Plasma Aspartate Aminotransferase Research Articles

Akkermansia muciniphila MucT attenuates sodium valproate-induced hepatotoxicity and upregulation of Akkermansia muciniphila in rats.

In the previous study, we found that the oral sodium valproate (SVP) increased the relative abundance of Akkermansia muciniphila (A. muciniphila) in rats, and plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) activities were positively correlated with A. muciniphila levels. This study aimed to further investigate the role of A. muciniphila in SVP-induced hepatotoxicity by orally supplementing rats with the representative strain of A. muciniphila, A. muciniphila MucT. Additionally, the fresh faeces were incubated anaerobically with SVP to investigate the effect of SVP on faecal A. muciniphila in the absence of host influence. Results showed that A. muciniphila MucT ameliorated the hepatotoxicity and upregulation of A. muciniphila induced by SVP. SVP also induced a noteworthy elevation of A. muciniphila level invitro, supporting the observation invivo. Therefore, we speculate that A. muciniphila MucT may be a potential therapeutic strategy for SVP-induced hepatotoxicity. In addition, the increased A. muciniphila induced by SVP may differ from A. muciniphila MucT, but further evidence is needed. These findings provide new insights into the relationships between A. muciniphila and SVP-induced hepatotoxicity, highlighting the potential for different A. muciniphila strains to have distinct or even opposing effects on SVP-induced hepatotoxicity.

Determination of Weight and Biochemical Changes in Layers Experimentally Infected with Escherichia coli

This study determined the effect of experimental exposure of layer chickens to Escherichia coli (E. coli) on weight, egg production and some plasma biochemical parameters. A total of 20 laying chickens (20 weeks old) were acquired and assigned, at random, into infected and control groups, of 10 layers each. Birds in the infected group were challenged with 0.5 ml of bacterial aliquot containing 109 colony forming units (CFU) of the bacteria, administered intra tracheally. Five birds, from each group were selected at random and their live body weights were determined on days 0, 2, 4, 6, 14, 21, 28, 35 and 42. Also, egg production was monitored, and the weekly percentage egg production of birds was calculated. Two (2) ml of blood were collected from each bird in both groups and used for plasma biochemical analyses. Finding from the research showed that E. coli infection caused reduction in feed and water consumption by day 3 post infection (pi); with subsequent reduction in body weight and egg production. The mean plasma aspartate aminotransferase (AST) activity in the infected group progressively increased from day 6 pi to reach a significantly higher (p < 0.05) value (66.4 ± 0.93 IU/L) on day 28 pi while the mean plasma alanine aminotransferase (ALT) activity progressively increased in the infected group from day 6 pi to attain the highest significant (p < 0.05) value (74.4 ± 2.11 IU/L) on day 21 pi. The mean plasma total protein concentration in the infected group decreased from day 4 pi and reached the lowest significant (p < 0.05) value (5.12 ± 0.28 mg/dl) on day 35 pi. In conclusion, the drop in egg production, loss of body weight, increase hepatic transaminases and decrease plasma protein may be attributed to anorexia or possible impairment of intestinal, renal reabsorption of nutrients from the infection.

Apigenin ameliorates diabetic neuropathy in rats by modulating the TLR4/MyD88 signaling pathway

Objective: To determine the neuroprotective effects of apigenin against streptozotocin (STZ)-induced diabetic neuropathy (DN). Methods: To induce DN, Wistar rats (150-200 g) were administered with STZ (55 mg/kg, i.p.). Then they were randomly assigned to various groups, viz., normal, diabetic control, insulin (10 IU/kg, s.c.), apigenin (5, 10, and 20 mg/kg, p.o.), and insulin (10 IU/kg) plus apigenin (20 mg/kg, p.o.). Various behavioral, biochemical, and molecular markers [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor erythroid 2-related factor 2 (Nrf2)] were assessed. Results: Apigenin (10 and 20 mg/kg, p.o.) substantially reduced plasma glucose levels, lipid profile, aspartate transaminase, alanine transaminase, glycated hemoglobin, and neural advanced glycation end products in STZ-induced DN rats (P<0.05). After apigenin intervention, STZ-induced changes in food and water intake, body weight, urine output, allodynia, hyperalgesia, and insulin levels were markedly improved (P<0.05). Neural antioxidant enzymes (superoxide dismutase and glutathione) and Na+K+ATPase activity were also considerably elevated (P<0.05) while the level of lipid peroxidation was diminished following apigenin therapy (P<0.05). Furthermore, apigenin markedly upregulated the Nrf2 mRNA level while downregulating the mRNA expressions of TNF-α and ILs and the protein expressions of TLR4 and MyD88 (P<0.05). STZ-induced histological abnormalities in the sciatic nerve were also improved by apigenin treatment. Conclusions: Apigenin exerts its neuroprotective effect by modulating the inflammatory and oxidative stress pathways via regulating the TLR4-MyD88 signaling pathway.

Changes in liver metabolic pathways demonstrate efficacy of the combined dietary and microbial therapeutic intervention in MASLD mouse model

ObjectiveMetabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. MethodsMASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis. ResultsAfter the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver. ConclusionsThese data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD.

Black soldier fly pulp in the diet of golden pompano: Effect on growth performance, liver antioxidant and intestinal health

Black soldier fly (Hermetia illucens) has been widely researched as a protein source for fish meal replacement in aquaculture, but few studies have focused on its potential as a feed additive for growth and immune enhancement. We conducted a 56-day culture experiment to determine the impact of feed addition of black soldier fly pulp (BSFP, with 86.2% small peptides in dry basis) on growth performance, plasma biochemistry, liver antioxidant levels, intestinal immunity, digestion and microbiota of juvenile golden pompano (Trachinotus ovatus, 5.63 ± 0.02 g). BSFP was added to the basal diet at 0%, 1%, 3%, 5%, 7% and 9% (named Control, BSFP-1, BSFP-3, BSFP-5, BSFP-7, BSFP-9), respectively. BSFP increased the weight gain rate, specific growth rate, protein efficiency ratio and reduced the feed conversion rate of juvenile T. ovatus, the optimal growth performance was reached at BSFP-1, after which a negative feedback phenomenon was observed. Low levels of BSFP upregulated the expression of hepatic antioxidant, intestinal tight junctions, anti-inflammatory related genes and enhanced antioxidant, immune and intestinal digestive enzyme activities, which simultaneously reduced hepatic malondialdehyde and plasma aspartate transaminase and alanine aminotransferase concentrations. However, at BSFP-7, catalase activity was significantly reduced, while NF-κB p65 and pro-inflammatory cytokines transcription was significantly enhanced (P < 0.05). The results suggest that high doses of BSFP addition may damage fish health by inhibiting small peptide uptake, decreasing the activity of antioxidant enzyme and activating the canonical NF-κB pathway. Conversely, low doses of BSFP enhanced intestinal tight junction protein transcription, digestive enzyme activity and immune performance, inhibited pathogenic microbiota, while enhancing liver antioxidant capacity, which was associated with activated Nrf2-Keap1 pathway and suppressed NF-κB pathway, showing its potential as a feed additive to aquafeeds.

Evaluation of black soldier fly larvae meal as a functional feed ingredient in Atlantic salmon (Salmo salar) under farm-like conditions

Atlantic salmon (Salmo salar) were fed diets containing black soldier fly larvae (BSFL) meal at two inclusion levels for 13 months in open sea-cages. BSFL meal replaced plant-based ingredients and dietary insect meal inclusion levels were at 5% and 10%. A commercial salmon diet was fed as a control diet. Fish were reared from ~173 g to ~ 4 kg and were randomly distributed into nine open sea-cages with ~6000 salmon/cage (12×12 m2; 1900 m3). Fish from the sea-cages were sampled at two time points (mid and final samplings) to study the dietary effects of BSFL meal on the general health and welfare. Monthly assessments of sea-lice and gill score were conducted to evaluate the overall well-being of the salmon. The findings from the current study revealed that dietary inclusion of BSFL meal up to 10% did not have any significant effects in general growth, welfare or survival. However, significant positive response was observed in the general skin mucosal, hematological, and gene expression profiles of salmon. Notably, the group of salmon fed with 5% BSFL meal showed a significant decrease in plasma aspartate transaminase and alanine transaminase. Also, a significantly higher expression of interleukin1β in both skin and gill along with upregulation of matrix metallopeptidase9 and mucin18 in gill were observed in salmon fed BSFL at 5%, which aided in increased immune responses. Apart from that, this group had significantly higher mucus secretions, decreased cortisol response and increased number of erythrocytes. Furthermore, the delousing stress had a significant effect on the plasma cortisol, and these responses were independent of the dietary effect. Moreover, these immune responses behaved differently at different fish size and time points, acknowledging the influence of various factors in immune modulation. Overall, the findings from this study showed the effects of dietary BSFL meal to modulate the immune status of salmon. This study aims to fill the existing knowledge gaps regarding the impact of incorporating BSFL meal as a functional feed ingredient into the salmon diet on health and immune status replicating real farm conditions.

Baseline and recurrent exposure to the standard dose of artemisinin-based combination therapies (ACTs) induces oxidative stress and liver damage in mice (BALB/c)

BackgroundIn malaria-endemic countries, repeated intake of artemisinin-based combination therapies (ACTs) is rampant and driven by drug resistance, improper usage, and easy accessibility. Stress effects and potential liver toxicity due to the frequent therapeutic use of ACTs have not been extensively studied. Here, we investigated the effects of repeated treatment with standard doses of the commonly used ACTs artemether/lumefantrine (A/L) and artesunate-amodiaquine (A/A) on oxidative stress and liver function markers in male mice (BALB/c).MethodsForty Five mice were divided into three groups: control, A/L, and A/A. The drugs were administered three days in a row per week, and the regimen was repeated every two weeks for a total of six cycles. The levels of oxidative stress and liver function markers were measured in both plasma and liver tissue after initial (baseline) and repeated exposures for the second, third, and sixth cycles.ResultsExposure to A/L or A/A caused a significant (p < 0.001) increase in plasma malondialdehyde (MDA) levels after the first and repeated exposure periods. However, Hepatic MDA levels increased significantly (p < 0.01) only after the sixth exposure to A/A. Following either single or repeated exposure to A/L or A/A, plasma and liver glutathione peroxidase (GPx) and catalase (CAT) activities, plasma aspartate and alanine transaminase, alkaline phosphatase activity, and bilirubin levels increased, whereas total plasma protein levels decreased significantly (p < 0.001). Varying degrees of hepatocyte degeneration and blood vessel congestion were observed in liver tissues after a single or repeated treatment period.ConclusionIrrespective of single or repeated exposure to therapeutic doses of A/L or A/A, plasma oxidative stress and liver damage were observed. However, long-term repeated A/A exposure can led to hepatic stress. Compensatory processes involving GPx and CAT activities may help reduce the observed stress.

Tubuloside A, a phenylethanoid glycoside, alleviates diclofenac induced hepato-nephro oxidative injury via Nrf2/HO-1.

The most prominent adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DF) are hepato-renal damage. Natural antioxidants can be preferred as an alternative and/or combination to improve this damage. This present study was conducted to evaluate the protective effect of Tubuloside A (TA) against diclofenac (DF)-induced hepato-renal damage. TA (1 mg/kg, ip) was administered to male Sprague-Dawley rats for 5 days, and DF (50 mg/kg, ip) was administered on Days 4 and 5. Plasma aspartate amino transferase, alanine amino transferase, alkaline phosphatase, blood urea nitrogen and creatinine were measured to evaluate liver and kidney functions. Additionally, oxidative stress parameters (malondialdehyde, glutathione, superoxide dismutase, catalase, and 8-oxo-7,8-dihydro-2'-deoxyguanosine) in blood, liver, and kidney tissues, changes in mRNA expression of genes involved in the Nrf2/HO-1 signalling pathway (Nrf2, HO-1, NQO-1, IL-6, iNOS, Cox-2, TNF-α, IL1-β and NFκB) and apoptotic process (Bcl-2, Cas-3 and Bax) in liver and kidney tissues were determined. Additionally, tissue sections were evaluated histopathologically. Biochemical, histopathological, and molecular results demonstrated the hepato-renal toxic effects of DF, and TA treatment protected the liver and kidney from DF-induced damage. This provides an explanation for the hepato-nephro damage caused by DF and offers new ideas and drug targets together with TA for the prevention and treatment of DF injury.

Safety, tolerability and biological responses of Oreochromis niloticus juveniles upon oral oxolinic acid administration.

In aquaculture, oxolinic acid (OA) is used as a second-line treatment at 12 mg/kg biomass/day for seven consecutive days. The present study evaluated the biosafety of 21 days of dietary administration of OA at 0, 12, 36, 60 and 120 mg by assessing the growth, biochemical, erythrocytic morphological and histopathological alterations and residue levels in Oreochromis niloticus. A significant dose-dependent reduction in feed intake and biomass and an increase in mortalities and erythrocytic cellular and nuclear changes were recorded. Significant elevations in plasma glucose, creatinine, alkaline phosphatase, alanine transaminase and aspartate transaminase and a decline in calcium and chloride levels were documented. The kidney, liver and intestine histoarchitecture showed mild to marked alterations. The edible tissue OA residues peaked on day 21 and decreased upon cessation of administration in all the dosing groups. The residue levels in the muscle of the recommended dose group were well within the maximum residue limit set by the European Medicines Evaluation Agency. Although the current study hinted at the safety and tolerability of OA even during long-term usage in O. niloticus in Indian conditions, care must be exercised for its aquacultural application because of its listing as a critically important medicine for humans.

Promotion of growth and resistance against Aeromonas hydrophila in Nile tilapia juveniles supplemented with Citrus limon extract

This study aimed to investigate the effects of dietary supplementation with Citrus limon (L.) extract (CLE) on the growth, hematological, and biochemical parameters of Nile tilapia juveniles (Oreochromis niloticus L.). The chemical composition of CLE was detected using nuclear magnetic resonance and mass spectrometry. Three hundred and sixty fish (12.80 ± 0.13 g) were distributed in a completely randomized experimental design with six treatments and four replicates (15 fish per tank). Six diets with different levels of CLE in the diet – 0.0 (control), 0.2, 0.4, 0.8, 1.6, and 3.2 g kg−1 – were evaluated for 60 days, followed by 8 days of Aeromonas hydrophila challenge. The bacterial inoculum was diluted in sterile saline at 1 × 107 colony-forming units mL−1. The major constituents of CLE were phenolic compounds (mainly flavonoids) and polysaccharides. Quadratic regression showed that fish supplemented with 1.6 g CLE kg diet−1 improved final weight, weight gain, feed intake, feed conversion ratio, and perivisceral fat index. Before bacterial infection, fish supplemented with 1.6 g CLE kg diet−1 showed a higher hepatosomatic index and erythrocytes (according to linear regression) and higher plasma total protein and hemoglobin (according to quadratic regression). After bacterial infection, quadratic regression showed that 0.8–3.2 g CLE kg diet−1 reduced the plasma aspartate aminotransferase levels and mortality of juveniles. In conclusion, adding 1.6 g CLE kg diet−1 is recommended to improve Nile tilapia juveniles' growth performance, health, and survival after A. hydrophila infection.

Oral bovine serum albumin administration benefits plasma amino acid profile in blunt snout bream fed high‐fat and high‐energy diet through the TOR signaling pathway

AbstractThis study investigated the effect of oral bovine serum albumin (BSA) on plasma amino acid profile and growth performance in blunt snout bream fed high‐fat and high‐energy diets. A total of 360 fish (average weight: 45.84 ± 0.07 g) were randomly divided into three groups in four replicates and fed with the control, high‐fat diet (HFD), and high‐energy diet (HED), respectively. After 12 weeks of feeding, fish were orally administered with 10% BSA for 10 h, with the blood and liver sample obtained at 10 h. The results showed no remarkable difference (p &gt; 0.05) in final weight, weight gain rate, feed conversion ratio, protein efficiency ratio, and daily growth rate among dietary treatments. However, fish fed HFD and HED obtained significantly higher energy and nitrogen retention content than the control. Plasma valine and histidine content were more prevalent in fish fed the control diet than in HFD and HED groups. However, BSA significantly enhanced this content with higher values observed in arginine and alanine content than in control diets at 10 h. Significantly higher liver and plasma Aspartate aminotransferase, Xanthine oxidase, and Glutamate dehydrogenase content were found in the HFD than in the control group. However, the administration of BSA at 10 h improved these parameters similar to the control. Meanwhile, protease, Lipase, aminopeptidase N, carboxypeptidase A, and Na+ K+‐ATPase were influenced significantly (p &lt; 0.001) by sampling time, dietary treatments, and their interaction. Fish fed with the HFD and HED significantly downregulated (p &lt; 0.05) the akt, bcat2, 4e‐bp1, s6k1, and tor expression compared to the control. However, BSA administration at 10 h improved these genes similar to the control. This study indicated that oral BSA administration could benefit plasma amino acid through the TOR signaling pathway in blunt snout bream fed high‐fat and high‐energy diets.

Metabolic characteristics of voriconazole – Induced liver injury in rats

Voriconazole (VOR) – induced liver injury is a common adverse reaction, and can lead to serious clinical outcomes. It is of great significance to describe the metabolic characteristics of VOR – induced liver injury and to elucidate the potential mechanisms. This study investigated the changes of plasma metabolic profiles in a rat model of VOR – induced liver injury by non – targeted metabolomics. Correlation analysis was performed between differentially expressed metabolites and plasma liver function indexes. The metabolites with strong correlation were determined for their predictive performance for liver injury using receiver operating characteristic (ROC) curve analysis. Potential biomarkers were then screened combined with liver pathological scores. Finally, the expression level of genes that involved in lipid metabolism were determined in rat liver to verify the mechanism of VOR – induced liver injury we proposed. VOR – induced liver injury in rats was characterized by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, the lipid droplets accumulation in liver, as well as inflammation and fibrosis. Significant changes of plasma metabolites were observed, with a decrease in lipid metabolites accounting for over 50% of all changed metabolites, and alterations of cholesterol and bile acids metabolites. The decrease of 3 phosphatidylcholine (PC) in plasma could indicate the occurrence of VOR – induced liver injury. Decreased fatty acids (FA) oxidation and bile acid excretion might be the potential mechanisms of VOR – induced liver injury. This study provided new insights into the molecular characterization of VOR – induced liver injury.

Protective effect of liriodendrin against liver ischaemia/reperfusion injury in mice via modulating oxidative stress, inflammation and nuclear factor kappa B/toll-like receptor 4 pathway.

The aim of the present study was to investigate the protective effect and mechanism of liriodendrin (LDN) is a lignan diglucoside in hepatic ischaemia/ /reperfusion (I/R) injury. The liver I/R was established in male C57BL/6 mice. The effect of LDN is initially investigated on hepatic I/R injury via estimating histopathology of liver. The level of metabolic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) was studied along with apoptosis of mouse hepatocytes via TUNEL and flow cytometry analysis. The effect of LDN was investigated on oxidative stress biomarkers (glutathione [GSH] content, malondialdehyde [MDA] and superoxide dismutase [SOD] activities) and pro-inflammatory cytokines (tumour necrosis factor alpha [TNF-α], interleukin [IL]-1β and IL-6). Western blot study was also conducted to elucidate the effect of LDN on toll-like receptor 4/nuclear factor kappa B (TLR4/NF-kB). Liriodendrin alleviates liver I/R injury, as manifested by decreased plasma ALT, AST and ALP with improvement in liver necrotic area. LDN also reduces apoptosis of mouse hepatocytes with reduction of oxidative stress and generation of pro-inflammatory cytokines. It significantly reduces the expression of TLR4 and NF-kB. The study demonstrated that LDN reduces liver injury and prevented apoptosis of hepatocytes following I/R injury. In addition, LDN also reduces oxidative stress, inflammation, and TLR4/NF-kB in I/R injured mice.

Effects of humic acid on nutrient removal efficiency of aquatic duckweed (Lemna minor) and both growth performance, and hemato-biochemical parameters of Nile tilapia (Oreochromis niloticus) cultured in water recirculating system

This study was carried out to evaluate the effects of humic acid (HA) on the nutrient removal efficiencies of aquatic duckweed plant (Lemna minor) from a water recirculating system used to culture Nile tilapia (Oreochromis niloticus) fish for 30 days. The HA was added to water at three concentrations of 0 (Control), 1.5, and 3 mg/L in triplicate. Water quality parameters, growth performance, and some hemato-biochemical parameters of the fish in variable HA concentrations were compared. The total ammonia nitrogen (TAN) and total phosphorous (TP) removal efficiency of L. minor increased with increasing the HA concentration from 0 mg/L to 3 mg/L (p < 0.05). The concentration of nitrate (NO3 −) in the HA-3 mg/L was higher than that in the other groups on days 20 and 30 of the fish cultivation period (p < 0.05). The growth performance of fish improved in the HA-3 mg/L compared to the other groups. The addition of different concentrations of HA to water had no adverse effect on the hematological properties of the Nile tilapia. The plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in the HA-0 mg/L and HA-1.5 mg/L groups were higher than in the HA-3 mg/L (p < 0.05). No significant differences in the plasma glucose and cholesterol levels were observed between the HA-groups (p > 0.05), while the triglyceride level increased in the HA-3 mg/L compared to the control (p < 0.05). These results indicated that adding HA to water could be an effective method to enhance the bioremediation performance of the aquatic duckweed plants as biofilter and thus improve water quality, subsequently, fish growth performance in RASs.

Hepatoprotective and in vivo antioxidant effects of granulometric classes and decoction of Ficus dicranostyla Mildbread leaves powders against carbon tetrachloride-induced hepatotoxicity in Wistar rats.

Ficus dicranostyla is a plant from the Moraceae family commonly used in African countries for its nutritional value and its believed medicinal properties. Its antioxidant in vitro capacity and its richness in phenolic compounds have been previously demonstrated. This work aimed at evaluating the hepatoprotective and in vivo antioxidant activities of different granulometric fractions of the F. dicranostyla leaves against carbon tetrachloride-induced hepatotoxicity in rats. Powdery fractions (<125, 250-125, and ≥250 μm), and the unsieved powder, obtained from the F. dicranostyla leaves were water-dissolved and given orally to rats at the same dose (250 mg/kg body weight) before administering carbon tetrachloride intraperitoneally (1 mL/Kg bw). The lipid status parameters (total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol), hepatic toxicity through aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in blood plasma, and antioxidant status by measuring the malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in liver homogenate were performed. The activities of all parameters registered a significant (p < .05) alteration in CCl4-treated rats, which were significantly recovered toward an almost normal level in coadministered with Ficus dicranostyla leaf powder samples in a particle size-dependent manner. Results suggest that the smaller particle size of the powder fraction, as well as the decoction powder of Ficus dicranostyla, may be used as hepatoprotective and antioxidant agents.

Sasa veitchii extract alleviates nonalcoholic steatohepatitis in methionine–choline deficient diet‐induced mice by regulating peroxisome proliferator‐activated receptor alpha

AbstractAimNonalcoholic steatohepatitis (NASH) is a pandemic liver disease. This study aimed to explore the protective effects of Sasa veitchii extract (SE) in a mouse model of methionine–choline‐deficient (MCD) diet‐induced NASH.MethodsEight‐week‐old male C57BL/6J mice were fed a normal diet or an MCD diet for 8 weeks (0–8 weeks). SE (0.1 mL) was administered orally once daily for the latter period (4 weeks; 5–8 weeks). Body weight was measured weekly. The mice were euthanized and plasma samples were collected. Livers were collected and weighed.ResultsThe MCD diet decreased the liver/body weight ratio, elevated plasma alanine aminotransferase and aspartate aminotransferase levels, and increased liver oxidative stress, fibrosis, and inflammation. These changes were alleviated by SE administration. We also found that the MCD‐induced increase in triglycerides and lipid droplets in the liver was attenuated by SE. Furthermore, MCD‐induced glutathione peroxidase‐4 and peroxisome proliferator‐activated receptor‐alpha downregulation was sustained by SE administration.ConclusionOur results showed that SE protected mice against MCD‐induced hepatic injury, including oxidative stress and inflammation, by modulating peroxisome proliferator‐activated receptor alpha activation.

Risk prediction model for distinguishing Gram-positive from Gram-negative bacteremia based on age and cytokine levels: A retrospective study.

Severe infection often results in bacteremia, which significantly increases mortality rate. Different therapeutic strategies are employed depending on whether the blood-borne infection is Gram-negative (G-) or Gram-positive (G+). However, there is no risk prediction model for assessing whether bacteremia patients are infected with G- or G+ pathogens. To establish a clinical prediction model to distinguish G- from G+ infection. A total of 130 patients with positive blood culture admitted to a single intensive care unit were recruited, and Th1 and Th2 cytokine concentrations, routine blood test results, procalcitonin and C-reactive protein concentrations, liver and kidney function test results and coagulation function were compared between G+ and G- groups. Least absolute shrinkage and selection operator (LASSO) regression analysis was employed to optimize the selection of predictive variables by running cyclic coordinate descent and K-fold cross-validation (K = 10). The predictive variables selected by LASSO regression analysis were then included in multivariate logistic regression analysis to establish a prediction model. A nomogram was also constructed based on the prediction model. Calibration chart, receiver operating characteristic curve and decision curve analysis were adopted for validating the prediction model. Age, plasma interleukin 6 (IL-6) concentration and plasma aspartate aminotransferase concentration were identified from 57 measured variables as potential factors distinguishing G+ from G- infection by LASSO regression analysis. Inclusion of these three variables in a multivariate logistic regression model identified age and IL-6 as significant predictors. In receiver operating characteristic curve analysis, age and IL-6 yielded an area under the curve of 0.761 and distinguished G+ from G- infection with specificity of 0.756 and sensitivity of 0.692. Serum IL-6 and IL-10 levels were upregulated by more than 10-fold from baseline in the G- bacteremia group but by less than ten-fold in the G+ bacteremia group. The calibration curve of the model and Hosmer-Lemeshow test indicated good model fit (P > 0.05). When the decision curve analysis curve indicated a risk threshold probability between 0% and 68%, a nomogram could be applied in clinical settings. A simple prediction model distinguishing G- from G+ bacteremia can be constructed based on reciprocal association with age and IL-6 level.

Biochemical Response and Histopathologic Alterations in Papyrocranus afer from Banegbe River, Delta State, Nigeria

Aim: This study investigated the effects of pollutants on the biochemical and histopathological components of Papyrocranus afer obtained from the Banegbe River at different locations (upstream, middle-stream, and downstream). The effect of the pollutant on the checked were, levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in blood samples of the fishes and the histopathologic alterations of the gills and liver of the fishes. &#x0D; Methodology: The gills and liver tissue of the fish were collected and processed using routine histologic techniques for fixing and embedding in paraffin and staining sections with hem eosin. All the indices of the enzyme tests were estimated with the aid of Randox Diagnostic Test Kits following the manufacturer’s methods. &#x0D; Results: Evaluation of the plasma enzymes showed significant increases (p&lt;0.05) in plasma ALT, AST, and ALP activity in all the sampled points of Banegbe River when compared to the control 1 (Orogodo river) with middle-stream having significant (p&lt;0.05) higher concentrations when compared to down-stream and up-stream. The main alterations observed in the liver of the fish at the Banegbe River were Kupffer cell hyperplasia and focal necrosis of the liver. While the gills showed alteration of the structure of the epithelium, hyperplasia of the epithelium of the primary lamella, epithelial lifting, vacuolization, alteration of the structure, and occurrence of aneurysms in the secondary lamella, all these alterations were as a result of pollutant in the river. Control 1 showed normal parenchymal cells of the liver and normal gill structure. &#x0D; Conclusion: The increase in enzyme activities suggests leakage of these enzymes from the liver cytosol into the bloodstream as a result of liver damage by contaminants. From our results, it can be concluded that the Banegbe River is polluted as a result of effluents channeled in the river by industries within the environs.

Mitochondria of lung venular capillaries mediate lung-liver cross talk in pneumonia.

Failure of the lung's endothelial barrier underlies lung injury, which causes the high mortality acute respiratory distress syndrome (ARDS). Multiple organ failure predisposes to the mortality, but mechanisms are poorly understood. Here, we show that mitochondrial uncoupling protein 2 (UCP2), a component of the mitochondrial inner membrane, plays a role in the barrier failure. Subsequent lung-liver cross talk mediated by neutrophil activation causes liver congestion. We intranasally instilled lipopolysaccharide (LPS). Then, we viewed the lung endothelium by real-time confocal imaging of the isolated, blood-perfused mouse lung. LPS caused alveolar-capillary transfer of reactive oxygen species and mitochondrial depolarization in lung venular capillaries. The mitochondrial depolarization was inhibited by transfection of alveolar Catalase and vascular knockdown of UCP2. LPS instillation caused lung injury as indicated by increases in bronchoalveolar lavage (BAL) protein content and extravascular lung water. LPS or Pseudomonas aeruginosa instillation also caused liver congestion, quantified by liver hemoglobin and plasma aspartate aminotransferase (AST) increases. Genetic inhibition of vascular UCP2 prevented both lung injury and liver congestion. Antibody-mediated neutrophil depletion blocked the liver responses, but not lung injury. Knockdown of lung vascular UCP2 mitigated P. aeruginosa-induced mortality. Together, these data suggest a mechanism in which bacterial pneumonia induces oxidative signaling to lung venular capillaries, known sites of inflammatory signaling in the lung microvasculature, depolarizing venular mitochondria. Successive activation of neutrophils induces liver congestion. We conclude that oxidant-induced UCP2 expression in lung venular capillaries causes a mechanistic sequence leading to liver congestion and mortality. Lung vascular UCP2 may present a therapeutic target in ARDS.NEW & NOTEWORTHY We report that mitochondrial injury in lung venular capillaries underlies barrier failure in pneumonia, and venular capillary uncoupling protein 2 (UCP2) causes neutrophil-mediated liver congestion. Using in situ imaging, we found that epithelial-endothelial transfer of H2O2 activates UCP2, depolarizing mitochondria in venular capillaries. The conceptual advance from our findings is that mitochondrial depolarization in lung capillaries mediates liver cross talk through circulating neutrophils. Pharmacologic blockade of UCP2 could be a therapeutic strategy for lung injury.

Dietary protein, lipid and insect meal on growth, plasma biochemistry and hepatic immune expression of lake whitefish (Coregonus clupeaformis)

Studies are lacking that investigate the dietary nutrient requirements of lake whitefish (Coregonus clupeaformis), a newly farmed fish species in Ontario, Canada. Dietary levels of protein and lipid must be optimized to ensure high growth performance for the commercial success of this species. Additionally, the inclusion of insect meal in the diet may improve growth and immune response. The objective of this study was to evaluate the effects of dietary protein:lipid ratios and insect meal as a feed additive on the growth performance and hepatic immune function of juvenile lake whitefish (301 ± 10 g). A 16-week (112 day) trial was performed with five diets including a commercial control diet (BCC), and four experimental diets with high or low levels of protein (54 and 48%, respectively) and lipid (18 and 12%, respectively). The high protein dietary groups contained 5% of full-fat black soldier fly larvae (Hermetia illucens). Fish weights, viscera, liver, and blood were collected for further analysis. Specific growth rate, thermal growth coefficient and weight gain were significantly higher in fish fed with the BCC and high protein high lipid (HPHL) diets. However, viscerosomatic index was found to be significantly higher in fish fed the BCC diet, thus HPHL is more optimal for non-visceral weight gain. Higher levels of plasma phosphorus, aspartate aminotransferase and potassium indicated poor growth and stress in fish fed low lipid diets. Relative expression of HSP70, involved in cellular repair, was significantly downregulated in fish fed high lipid diets, and no effects were found on the expression of innate immune and oxidative stress genes. Also, IL8 (CXCL8) and catalase were upregulated (non-significant) in fish fed the HPHL diet with the largest weight gain. No effects of insects were found on growth, plasma biochemistry or gene expression, which suggests 5% dietary inclusion was too low. Overall, we recommend a HPHL diet for the cultivation of lake whitefish based on improved growth performance, low viscera weight, improved plasma biochemistry and downregulation of cellular repair genes.