AST Activities Research Articles

Mulberry galacto-oligosaccharides ameliorates non-alcoholic fatty liver disease in mice induced by a high-fat diet

A type of oligosaccharide named mulberry galacto-oligosaccharides (MGO), was isolated from mulberry with a galactose-only, weighs 987 Da and displays diverse biological properties. The objective of this work was to investigate the protective effects of MGO in non-alcoholic fatty liver disease (NAFLD) mice. The results showed that MGO can reduce the body weight and liver weight of NAFLD mice, and reduce the levels of NEFA, TG, TC and LDL-C in serum and liver as well as the activities of AST and ALT. Increase HDL-C content, SOD, and GSH activity in serum and improve pathological damage. MGO regulates the AMPK lipid metabolism pathway, upregulates the expression of ATGL, downregulates the expression of SREBP-1, inhibits lipogenesis, and promotes lipolysis. MGO alleviates liver function damage in NAFLD mice, improves blood lipids, liver metabolism, and increases the body’s antioxidant capacity, suggesting MGO potential as a dietary supplement and functional food to combat HFD-induced NAFLD.

Effect of Particle Size on Physical Properties, Dissolution, In Vitro Antioxidant Activity, and In Vivo Hepatoprotective Properties of Tetrastigma hemsleyanum Diels et Gilg Powders

Objective: The aim of this study was to analyze the effects of different particle sizes of Tetrastigma hemsleyanum Diels et Gilg (TDG) powders on physical properties, dissolution, in vitro antioxidant activity, and in vivo hepatoprotective properties. Methods: The particle size of TDG coarse powders (TDG-CP), TDG fine powders (TDG-FP), and TDG micro powders (TDG-MP) were measured by a laser particle size analyzer. The physical properties were measured according to the latest version of the Chinese Pharmacopoeia (Committee Chinese Pharmacopoeia 2020). The content of the total flavonoids, total polysaccharides, kaempferol-3-O-rutinoside, and rutin of TDG powders were determined using the NaNO2-Al (NO3)3 colorimetric method, the sulphate-phenol colorimetric method, and HPLC, respectively. In vitro dissolution and antioxidant activity were determined by the paddle method in phosphate buffer (pH 6.8) and the DPPH radical scavenging method, respectively. In addition, the liver tissue pathology was evaluated by hematoxylin and eosin staining (H&E), and the AST and ALT activities were measured by automatic biochemical analyzer. The superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities were measured by using commercial analysis kits. Results: As the particle size decreases, the fluidity of TDG powders decreased and the porosity increased. In addition, there were no significant differences in physical properties between low temperature pulverized powders and room temperature pulverized powders. The final dissolution rates of the four bioactive ingredients in TDG-MP were found to be 85.06%, 85.61%, 83.88%, and 83.26%, respectively, whereas in TDG-CP, the dissolution rates were significantly lower at 18.79%, 17.96%, 22.46%, and 24.35%. The EC50 values of TDG-CP, TDG-FP, and TDG-MP on DPPH scavenging activity were 0.82, 0.31, and 0.10 mg/mL, respectively. The AST and ALT activities of the TDG-FP group and the TDG-MP group were significantly decreased and the SOD, CAT, and GSH activities were significantly increased when compared with that of the model group. The inflammatory cell infiltration and vacuolar degeneration of liver cells in the TDG-FP group and the TDG-MP group were significantly improved. Conclusions: The particle size of TDG powders had a significant effect on the physical properties and in vivo bioactivity. TDG pulverized to a fine particle size or smaller is a promising approach for clinical applications with improved physicochemical and biological properties.

Ferulic Acid Alleviates Lipid and Bile Acid Metabolism Disorders by Targeting FASN and CYP7A1 in Iron Overload-Treated Mice

Iron overload is a common complication in various chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD). Lipid and bile acid metabolism disorders are regarded as crucial hallmarks of NAFLD. However, effects of iron accumulation on lipid and bile acid metabolism are not well understood. Ferulic acid (FA) can chelate iron and regulate lipid and bile acid metabolism, but its potential to alleviate lipid and bile acid metabolism disorders caused by iron overload remains unclear. Here, in vitro experiments, iron overload induced oxidative stress, apoptosis, genomic instability, and lipid deposition in AML12 cells. FA reduced lipid and bile acid synthesis while increasing fatty acid β-oxidation and bile acid export, as indicated by increased mRNA expression of PPARα, Acox1, Adipoq, Bsep, and Shp, and decreased mRNA expression of Fasn, Acc, and Cyp7a1. In vivo experiments, FA mitigated liver injury in mice caused by iron overload, as indicated by reduced AST and ALT activities, and decreased iron levels in both serum and liver. RNA-seq results showed that differentially expressed genes were enriched in biological processes related to lipid metabolism, lipid biosynthesis, lipid storage, and transport. Furthermore, FA decreased cholesterol and bile acid contents, downregulated lipogenesis protein FASN, and bile acid synthesis protein CYP7A1. In conclusion, FA can protect the liver from lipid and bile acid metabolism disorders caused by iron overload by targeting FASN and CYP7A1. Consequently, FA, as a dietary supplement, can potentially prevent and treat chronic liver diseases related to iron overload by regulating lipid and bile acid metabolism.

Palmitoleic Acid Inhibits Hepatotoxic Effects by Reducing Trimethylamine-N-Oxide (TMAO) Formation in High L-Carnitine-Treated Mice

Background/Objectives: This study investigated the effects of palmitoleic acid (POA) consumption on liver function, intestinal microbiota, and trimethylamine-N-oxide (TMAO) levels in the serum of mice treated with 3% L-carnitine drinking water. The purpose was to highlight the impact of POA on liver injury associated with high L-carnitine intake. Methods: A correlation analysis was carried out. The physiological and biochemical results showed that the administration of POA could alleviate liver injury induced by high L-carnitine ingestion, as reflected by a reduction in liver function indices (ALT, AST, AKP, and TBA activities) and modulation of antioxidant enzyme activities (SOD, GSH-Px, MDA, and RAHFR). The study also monitored the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Additionally, to assess the impact of POA on intestinal microbiota, we conducted a 16S rRNA high-throughput sequencing analysis. Results: The findings indicated that POA administration resulted in lower levels of TMAO in treated mice. Furthermore, POA could regulate the composition of intestinal microbiota in L-carnitine mice, particularly affecting Bacteroides vulgatus, Parabacteroides distasonis, Alistipes shahii, Lachnospiraceae NK4A136 group, and Parasutterella secunda, which were closely related to liver injury. Conclusions: In summary, POA could repair liver damage caused by high intake of L-carnitine by regulating the distribution of intestinal flora and subsequently decreasing serum TMAO levels.

Acute and sub-acute toxicity study of aqueous and methanol root extract of Tetracera alnifolia in male albino rats

The aim of this study was to assess the acute and sub-acute toxicity of aqueous and methanol extracts of the root of Tetracera alnifolia as well as the effects on some biochemical parameters in albino rats as many plants used in traditional medicine lack scientific and clinical evidence to support a better understanding of their safety and efficacy. Phytochemical screening and proximate analysis of the pulverised root of Tetracera alnifolia was carried out using previously reported protocol. Sub-acute toxicity study of each extract was done for 28 days followed by organs function tests and histopathology studies of the liver, kidney and heart. Evaluation of lipid profile and oxidative stress marker to ascertain the effect of each extract on lipid peroxidation and their antioxidant property was done after administration of 200 mg/Kg body weight of each extract for a period of thirty-five days. Acute toxicity study of each extract gave oral LD50 (rat) of greater than 5000 mg/kg body weight with no signs of toxicity. Sub-acute toxicity study showed both extracts were non-toxic to the liver, kidney, heart and blood at doses between 200 and 3000 mg/Kg body weight assessed by the respective organ function tests, hematological parameters, and histopathology study. However, higher doses seem toxic to the liver particularly at 5000 mg/kg B. W due to increase in plasma AST, ALT and ALP activities accompanied with reduced protein and albumin concentrations. Effects of each extracts at 200 mg/Kg body weight on some biochemical parameters revealed no significant difference in lipid profile parameters and no lipid peroxidation. Each extract may possess antioxidant property due to increase in catalase activity. The result from this research may help validate the safety of the oral use of this plant in traditional medicine.

Histomorphological effects of ß,Ɛ-Carotene-3,3’-diol on the liver following indomethacin-induced hepatotoxicity in adult male Wistar rats

Medicinal plants are globally used as food and in the management of different ailments based on their peculiar phytochemical contents. This study aimed to evaluate the histomorphological effects of ß,Ɛ-Carotene-3,3’-diol on the liver following indomethacin-induced hepatotoxicity in adult male Wistar rats. This is to determine the ameliorative effect of graded doses of ß,Ɛ-Carotene-3,3’-diol. A total of twenty-five adult Wistar rats were randomly divided into five groups (n=5). Liver injury was induced by oral administration of 20 mg/kg b.w of indomethacin after 24 hours fast to animals in groups B-E. Twenty four hours after the induction, animals in groups C-E were given different doses of ß,Ɛ-Carotene-3,3’-diol. At the end of the experimentation, the animals were sacrificed and the livers were collected and fixed for histopathological and histomorphological analyses. The results showed that indomethacin increased the activities of AST, ALT and ALP and also induced histopathological changes. Treatment with ß,Ɛ-Carotene-3,3’-diol was able to attenuate liver injury caused by indomethacin in a dose dependent manner as evidenced in the histoarchitectural changes. This was also corroborated by the histomorphometric analyses. In conclusion, the results suggested the positive influence of ß,Ɛ-Carotene-3,3’-diol in ameliorating liver injury caused by indomethacin and by extension, may be adopted in the management of liver related injury.

Hepatoprotective Activity of Gingko biloba‐Mediated TiO2 NPs Against Acetaminophen‐Induced Albino Rats‐ In Vitro Studies

AbstractNumerous effects of “titanium dioxide nanoparticles (TiO2 NPs)” have been described and significantly utilized in complementary drugs for many decades. This study is conducted to analyze the therapeutic efficiency of TiO2 NPs against the acetaminophen‐(AMP) induced toxicity. TiO2 NPs were initially prepared using Ginkgo biloba leaf extract as reducing and stabilizing agent. The prepared TiO2 NPs were studied using various spectroscopic and microscopic techniques. AFM, TEM, XRD, and DLS studies have confirmed the formation of TiO2 NPs with size between 20 to 60 nm with negative surface charge of about −12 mV. Later, hepatoprotective studies were performed by administering AMP to albino mice only once at a dosage of 2 g/kg p.o. Post 24 h of AMP intoxication, the animals were treated orally with three different doses of TiO2 NPs (150, 100, and 50 mg/kg) or silymarin at an amount of 50 mg/kg p.o., administered only once. Post 24 h of last treatment, all the animals were surrendered to death. The group of mice administered with AMP displayed a substantial raise in the serum alkaline phosphatase (560 ± 31.90), lactate dehydrogenase (167 ± 10.17), aspartate amino transferase (251 ± 14.82), alanine amino transferase (326 + 18.96), bilirubin (2.2 ± 1.066), cholesterol (96.7 ± 6.2), and albumin (6.0 ± 1.27) in serum, which signified the liver damage. A considerably depleted level of glutathione (5.4 + 1.24) was detected in the mice intoxicated with AMP. The activities of catalase (33.2 ± 2.66) and superoxide dismutase (36 ± 2.93) declined after exposure to acetaminophen, resulting in oxidative stress in liver. The performance of adenosine triphosphatase (901 ± 50.7) and glucose‐6‐phosphatase (3.9 + 1.15) were considerably inhibited after administrating with AMP. On treating with TiO2 NPs, all the variables reversed significantly towards regular levels and were noticed to be nontoxic. The groups treated with TiO2 NPs exhibited less activity of ALT, AST, LDH, and SALP in serum, indicating the protective effect of TiO2 NPs to prevent liver damage. Exposure with TiO2 NPs inverted the cholesterol, albumin, and bilirubin levels towards normal, which is similar to silymarin treatment. TiO2 NPs exhibited a substantial change in tissue and blood biochemical parameters with that of control groups. These results indicate that TiO2 NPs possesses hepatoprotective properties that mitigate the hepatotoxicity induced by acetaminophen in rats. Hence, TiO2 NPs can be further utilized in the preparation of medicine against hepatic and renal diseases, post further clinical and preclinical studies.

Effects of a potential host gut-derived probiotic, Bacillus amyloliquefaciens AV5, on the growth, biochemical and metabolic responses, and disease resistance of Nile tilapia (Oreochromis niloticus)

The influence of the dietary probiotic Bacillus amyloliquefaciens AV5 on the growth, biochemical and metabolic responses, and disease resistance of Nile tilapia (Oreochromis niloticus) was evaluated. The commercial diet (GC), a diet containing 106 and 108 CFU/g of B. amyloliquefaciens AV5, denoted as G1 and G2, respectively, was fed for 30 days. Fish were allocated to 9 plastic tanks, and each diet was randomly assigned to triplicate groups of 40 fish (22.4 ± 1.3 g).After 30 days of the feeding trial, the specific growth rate, weight gain rate, and final weight increased significantly in G2 compared to those in GC and G1. Feed conversion ratio was significantly higher in the fish-fed GC group than in the G2 group. However, the survival rate of the fish ranged from 99.13 % to 97.17 %, with no significant difference. Glucose levels did not differ significantly (P < 0.05). Total antioxidant capacity (T-AOC), (superoxide dismutase (SOD), and catalase (CAT), as well as digestive enzymes (trypsin, lipase, and protease), were significantly increased in the G2 group relative to the GC and G1 groups.Significantly lower ALT, AST, CHO, TG, and MDA activities were observed in the G2 group than in the GC group. To evaluate the metabolomic response, PCA, OPLS-DA, and volcano plots revealed a distinct difference between the G2 and GC diets, suggesting that the G2 diet impacted the hepatopancreas of fish. Furthermore, challenge experiments revealed that fish fed B. amyloliquefaciens AV5 exhibited substantially increased resistance (P < 0.05) to S. agalactiae at a concentration of 1x108CFU/g. Therefore, dietary supplementation with B. amyloliquefaciens AV5 enhanced the growth performance, metabolic activity, and disease resistance of O. niloticus.

Toxicological evaluation of a herbal tea made from the leaves of Setaria megaphylla, Ageratum conyzoides and Chromolaena odorata

The toxicological effect of an herbal tea made from leaf extracts of Ageratum conyzoides, Chromolaena odorata, and Setaria megaphylla, plants traditionally used in Nigeria for malaria treatment was studied. Hot aqueous extracts of the ternary combination (1:1:1 ratio) of the plants were administered in varying doses (0, 50, 100, and 200 mg/kg) to assess impact on hepatic, renal and haematologic function parameters, and liver and kidney tissue histology of forty male albino rats divided into four groups of ten animals each. The tea extracts were administered orally daily for 60 days. Biochemical analyses revealed that the extract significantly (p&lt;0.05) reduced ALT (25.91 ± 2.35 to 6.84 ± 0.31 U/L), AST (36.39 ± 1.96 to 19.24 ± 1.19 U/L), and ALP (21.94 ± 3.51 to 11.06 ± 2.76 IU/L) activities, with no significant (p&gt;0.05) changes in bilirubin, protein and albumin concentrations, suggesting non-hepatotoxic property. Among the kidney function, significant (p&lt;0.05) dose-dependent increases was observed only in serum urea ranging from 23.09 ± 0.79 mg/dl (Control group) to 34.90 ± 0.52 mg/dl (200 mg/kg treated group). Increase in WBC count was observed indicative of a possible immune response, while other blood parameters remained stable. Histopathological examination confirmed that lower extract doses were relatively safe, whereas higher doses presented early signs of organ stress. These findings suggest that this herbal tea extract has a favourable safety profile at moderate doses, though higher doses may pose risk of organ toxicity, warranting further studies on dose optimization and elucidation of its folkloric therapeutic potential.

Association of Firmicutes/Bacteroidetes Ratio with Body Mass Index in Korean Type 2 Diabetes Mellitus Patients.

The gut microbiome, which is the collection of microorganisms living in the gastrointestinal tract, has been shown to play a significant role in the development of metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Studies have found that the ratio of Firmicutes to Bacteroidetes (F/B) is higher in obese individuals compared to lean individuals and tends to decrease with weight loss. However, the relationship between the F/B ratio and T2DM in Korean individuals, with or without obesity, is not fully understood. The objective of this study is to compare the F/B ratios and metabolic profiles of lean and obese Korean individuals with T2DM. In this study, 36 individuals with type 2 diabetes mellitus (T2DM) were recruited and classified into four groups (I, II, III, and IV) based on their body mass index (BMI). Group I had a BMI of less than 23.0, group II had a BMI between 23.0 and 24.9, group III had a BMI between 25.0 and 29.9, and group IV had a BMI of 30 kg/m2 or greater. Fecal samples were collected from all participants and sent to Chunlab Inc. (located in Seoul, Republic of Korea) for analysis. The changes in the major microbial phyla within the samples were investigated using quantitative real-time PCR. The collected data were then statistically analyzed using the SPSS program. The levels of triglycerides and alanine transaminase in group I were significantly lower than in the other three groups. The amount of Actinobacteria in group IV was the highest among all four groups. The ratio of Firmicutes to Bacteroidetes increased as BMI increased, and this ratio was positively correlated with AST activity. Our study showed that there is a correlation between the degree of obesity in individuals with diabetes and their gut microbiome. Additionally, the ratio of Firmicutes to Bacteroidetes (F/B ratio) may play a role in the metabolic effects of fatty liver disease, as it may contribute to obesity.

Oct-B: A derivative of L-BAIBA significantly alleviating high-fat diet-induced obesity in mice

The rising prevalence of obesity is a global health concern. Supplementation with (S)-β-aminoisobutyric acid (L-BAIBA) has shown potential in preventing obesity and related metabolic disorders induced by high-fat diets. However, developing effective and low-toxicity BAIBA derivatives remains a challenging yet promising field. In this study, we introduce Oct-B, a novel BAIBA ester compound, which exhibits 80-fold greater efficacy than L-BAIBA in alleviating obesity in high-fat diet-fed mice. Our results demonstrate that Oct-B significantly reduces serum TG, TC, LDL-C, and the activities of ALT and AST, and also reduces TG and TC in liver, surpassing the effects of L-BAIBA. Histological analysis shows that Oct-B significantly decreases lipid accumulation in liver tissues, normalizes mast cells in white adipose tissue, and upregulates the expression of UCP1 protein in white adipose tissue. The qRT-PCR results indicated Oct-B alleviates obesity by downregulating lipogenic genes (PPARγ, ACC1, FAS), upregulating lipolysis related genes (PPARα, HSL) and thermogenic gene UCP1. Additionally, quantitative mass spectrometry reveals a marked increase in L-BAIBA levels in white fat, brown fat, serum, and muscle following Oct-B administration. These findings suggest that Oct-B is an efficient L-BAIBA substitute, offering a promising therapeutic approach for preventing and treating high-fat diet-induced obesity.

Mitigating impact of Glycyrrhiza glabra on virulent Newcastle disease virus challenge in chickens: clinical studies, histopathological alterations and molecular docking.

Newcastle disease (ND) is widely regarded as one of the most virulent and destructive viral infections that create chaos in the poultry industry and cause widespread epidemics and consequentially debilitating economic losses on a global scale in terms of chicken products. The current experiment evaluates the protective effect of Glycyrrhiza glabra ( G. glabra) against the Newcastle disease virus (NDV) in chickens. Ninety (90) 1-day-old SPF chicks were treated according to ethical approval (BUFVTM 05-02-22) as follows (1) non-treated non-challenged control group; (2) NDV group: Challenged with genotype VII ND virus; and (3) LE/NDV group: Challenged with the virus and intermittently treated with powdered extract of G. glabra roots (LE) in drinking water (0.5g/L) before and after viral challenge. The water medication of NDV-challenged chicks has resulted in a significant decrease in the severity of clinical symptoms, morbidity, and mortality rates, as well as the quantity of virus shed, compared with the NDV group. Treatment with LE has led to a significant reduction in serum ALT and AST activities, blood glucose level, urea, and creatinine, and significant restoration of serum proteins. In addition, the treatment has resulted in a decrease in MDA and NO levels, as well as an increase in T-SOD and catalase activities compared with untreated challenged chicks. LE decreased IFN-γ and TLR-3 gene expression in comparison with the NDV group. The treated challenged birds had fewer macroscopically detectable lesions in their respiratory, digestive, and lymphoid organs than the untreated challenged birds. Microscopically, the LE/NDV group exhibited mild to moderate pathological changes in the respiratory and digestive systems as well as lymphoid tissues, in contrast to the NDV group, which exhibited severe pathological changes. Furthermore, molecular docking assessment proved the efficacy of G. glabra against viral proliferation and invasion. We concluded that Glycyrrhiza glabra powdered extract at a dose of 0.5g/L drinking water can effectively mitigate the debilitating effects of Newcastle disease in chickens.

High efficacy and safety of direct-acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha-fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well-tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.

Hepatic and immune modulatory effectiveness of lactoferrin loaded Selenium nanoparticles on bleomycin induced hepatic injury

This study aimed to estimate the hepatic and immune ameliorating potential of extracted bovine lactoferrin (LF), Selenium nanoparticles (SeNPs) or their combination (LF/SeNPs) against bleomycin (BLM) induced hepatic injury. Fifty adult male rats (160–200 g) were equally divided into five groups: (1) the saline control group, (2) BLM-injected (15 mg/kg twice a week, ip), and (3–5) groups treated orally with LF (200 mg/kg/day), SeNPs (0.0486 mg/kg/day) or LF/SeNPs combination (200.0486 mg/kg/day) for 6 weeks post BLM-intoxication. Blood and liver samples were subjected to biochemical, histopathological, and immunohistochemical analyses. The results revealed that BLM caused a significant increase in hepatic lipid peroxidation and nitric oxide, as well as serum markers of liver functions (AST, ALT and GGT activities), and levels of GM-CSF, CD4, TNF-α, IL-1β, TGF-β1, fibronectin, triglycerides, cholesterol and LDL-C. Additionally, hepatic glutathione, Na+/K+-ATPase, and glutathione peroxidase, as well as serum HDL-C, total protein and albumin levels were significantly reduced. Moreover, BLM injection resulted in marked histopathological alterations and severe expression of caspase 3. Post-treatment of BLM-intoxicated rats with LF, SeNPs or LF/SeNPs combination obviously improved the BLM-induced hepatic damages; this was achieved from the marked modulations in the mentioned parameters, besides improving the histopathological hepatic architecture. It is worth mentioning that LF/SeNPs exerted the greatest potency. In conclusion, the obtained results demonstrated that LF, SeNPs and LF/SeNPs succeeded in attenuating the BLM-induced hepatic dysfunction. Therefore, these supplements might be used to protect against drug-associated side effects.

ВПЛИВ МІКОТОКСИНУ Т-2 НА ІХТІОЛОГІЧНІ ПОКАЗНИКИ КОРОПОВИХ РИБ

Mycotoxins are particularly dangerous for both animals and humans. Their toxic effects manifest even in ultra-minimal doses, which are often impossible to detect even with modern methods. The response mechanism of hydrobionts to toxic pollution in the aquatic environment is revealed through biochemical and physiological reactions aimed at restoring damaged functions. Increased human impact on aquatic ecosystems has exacerbated the survival challenges for aquatic organisms under stressful conditions. A study was conducted to investigate the impact of mycotoxin T-2 on ichthyological indicators in carp fish. Even ultra-low doses of mycotoxins can have toxic effects, and their presence is often difficult to detect with modern methods. Changes in morphometric indicators and metabolic processes are integral components of complex nonspecific reactions that occur in response to any stress factors. During long-term exposure or at high intensity, serious and irreversible damage can occur, potentially leading to various pathologies or even death of the organism. Based on this, the aim of the study was to examine the effect of mycotoxin T-2 on the ichthyological indicators of carp fish. A laboratory experiment showed that exposure to mycotoxin T-2 led to a slight increase in the fatness ratio of fish, which could be explained by tissue swelling. A similar trend was observed regarding the liver index in carp. In the case of crucians, the liver index remained unchanged. Additionally, no significant changes were found in the indicators of body height, head height, and compactness. This can be attributed to the relatively short two-week experimental period, which may not be sufficient to detect differences in morphological parameters. During the experiment, when mycotoxin T-2 was introduced into laboratory aquariums, changes were detected in the protein metabolism components in the blood of fish. Total protein levels decreased by 29% in carp and 32% in crucian carp exposed to mycotoxin T-2. The study of ALT and AST activity in the blood under the influence of mycotoxin revealed an increase in the activity of aminotransferases in both carp and crucian carp. From the blood, free amino acids are transferred to the liver, where in response to ALT and AST, their transamination increases, explaining the heightened activity of these enzymes.

Effects of Bacillus subtilis on Growth Performance, Metabolic Profile, and Health Status in Dairy Calves.

This study focused on assessing whether the inclusion of probiotics (B. subtilis) as feed additives during the preweaning stage can enhance the body weight and metabolic condition of neonatal calves. A total of 50 Holstein calves, all born on the same farm, were randomly divided into two homogeneous treatment groups after birth. The calves in the control group (CG) were fed a milk replacer (n = 25) (13 females and 12 males) and those in the B. subtilis-supplement-treated group (TG), (n = 25) (13 females and 12 males) were fed a milk replacer with 7.5 mL/calf/day of B. subtilis probiotic (complied with the manufacturer's guidelines). The probiotic was administered 24 h post-birth, signifying the start of the experimental period. It took one month to collect the animals. Body weight was measured at birth for all animals. A local veterinarian, working on the farm, conducted daily health checks of the calves, recording health parameters and any antibiotic treatments. Blood samples were collected from each calf at birth and 30, 60, and 90 days by puncturing the jugular vein using 10 mL evacuated serum tubes before morning feeding. Significant differences in body weight were observed between the CG and the TG at 30, 60, and 90 days of age. At 30 days, the TG had a 4.11% higher average body weight than the CG (54.38 kg vs. 52.71 kg). At 60 days, the TG's average weight was 3.75% higher (79.21 kg vs. 76.34 kg), and at 90 days, the TG had a 2.91% higher average weight (112.87 kg vs. 109.67 kg). At 30 days of age, the TG showed significantly lower AST activity, with a 41.12% decrease compared to the CG (51.02 IU/L vs. 72.00 IU/L). Conversely, GGT activity was significantly higher in the TG by 64.68% (40.64 IU/L vs. 14.35 IU/L). Phosphorus concentration at 30 days was also significantly higher in the TG by 9.36% (3.27 mmol/L vs. 2.99 mmol/L). Additionally, the TG had a significantly lower total protein concentration, with a 21.63% decrease at 30 days (46.32 g/L vs. 56.34 g/L) and a 20.28% decrease at 60 days (48.32 g/L vs. 58.12 g/L) compared to the CG. These findings indicate that dairy calves given conventional milk replacer along with a daily dose of 7.5 mL of B. subtilis probiotic experienced enhanced growth performance and a more favourable metabolic profile during the first 90 days of their lives.

Elucidating the effect of dietary neem (Azadirachta indica) on growth performance, haemato-biochemical, immunonological response, and anti-pathogenic capacity of Nile tilapia juveniles.

This investigation attempts to evaluate the effect of diet additives via aqueous or ethanolic herbal extracts from Azadirachta indica leaves on Nile tilapia, Oreochromis niloticus. Five dietary categories were assigned to the fish: the first category (N1, with no extract) was kept under control conditions; two categories contained aqueous extract (N2 (1.0g/kg) and N3 (2.0g/kg); and two categories contained ethanolic extract, N4 (1.0g/kg) and N5 (2.0g/kg), with each group being fed for 60 days. After the feeding trial, Aeromonas hydrophila was injected intraperitoneally into fish for 14 days; fish mortality was recorded during this period. The results showed that the fish-fed dietary A. indica significantly improved growth performance and intestinal health (digestive enzymes and intestinal morphology), especially in the N4 and N5 categories. However, N4 and N5 categories demonstrated a significant decrease in AST and ALT activities and an increase in total protein, serum albumin, globulin, growth hormone (GH), leptin hormone (LEP), hemoglobin, white blood cells, and hematocrit (P < 0.05) in comparison with the control category (N1). Compared to the control category, the N4 and N5 categories have revealed a significant reduction in MDA activity and improvements in immunological activities (lysozyme, complement C3, and nitric oxide) and antioxidant enzymes (CAT, SOD, and GPX). Moreover, in tilapia-fed A. indica, the expression of IL-8, IL-1β, and Nf-κb genes was downregulated partially in the N4 and N5 categories than the control category. In contrast, the lysozyme, C3, GPX, and CAT genes were upregulated partially at N4 and N5 compared to the control category. Following the bacterial challenge, fish in the N4 and N5 categories also displayed the lowest fish mortality compared to the control category. The ethanolic extract displayed a more potent resistance against the parasite Cichlidogyrus tilapia in vitro than the aqueous and control categories, partially at 2g/L. According to these findings, an ethanolic neem extract (2.0g/kg feed) activates the immune system and antioxidant response in Nile tilapia fingerlings, improving growth and fish resistance to parasitic and bacterial infections.

Sunitinib alleviates hepatic ischemia reperfusion injury by inhibiting the JAK2/STAT pathway and promoting the M2 polarization of macrophages

Background Hepatic ischemia reperfusion injury (IRI) is a common liver surgery complication. This study aims to explore the effect and potential mechanism of Sunitinib – a multi-target tyrosine kinase inhibitor – on hepatic IRI. Methods We established a hepatic IRI model using C57BL/6 mice, and integrated 40 mg/kg of Sunitinib, solely or combined with 100 μg/kg of coumermycin A1 (C-A1), in the treatment strategy. H&E staining, TUNEL assay, and detection of serum ALT and AST activities were used to assess liver damage. Further, ELISA kits and Western Blots were utilized to determine IL-1β, TNF-α, IL-6, CXCL10, and CXCL2 levels. Primary macrophages, once isolated, were cultured in vitro with either 2 nM of Sunitinib, or Sunitinib in conjunction with 1 μM of C-A1, to gauge their influence on macrophage polarization. qPCR and Western blot were conducted to examine the level of p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2, and M1/M2 polarization markers. To quantify immune cell infiltration, we applied Immunofluorescence. Results Sunitinib pretreatment significantly alleviated liver injury and reduced p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2 levels. In vitro, Sunitinib treatment curbed M1 polarization induced by LPS + IFN-γ and bolstered M2 polarization triggered by IL-4. C-A1 application upregulated JAK2/STAT pathway phosphorylation and promoted LPS + IFN-γ-induced M1 polarization, which was reversed by Sunitinib treatment. In IL-4-stimulated macrophages, application of C-A1 activated the JAK2/STAT pathway and decreased M2-type macrophages, which was reversed by Sunitinib treatment either. Conclusion Sunitinib is capable of guiding the polarization of macrophages toward an M2-type phenotype via the inhibition of the JAK2/STAT pathway, thereby exerting a protective effect on hepatic IRI.

Is hyperammonemia helpful in detecting syndromic tubulopathies with early extrarenal manifestations? A case report of Lowe’s syndrome

BackgroundGenerally, it is not well known that Lowe’s syndrome may coexist with hyperammonemia and hipocarnitynemia. The importance of hyperammonemia in the diagnosis of kidney diseases is not completely understood.Case presentationWe present the history of a 13-year-old boy, admitted to the hospital due to proteinuria. In the past, the boy was diagnosed with binocular cataracts in infancy. Then he went through neurological diagnostic tests which diagnosed muscular hypotonia and psychomotor retardation but no inherited errors of metabolism were found. Proteinuria has been observed since the age of 2. Ultrasound imaging at the age of 5 showed the presence of a shading deposit in the kidney. At the age of 13, the boy was referred to the Pediatric Nephrology Ward. The laboratory tests revealed: a reduction of glomerular filtration rate, metabolic acidosis, proteinuria, hypercalciuria, increased activity of AST (SGOT), CK, LDH, hyperammonemia, and decreased concentration of total carnitine in blood serum. Based on the clinical presentation, Lowe’s syndrome was diagnosed. The genetic testing revealed an OCRL gene hemizygous mutation.ConclusionLowe’s syndrome is an example of a disease in which clinical symptoms—although occurring early and in high intensity—may not raise the suspicion of tubulopathy for a long time if they are not analyzed in a complex manner. There is a necessity to educate healthcare practitioners from other fields about the extrarenal symptoms of genetically determined tubulopathies.l-carnitine deficiency may be a symptom of proximal tubulopathy, including Lowe’s syndrome. l-carnitine deficiency leads to disturbances in the efficiency of the urea cycle, which results in hyperammonemia. Hyperammonemia is not only a symptom of inborn errors of metabolism and liver failure, but it may also lead to the diagnosis of tubulopathy.Since carnitine supplementation could have the desired beneficial effect on the patient’s general condition, it is postulated to conduct further studies on larger groups of patients with Lowe’s syndrome.

Effect of Age on the Biochemical and Hematological Blood Profile in the Arabian Horses Raised in Libya

Normal hematological and biochemical values need to be defined for each equine age in order to increase diagnostic precision. The present study was aimed to monitor the hematobiochemical characteristics of 65 clinically healthy Arabian horses raised in Libya with an age of less than or equal 3 years (young) or more than 3 years (stallion). The results showed that MCHC were significantly (p&lt;0.0001) higher in the young horses than stallions, while the reverse for HCT, MCV, RDW-CV, RDW-SD, and MPV. On the other hand, Hb, RBC, MCH, PDW and PCT showed non-significant change with the variations between Arabian horse's ages. The total leukocyte and platelet counts were statistically increased in young horses but did not significantly different. Regarding activities of different enzymes (ALT, AST, ALP and LDH activity), there are significantly (p&lt;0.05) increased values in young horses compared with stallions. However, the serum TP, TB and DB were significantly (p&lt;0.005) higher in adult horses than young one. There are significant and non-significant differences in some lipid profile and electrolytes between animals according to age factor. In abbreviate, results of this study showed that both blood and biochemical parameters clearly alterated under the effect of age in this breed of horses.