplemented groups. The 300 mg/kg group had the highest crude protein content of the whole fish. Compared to the control group, the crude fat content of whole fish in the 150 and 300 mg/kg groups was significantly reduced by 18.83%–19.74%, respectively. The highest values for muscular hardness, chewiness, myofibrillar density, and proportion of small-sized myofibers (&lt;40 μm) were observed in the 300 mg/kg group. The levels of total nonessential amino acids and bitter amino acids in muscle were significantly lower in the 150 and 300 mg/kg groups than in the other groups. The 300 mg/kg group had higher levels of free sweet amino acids in the muscle than the other groups. Muscles from the 150, 300, and 600 mg/kg groups had significantly higher levels of umami amino acids than in the other groups. The levels of total free nonessential amino acids and total amino acids in serum were significantly higher in the 300 mg/kg group than in the control group. Serum aspartate transaminase activity was significantly lower in the curcumin supplementation groups than in the control group, and the serum alanine aminotransferase activity was significantly lower in the 150 mg/kg group than in the other groups. Serum superoxide dismutase activity was significantly higher in the curcumin supplementation groups than in the control group. Serum catalase activity was significantly higher in the 150 mg/kg group than in the other groups. The serum malondialdehyde level was lowest in the 150 mg/kg group. These results suggest that dietary curcumin supplementation in the diet at 150–300 mg/kg can effectively improve the nutritional value, muscle flavor, and antioxidant capacity of tilapia.

Gentiopicroside ameliorates CCl4-induced liver injury in mice by regulating the PPAR-γ/Nrf2 and NF-κB/IκB signaling pathways.

This study explored the mechanisms by which gentiopicroside protects against carbon tetrachloride (CCl4)-induced liver injury. Male mice were randomly assigned to the control; CCl4; bifendate 100 mg/kg; or gentiopicroside 25, 50, or 100 mg/kg groups. Both vehicle and drugs were administered intragastrically for 7 days. Mice were administered CCl4 intraperitoneally 1 hour after the last drug dose. After 24 hours, we collected blood and liver samples for testing. Gentiopicroside significantly reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities with corresponding reductions in hepatocyte denaturation and necrosis. Gentiopicroside enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and glutathione levels and reduced heme oxygenase 1 (HO-1) activity and malondialdehyde levels in the liver, and these effects were attributed to peroxisome proliferator-activated receptor (PPAR)-γ/nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Meanwhile, gentiopicroside significantly downregulated HO-1 and upregulated SOD and GSH-Px at the mRNA level in the liver. Furthermore, gentiopicroside significantly suppressed serum tumor necrosis factor-α and interleukin-1β secretion, which was associated with the inhibition of nuclear factor-kappa B (NF-κB)/inhibitor of NF-κB (IκB). Gentiopicroside ameliorated CCl4-induced liver injury in mice via the PPAR-γ/Nrf2 and NF-κB/IκB pathways.

Dietary zinc levels affect growth, appetite, and lipid metabolism of Chinese perch (Siniperca chuatsi).

An 84-day feeding experiment was conducted to investigate the effects of dietary Zn (zinc) on growth performance, food intake, and lipid metabolism of Chinese perch (Siniperca chuatsi). Five isonitrogenous and isolipidic diets with differential Zn contents (67, 100, 149, 230, and 410mg/kg) were fed to 270 fish (35.47 ± 0.49g). Results showed that fish growth and food intake increased markedly with the dietary 149mg/kg Zn levels. Meanwhile, the food intake of 149mg/kg group was significantly higher than that of other treatment groups after feeding for 8weeks (P < 0.05). The qRT-PCR results showed that the expression of center appetite regulation factors in the hypothalamus was significantly regulated, and 149mg/kg significantly increased mRNA expression of npy (neuropeptide Y) and decreased pomc (anorexigenic proopiomelanocortin) and cart (cocaine- and amphetamine-regulated transcript) gene expression. Meanwhile, the expressions of the main genes (such as leptin A and ghrelin) involved in peripheral appetite regulation factors were significantly up-regulated firstly and then reduced with the dietary Zn level increased, whereas the expression of cck (cholecystokinin) was significantly up-regulated. Serum AST (aspartate transaminase) and ALT (alanine transaminase) activities in fish fed the diets containing 230 and 410mg/kg were significantly higher than that in other groups (P < 0.05). The lipid content of liver in 67 and 100mg/kg groups was significantly higher than other groups (P < 0.05). Furthermore, dietary Zn significantly elevated the serum TG (triglyceride) and TCHO (total cholesterol) content levels (P < 0.05). Fish fed a high Zn diet (149, 230, and 410mg/kg) dramatically down-regulated expression of srebp1 (sterol regulatory element binding proteins1c) and fas (fatty acid synthetase), but up-regulated expression of pparα (peroxisome proliferators-activated receptor-α) and cpt1 (carnitine palmitoyl transferase I) in the liver. The optimal dietary Zn inclusion level ranged from 146.69 to 152.86mg/kg diet, based on two-slope broken-line regression analysis of WGR (weight gain rate) and FCR (feed conversion rate) for Chinese perch.

Impact of dietary piperine on growth performance, immune response, antioxidant status, and immune-related gene expression in pathogen-aggravated Cyprinus carpio

This study investigated the effects of dietary piperine (PIP) on growth performance, digestive enzymes, serum biochemical parameters, antioxidant and immune responses, and gene expression in Cyprinus carpio challenged with Aeromonas hydrophila. Six diets were prepared with PIP doses of 0, 0.5, 1.0, 2.0, 3.0, and 4.0 g/kg, corresponding with the control, PR50, PR100, PR200, PR300, and PR400, respectively. Fish were challenged with Aeromonas hydrophila after 8 weeks of feeding with the respective diets. Weight gain (PWG) and specific growth rate (SGR) were significantly enhanced, whereas feed conversion ratio (FCR) was lowered in PR200. The cumulative post-challenge survival was improved to 68.43% in the PR200 group compared with 28.08% in the control. Serum total protein and albumin levels were significantly enhanced in the PR200 group compared to the control. However, dietary PIP up to 3 g/kg had no significant effect on serum glucose, cortisol, aspartate aminotransferase, or alkaline phosphatase activities; however, the alanine aminotransferase level was lower (P < 0.05) in the PR200 group than in the control. Intestinal amylase, lipase, and protease activities increased in PR300, and intestinal amylase and lipase increased in the PR100 group (P < 0.05). The serum immunological indices (lysozyme, alternative complement pathway, phagocytic activity, and respiratory burst activity) were higher (P < 0.05) in the PR200 group than in the control group. Serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities were significantly intensified in PR200–PR300 than in the control group, with the highest activity observed in the PR200 group. Malondialdehyde was significantly lower in the PR200 group than in the control group. Furthermore, SOD, CAT, and Nrf2 expression was strongly upregulated in the liver tissue of the PR200 and PR300 groups compared to that in the control. The transcript levels of pro-inflammatory cytokines viz. IL-1β and TNF-α were significantly upregulated in the kidneys of the PR100 and PR200 post-challenged. In contrast, the anti-inflammatory cytokine IL-10 was significantly downregulated in the kidneys of PR200. The expression of HSP70 was upregulated only in the PR400. Quadratic regression analysis showed that the optimal dietary PIP level was estimated as 2.07−2.13 g/kg to maximize growth performance. Overall, these results indicate that dietary PIP at an appropriate level can improve immunity, cytokine gene expression, and disease resistance in C. carpio.

Effects of Formulated Diet and Frozen Fresh Fish on Growth, Serum Biochemical Indexes, Liver Antioxidant, and Lipid Metabolism of Juvenile Cobia (Rachycentron canadum)

Feed is the main source of material and energy for farmed fish, and its nutritional value and balance are important factors affecting fish’s growth rate and physical health. In order to explore the effects of two different feed sources on the growth, serum biochemical indexes, liver antioxidant capacity, and lipid metabolism of young cobia fish, 300 young cobia fish with an initial body weight of 43.14 ± 1.25 g were selected for the experiment and randomly divided into two treatments. Each treatment had five replicates, and each replicate had 30 fish. They were fed with formulated feed and frozen fresh fish, respectively, for 12 weeks. The results showed that the weight gain rate, specific growth rate, and feed conversion rate of juvenile cobia fish fed with formulated diet were extremely significantly lower than those of the frozen fresh fish group ( P &lt; 0.01 ), and condition factor was significantly lower than that of the frozen fresh fish group ( P &lt; 0.05 ). However, protein efficiency rate, hepatosomatic index, and viscerosomatic index were significantly higher than those of frozen fresh fish group ( P &lt; 0.05 ). The content of water, crude protein, and crude ash in the whole fish had no significant difference ( P &gt; 0.05 ), while the content of crude lipid decreased significantly ( P &lt; 0.05 ). The serum aspartate aminotransferase activity and sugar content of cobia in the formulated diet group were significantly higher than those in the frozen fresh fish group ( P &lt; 0.05 ). In contrast, the total cholesterol, triglyceride content, alkaline phosphatase activity, and phosphorus content were significantly lower than those in the frozen fresh fish group ( P &lt; 0.05 ). Compared with the frozen fresh fish group, the antioxidant enzyme activities in the liver of the formulated diet group were significantly decreased ( P &lt; 0.05 ) except malondialdehyde (MDA) and the activity of fatty acid synthase, while there was no significant difference in the malate dehydrogenase. The study showed that under the experimental conditions, frozen fresh fish was more suitable for feeding juvenile cobia, and the formulated diet had adverse effects on the liver of juvenile cobia. Therefore, the nutritional composition of frozen fresh fish and the metabolic characteristics of cobia were used for reference to optimize and adjust the nutritional formula of juvenile cobia.

Double-edged effect of sodium citrate in Nile tilapia (Oreochromis niloticus): Promoting lipid and protein deposition vs. causing hyperglycemia and insulin resistance.

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating glucose and lipid metabolic homeostasis. However, the action of citrate in regulating nutrient metabolism in fish remains poorly understood. Here, we investigated the effects of dietary sodium citrate on growth performance and systematic energy metabolism in juvenile Nile tilapia (Oreochromis niloticus). A total of 270 Nile tilapia (2.81±0.01g) were randomly divided into three groups (3 replicates per group, 30 fish per replicate) and fed with control diet (35% protein and 6% lipid), 2% and 4% sodium citrate diets, respectively, for 8 weeks. The results showed that sodium citrate exhibited no effect on growth performance (P>0.05). The whole-body crude protein, serum triglyceride and hepatic glycogen contents were significantly increased in the 4% sodium citrate group (P < 0.05), but not in the 2% sodium citrate group (P>0.05). The 4% sodium citrate treatment significantly increased the serum glucose and insulin levels at the end of feeding trial and also in the glucose tolerance test (P < 0.05). The 4% sodium citrate significantly enhanced the hepatic phosphofructokinase activity and inhibited the expression of pyruvate dehydrogenase kinase isozyme 2 and phosphor-pyruvate dehydrogenase E1 component subunit alpha proteins (P < 0.05). Additionally, the 4% sodium citrate significantly increased hepatic triglyceride and acetyl-CoA levels, while the expressions of carnitine palmitoyl transferase 1a protein were significantly down-regulated by the 4% sodium citrate (P < 0.05). Besides, the 4% sodium citrate induced crude protein deposition in muscle by activating mTOR signaling and inhibiting AMPK signaling (P < 0.05). Furthermore, the 4% sodium citrate significantly suppressed serum aspartate aminotransferase and alanine aminotransferase activities, along with the lowered expression of pro-inflammatory genes, such as nfκb, tnfα and il8 (P < 0.05). Although the 4% sodium citrate significantly increased phosphor-nuclear factor-kB p65 protein expression (P < 0.05), no significant tissue damage or inflammation occurred. Taken together, dietary supplementation of sodium citrate could exhibit a double-edged effect in Nile tilapia, with the positive aspect in promoting nutrient deposition and the negative aspect in causing hyperglycemia and insulin resistance.

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.