Enzymes Alanine Aminotransferase Research Articles

Preliminary study on the diagnostic value of LEAP-2 and CK18 in biopsy-proven MAFLD

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has become the leading cause of chronic liver disease. Liver biopsy, as the diagnostic gold standard, is invasive and has sampling bias, making it particularly important to search for sensitive and specific biomarkers for diagnosis. Cytokeratin 18 (CK18) M30 and M65 are products of liver cell apoptosis and necrosis, respectively, and liver-expressed antimicrobial peptide 2 (LEAP-2) is a related indicator of glucose and lipid metabolism. Correlation studies have found that all three indicators positively correlate with the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Through comparison of diagnostic values, it was found that CK18 M65 can better distinguish between healthy individuals and MAFLD; LEAP-2 can effectively distinguish MAFLD from other liver diseases, especially ALD.

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.

Evaluation of Some Liver Enzymes in HIV/AIDS Patients on Antiretroviral Therapy in University of Abuja Teaching Hospital, Nigeria

Background: Hepatoxicity is a major complication and side effect of antiretroviral therapy (ART). Unfortunately, such studies in this area of evaluating the adverse drug reaction of ART on the liver hepatocytes are only few in number in Nigeria.Objective: To determine the levels of some liver enzymes in HIV/AIDS patients on antiretroviral therapy (ART) and as well evaluate their impact on liver hepatocytes.Methods: This is a hospital-based case-control study. A total of 153 subjects were recruited in the study, and they were divided into three groups: the control group (which consist of apparently healthy subjects), the study group 1 (consist of HIV positive subject not on ART), and study group 2 (consist of HIV/AIDS patients on ART). The liver enzymes Alanine amino Transferase (ALT), Asparate amino Transfarase (AST) and Alkaline Phosphatase (ALP) were determined using enzyme linked spectrophotometric assay methods, according to the manufacturer’s specifications.Results: The mean standard deviation (SD) of ALT and AST activity of the study group 1 showed significant differences when compared with that of the control group P<0.001, but the ALP has no significant differences P>0.05. In Study group 2, (HIV/AIDS patients on ART) showed significant differences of P<0.001 in ALT, AST and ALP.Conclusion: Some liver enzymes were elevated in subjects on antiretroviral therapy; this elevation could be due to hepatotoxicity of the (ART) used by the HIV/AIDS patients on the liver hepatocytes.International Journal of Human and Health Sciences Vol. 08 No. 02 Apr’24 Page: 126-131

Exploring the effects of ursodeoxycholic acid-probiotic combination on Lactobacillus and liver enzyme levels for cholestasis management: An experimental study

Background: Cholestasis arises from compromised bile secretion due to hepatocyte dysfunction, leading to liver impairment. Available treatments show limited efficacy, with ursodeoxycholic acid (UDCA) being a primary option. Cholestatic conditions influence gut microbiota; therefore, probiotic therapy emerges as a potential approach. Objective: This investigation aimed to evaluate the impact of combined administration of probiotics and UDCA on Lactobacillus levels, as well as the levels of the enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats with restricted common bile ducts .Methods: A total of 35 male Sprague Dawley rats were randomly assigned to 7 groups, each comprising 5 members: K1 (healthy control), K2 (negative control with cholestasis), K3 (positive control with cholestasis given UDCA), K4 (cholestasis given 36 mg probiotics), K5 (cholestasis given 18 mg probiotics and UDCA), K6 (cholestasis given 36 mg probiotics and UDCA), and K7 (cholestasis given 54 mg probiotics and UDCA). The treatment duration was 21 days, during which blood samples were collected for AST and ALT analysis. Lactobacillus count was determined by quantitative polymerase chain reaction (PCR) analysis of fecal samples.Results: When UDCA and probiotics were given together in three different dosages, the Lactobacillus count significantly increased (p<0.05) compared to the other groups. Furthermore, compared to the other treatment groups, the UDCA-probiotic combination group exhibited noticeably lower AST and ALT values.Conclusion: Combining UDCA and probiotics elevated Lactobacillus count and decreased AST and ALT levels in cases of cholestasis more effectively than single therapy.

The Role of Oxidative Stress in Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies.

Alcoholic Fatty Liver Disease (AFLD) is characterized by the accumulation of lipids in liver cells owing to the metabolism of ethanol. This process leads to a decrease in the NAD+/NADH ratio and the generation of reactive oxygen species. A systematic review and meta-analysis were conducted to investigate the role of oxidative stress in AFLD. A total of 201 eligible manuscripts were included, which revealed that animals with AFLD exhibited elevated expression of CYP2E1, decreased enzymatic activity of antioxidant enzymes, and reduced levels of the transcription factor Nrf2, which plays a pivotal role in the synthesis of antioxidant enzymes. Furthermore, animals with AFLD exhibited increased levels of lipid peroxidation markers and carbonylated proteins, collectively contributing to a weakened antioxidant defense and increased oxidative damage. The liver damage in AFLD was supported by significantly higher activity of alanine and aspartate aminotransferase enzymes. Moreover, animals with AFLD had increased levels of triacylglycerol in the serum and liver, likely due to reduced fatty acid metabolism caused by decreased PPAR-α expression, which is responsible for fatty acid oxidation, and increased expression of SREBP-1c, which is involved in fatty acid synthesis. With regard to inflammation, animals with AFLD exhibited elevated levels of pro-inflammatory cytokines, including TNF-a, IL-1β, and IL-6. The heightened oxidative stress, along with inflammation, led to an upregulation of cell death markers, such as caspase-3, and an increased Bax/Bcl-2 ratio. Overall, the findings of the review and meta-analysis indicate that ethanol metabolism reduces important markers of antioxidant defense while increasing inflammatory and apoptotic markers, thereby contributing to the development of AFLD.

The 2023 Dengue Outbreak in Bangladesh: Exploring the Epidemiology in Hospitalized Patients.

For the past two decades, Bangladesh has faced recurrent dengue outbreaks, with the most recent occurring in 2023. We investigated the socioeconomic, clinical, and laboratory aspects of patients diagnosed with dengue during this outbreak. This observational study was conducted from July to September 2023 at Dhaka Medical College Hospital and Chittagong Medical College Hospital, and included 450 confirmed cases of dengue. Sociodemographic information was collected via face-to-face interviews, clinical examinations, and laboratory testing, which was done within 24 hours of admission. Dengue severity was classified according to the 2009 WHO dengue guidelines. Notably, 17% of patients experienced severe dengue, and 89% of those with nonsevere cases exhibited at least one warning sign. Most patients were young adults (mean age, 33 years), with a nearly equal male-to-female ratio. Common clinical presentations included fever (95%), myalgia (62%), and headache (58%), whereas warning signs such as vomiting (54%) and abdominal pain (39%) were prevalent. Plasma leakage indicators, including ascites, pleural effusion, and edema, were found predominantly in severe cases. Laboratory findings revealed leukopenia, thrombocytopenia, and elevated hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in nearly half the patients. An elevated hematocrit level was associated with severe dengue. We report that a substantial number of patients developed severe dengue during the epidemic in 2023, and provide detailed clinical-epidemiological profiles of the patients, offering valuable insight into management of dengue cases.

Individualized homeopathic medicines in preventing the progression from pre-diabetes to diabetes: A double-blind, randomized, placebo-controlled, parallel-arm trial

ContextPre-diabetes is a significant public health problem worldwide. India has a very high rate of progression from pre-diabetes to diabetes, 75–78 per thousand persons per year. ObjectiveTo study the efficacy of individualized homeopathic medicinal products (HMPs) against placebos in preventing the progression from pre-diabetes to diabetes. DesignSix-month, double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. SettingOutpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India. PatientsSixty participants with pre-diabetes. InterventionsVerum: HMPs plus yoga therapy (YT; n = 30); control: identical-looking placebos plus YT (n = 30). Main outcome measuresThe primary efficacy endpoint was the proportion of participants progressing from pre-diabetes to diabetes, measured after three and six months. Secondary outcomes comprised of fasting blood glucose (FBS), oral glucose tolerance test (OGTT), glycated hemoglobin percentage (HbA1c%), lipid profile, liver enzymes (alanine transaminase, aspartate transaminase), urea and creatinine, and Measure Yourself Medical Outcome Profile version 2 (MYMOP-2); all measured after 3 and 6 months. ResultsThe proportion of participants converted from pre-diabetics to diabetics (n/N; n = diabetics, N = prediabetics) was significantly less in the verum group than control: HbA1C% (month 3: verum – 2/30 versus control – 11/30, p = 0.003; month 6: 3/30 vs. 2/30, p = 0.008), OGTT (month 3: 0/30 vs. 8/30, p = 0.015; month 6: 0/30 vs. 1/30, p = 0.008), but not according to FBS (month 3: 1/30 vs. 1/30, p = 0.779; month 6: 1/30 vs. 3/30, p = 0.469). Several secondary outcomes also revealed significant improvements in the verum group than in placebo: HbA1C% (p < 0.001), OGTT (p = 0.001), serum ALT (p = 0.031), creatinine (p = 0.012), and MYMOP-2 profile scores (p < 0.001). Sulphur, Bryonia alba, and Thuja occidentalis were the most frequently indicated medicines. Thus, HMPs outperformed placebos by successfully preventing the progression of pre-diabetes to diabetes. Trial registrationClinical Trials Registry – India CTRI/2022/04/042,026; UTN: U1111–1277–0021

LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study

Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 μL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing. Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.

PROTECTIVE EFFECT OF GINGER (ZINGIBER OFFICINALE) AND CLOVE (SYZYGIUM AROMATICUM) AGAINST INDUCED HEPATOTOXICITY BY DIMETHOATE IN EXPERIMENTAL ANIMALS

Usage of pesticides is world wide spread have harmful effect on human health via environmental or occupational exposure, that pollute water, soil and food. This experimental study aims to investigate possible antioxidant and protective activities of ginger (Zingiber officinale) and clove (Syzygium aromaticum) aqueous extracts against induced injury of liver hepatocytes using the organophosphate Dimethoate (DM) in rabbits. Thirty adult male rabbits from local market were divided into five groups (6 animals in each). (1) control rabbits, (2) rabbits were given DM (20 mg/kg B. w daily dose 1/20 of half the lethal dose), (3) rabbits were given ginger extract (400 mg/kg B.W) daily dose and then DM, (4) rabbits were given clove extract (100 mg/kg B.W) daily dose and then DM, (5) rabbits were given ginger with clove extracts and then DM as previous dose for 30 days. At the end of the experiment animals were anesthetized and then sacrificed. The blood sample was collected for biochemical analysis. Dimethoate resulted in significant increase in the activity of aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) compared with control. Significantly increased level of both total and direct bilirubin were observed. However, the total protein and albumin were decreased. The ginger and clove extracts either separately or combined in groups 3,4 and 5 showed significantly improvement and decrease activity of liver enzymes AST, ALT and ALP. On the other hand, decreased in total bilirubin compared with DM group were recorded. While increased the serum levels of total protein and albumin were observed. It could be included that ginger and clove extracts were effective in protecting against induced hepatotoxicity by treating liver functions. Therefore, we recommend these two plants by moderate amounts to be added in the daily meals and drinks.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

The effect of thyme essential oil and endothelial progenitor stem cells on lipopolysaccharide-induced sepsis in C57BL/6 mice.

Sepsis is a potentially fatal syndrome related to severe systemic inflammation developed by infection. Despite different antimicrobial therapies, morbidity and mortality rates remain high. Herbs along with cell therapy have been introduced as a promising option to improve the symptoms of sepsis. The present study aimed to evaluate the therapeutic effect of simultaneous administration of thyme essential oil (TEO) and endothelial progenitor stem cells (EPCs) on lipopolysaccharide (LPS)-induced sepsis in C57BL/6 mice. Sepsis was induced in C57Bl/6J mice by intraperitoneal injection of LPS, followed 2h later by an intravenous injection of EPCs or oral administration of TEO or simultaneous administration of TEO and EPCs. After 10 days, the complete blood cell, renal and liver factors, serum levels of inflammatory cytokines, and angiogenic factors were measured. Simultaneous treatment with EPCs and TEO significantly increased the survival of mice with sepsis and modulated the inflammatory response by reducing the serum levels of pro-inflammatory cytokines. Moreover, this treatment significantly reduced the level of white blood cells and neutrophils and increased the number of red blood cells, the percentage of hematocrit, and hemoglobin. The combination of TEO with EPCs decreased organ injuries and was assessed by lower levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase compared to the sepsis group. Administration of EPCs and TEO also significantly improved angiogenic factors, lung function, and toll-like receptor 4 expression. EPCs in combination with TEO increase survival in the LPS-induced sepsis mice model by acting on several targets. Thus, the combination of TEO with EPCs can be a feasible approach for the future clinical treatment and control of sepsis.

Ammoniagenic Action of Valproate without Signs of Hepatic Dysfunction in Rats: Possible Causes and Supporting Evidence.

(1) Background: Valproic acid (VPA) is one of the frequently prescribed antiepileptic drugs and is generally considered well tolerated. However, VPA neurologic adverse effects in the absence of liver failure are fairly common, suggesting that in the mechanism for the development of VPA-induced encephalopathy, much more is involved than merely the exposure to hyperammonemia (HA) caused by liver insufficiency to perform detoxification. Taking into account the importance of the relationship between an impaired brain energy metabolism and elevated ammonia production, and based on the ability of VPA to interfere with neuronal oxidative pathways, the current study intended to investigate a potential regional ammoniagenic effect of VPA on rats' brains by determining activities of the enzymes responsible for ammonia production and neutralization. (2) Methods: Rats received a single intraperitoneal injection of VPA (50, 100, 250, 500 mg/kg). Plasma, the neocortex, the cerebellum, and the hippocampus were collected at 30 min after injection. The levels of ammonia, urea, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in blood plasma. The activities of glutaminase and glutamate dehydrogenase (GDH) in mitochondria and the activities of AMP deaminase (AMPD), adenosine deaminase (ADA), and glutamine synthetase (GS) in cytosolic fractions isolated from rat brain regions were measured. Ammonia, ALT, and AST values were determined in the mitochondrial and cytosolic fractions. (3) Results: Multi-dose VPA treatment did not significantly affect the plasma levels of ammonia and urea or the ALT and AST liver enzymes. Significant dose-independent increases in the accumulation of ammonia were found only in the cytosol from the cerebellum and there was a strong correlation between the ammonia level and the ADA activity in this brain structure. A significant decrease in the AMPD and AST activities was observed, while the ALT activity was unaffected. Only the highest VPA dose (500 mg/kg) was associated with significantly less activity of GS compared to the control in all studied brain structures. In the mitochondria of all studied brain structures, VPA caused a dose-independent increases in ammonia levels, a high concentration of which was strongly and positively correlated with the increased GDH and ALT activity, while glutaminase activity remained unchanged, and AST activity significantly decreased compared to the control in all studied brain structures. (4) Conclusions: This study highlights the rat brain region-specific ammoniagenic effects of VPA, which may manifest themselves in the absence of hyperammonemia. Further research should analyze how the responsiveness of the different brain regions may vary in VPA-treated animals that exhibit compromised energy metabolism, leading to increased ammoniagenesis.

Effects of Clothianidin on Biochemical Parameters of Adult Zebrafish

The ubiquitous use of insecticides leads to detrimental effects on non-target organisms due to accidental exposure. Neonicotinoid insecticides are popularly used worldwide for their high affinity for arthropod nicotinic receptors which effectively kill insect pests. Low affinity towards vertebrate nicotinic receptors, make them safer as compared to traditional insecticides. Recent studies demonstrated that neonicotinoid exposure can cause some toxicity in vertebrates including humans. Zebrafish is one of the popular model organisms to study ecotoxicity. This is the first study on adult zebrafish to report the effect of novel neonicotinoid, Clothianidin on mortality, liver antioxidant stress profile, liver function profile and brain acetylcholinesterase (AChE). Observations were made over two treatment periods, 96 hours, and 21 days, in five groups exposed to varying concentrations of Clothianidin viz. 30mg/L, 50mg/L, 70mg/L, 90mg/L, 110mg/L and a control. Although no mortality was observed, Clothianidin exposure led to increased activity of superoxide dismutase (SOD) enzyme, lipid peroxidation and decreased catalase (CAT), glutathione-S-transferase (GST). Treated groups also showed increased concentrations of liver enzyme alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP). These results indicate that Clothianidin causes disturbances in the hepatic function. A prominent decreasing trend observed in brain AChE shows that Clothianidin inhibits AChE in adult zebrafish. Further investigations on DNA damage and gene expression studies could be conducted to understand the exact mechanism of action of Clothianidin

Dietary Bacillus species modulate lipid metabolism-related parameters, growth, water quality, and bacterial load in Nile tilapia (Oreochromis niloticus )

This study examined the impact of supplementing Bacillus spp. mixtures at concentrations of 0.2 g/kg (PRO-0.2) and 0.5 g/kg (PRO-0.5) on Nile tilapia (Oreochromis niloticus) for 90 days. Fish groups receiving PRO-0.2 and PRO-0.5 exhibited significantly lower water ammonia levels than the control group, in linear and quadratic patterns. Furthermore, their length and weight increased exponentially over time, peaking at the end of the experiment. After 90 days, the PRO-0.5 group displayed the highest mean weight gain. Additionally, both the PRO-0.2 and PRO-0.5 groups had the lowest food conversion ratios and highest protein efficiency ratios in a linear pattern. They also showed improved liver function, as indicated by lower levels of liver enzyme (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) compared to the control group. In terms of the lipid profile, the PRO-0.2 and PRO-0.5 groups had significantly lower serum levels of low-density lipoprotein, triglycerides, in linear and quadratic patterns, and cholesterol compared to the control group, with no significant differences in cholesterol levels. High-density lipoprotein increased significantly in both PRO-0.2 and PRO-0.5 groups after 90 days, following a linear pattern. Hepatic alkaline phosphatase levels decreased in both the PRO-0.2 and PRO-0.5 groups, following a significant linear pattern over time. After 30 days, the expression of hepatic fatty acid binding protein 3 (fabp3) significantly decreased in the PRO-0.5 group. Intestinal cluster of differentiation 36 (cd36) and fabp3 expression markedly increased, with cd36 showing the greatest rise. After 90 days, hepatic cd36 expression became prominent in both PRO-0.2 and PRO-0.5 groups. Expression of fas was significantly downregulated in both the PRO-0.2 and PRO-0.5 groups. Notably, hepatic lipoprotein lipase (lpl) expression significantly increased in the supplementation groups after 30 days but decreased significantly after 90 days. Overall, this study highlights the positive impact of dietary mixtures of Bacillus spp. on various aspects, including water quality, growth performance, feed utilization, survivability, expression of lipid metabolism-related genes, lipid profile, body composition, and bacterial load in both water and fish bodies.

Cost-effectiveness of Traditional Persian Medicine-Based Diet on NonAlcoholic Fatty Liver Disease

Background: In the context of Persian traditional medicine, there are several therapeutic strategies for managing diseases, ranging from lifestyle changes to herbal remedies.&#x0D; Objectives: Given the application of Persian traditional medicine in the management of chronic diseases, the burden of chronic illnesses, and the public’s recourse to traditional medicine specialists, this study aimed to assess the cost-effectiveness of traditional medicine dietary regimens for the treatment of non-alcoholic fatty liver disease from the perspective of the payer.&#x0D; Methods: In this study, we investigated the cost-effectiveness of providing nutrition counseling for lifestyle modification (changes in the aforementioned Setteh-e-Zarurieah) by a traditional medicine specialist compared to receiving counseling from a nutritionist for nonalcoholic fatty liver disease from the payer’s perspective. The outcomes measured were changes in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes, body mass index (BMI), and the grade of fatty liver. Cost and effectiveness data were entered into Excel software, and the ICER ratio was calculated&#x0D; Results: The results indicated that the dietary regimen prescribed by Persian traditional medicine when compared to the nutritionist’s recommended diet, resulted in a lower decrease in AST and ALT enzymes but led to a greater decrease in BMI (mean change = 0.42) and a significant change in the grade of fatty liver (OR = 9.75). Since the costs of tests, ultrasounds, and visits were equal in both groups, the cost difference was zero. In the first scenario, where traditional medicine is considered an alternative therapy and liver enzymes are the primary focus, providing nutritional counseling services by Persian traditional medicine may not be cost-effective. However, if we consider the grade of fatty liver and BMI as the primary variables, providing nutritional counseling services by Persian traditional medicine may be cost-effective.&#x0D; Conclusions: Based on the available evidence, the treatment of fatty liver using Persian traditional medicine can be considered an effective and cost-effective complementary (or alternative) intervention. Considering the long-term costs imposed by the health system and insurance organizations, it is predicted that adding visits to Persian traditional medicine specialists may reduce overall healthcare system costs.

Improved Bioavailability and Hepatoprotective Activity of Baicalein Via a Self-assembled Solutol HS15 Micelles System.

Baicalein (BA) is a flavonoid extract from the root of Scutellaria baicalensis Georgi with excellent biological activities, such as antioxidant and anti-inflammatory activities. However, its poor water solubility limits its further development. This study aims to prepare BA-loaded Solutol HS15 (HS15-BA) micelles, evaluate the bioavailability, and explore protective effects on carbon tetrachloride (CCl4) induced acute liver injury. The thin-film dispersion method was used to prepare HS15-BA micelles. The physicochemical, in vitro release, pharmacokinetics, and hepatoprotective effects of HS15-BA micelles were studied. The optimal formulation showed a spherical shape by characterization of the transmission electron microscope (TEM) with an average small size (12.50 nm). The pharmacokinetic results illustrated that HS15-BA increased the oral bioavailability of BA. The in vivo results showed that HS15-BA micelles significantly inhibited the activity of the CCl4-induced liver injury marker enzymes aspartate transaminase (AST) and alanine transaminase (ALT). Also, CCl4 induced oxidative damage to liver tissue, leading to increased L-glutathione (GSH) and superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) activity, while HS15-BA significantly reversed the above changes. Moreover, BA also had a hepatoprotective effect through anti-inflammatory activity; the results of ELISA and RT-PCR revealed that HS15-BA pretreatment significantly inhibited the increase in the expression of inflammatory factors induced by CCl4. In summary, our study confirmed that HS15-BA micelles enhanced the bioavailability of BA, and showed hepatoprotective effects through antioxidant and anti-inflammatory activities. HS15 could be considered a promising oral delivery carrier in treating liver disease.

Effect of hyperbaric oxygen treatment on patients with heatstroke complicated by multiple organ dysfunction:A retrospective study

BackgroundThe benefits of hyperbaric oxygen (HBO) in treating animals with heat stroke (HS) have been established. This study aims to retrospectively analyze the effect of HBO on multiple organ dysfunction following HS in humans. MethodsRetrospective data were collected from patients with HS admitted to our hospital in the past 7 years. Patients were categorized into groups based on whether they received HBO therapy. The study compared various factors, including sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation-Ⅱ (APACHE-Ⅱ) scores, mortality rates, neurological function scores, serum myocardial enzyme levels, liver, kidney, and coagulation function indicators, blood routine results, electrolyte levels, and modified Barthel index (MBI) score for standard daily living ability before treatment and after 2 and 4 weeks of treatment. ResultsThe mortality rates in the HBO and control group were 0% and 8.49%, respectively. Upon admission, the HBO group had higher SOFA and APACHE-Ⅱ scores and lower neurological, coagulation, and liver functions than those of the control group. HBO treatment significantly improved SOFA, APACHE-Ⅱ, and neurological scores while relieving levels of alanine aminotransferase, aspartate aminotransferase, creatinine, and myocardial enzymes. Additionally, it mitigating lymphocyte and platelet count decline caused by HS. The MBI score was significantly enhanced after treatment in the HBO group. ConclusionsClinical practice advocates administering HBO therapy to patients with severe illness, organ damage, and nerve impairment. Compared with conventional treatment, combined HBO therapy demonstrated superior efficacy in alleviating multiple organ dysfunction and improving daily living ability in patients with HS.

Ingestão proteica e perda de peso em indivíduos com sobrepeso ou obesidade

Introduction: Food plays a central role in weight loss. However, there is the possibility of maximizing health efficiency during this process, depending on the ingested amount of each macronutrient. Objective: To evaluate the effect of protein intake on weight loss in overweight and obese individuals. Material and Methods: A systematic review of the literature was carried out, according to the PRISMA methodology, using the PubMed, Scopus and Web of Science databases. Articles that met the inclusion criteria were selected, resulting in 14 eligible articles out of 422 initially identified. Results: Studies revealed that groups with higher protein intake had greater weight and fat loss - 4 (28.57%) and 6 studies (42.86%), respectively. It was also found that, associated with this weight loss, in 2 studies (14.29%) there were significant reductions in LDL cholesterol, and in 1 study (7.14%), there was a reduction in the levels of the enzymes aspartate aminotransferase and alanine aminotransferase. Effects on satiety and appetite were analyzed in 4 studies (28.57%), with 2 (14.29%) reporting higher levels of satiety and better appetite control in the higher protein intake group. Conclusion: A higher protein intake may enhance beneficial effects on weight loss in overweight or obese individuals, however there is a need for further studies to support the occurrences analyzed in this review.

Effects of combination of tramadol and sildenafil citrate (Viagra) on hepatic and renal function parameters in Male Albino Rats

Erectile dysfunction, premature ejaculation and pleasure seeking have increased the use of sildenafil citrate, tramadol and their combination by youths who believe these drugs could positively impact their sexual life. Sildenafil citrate and tramadol are metabolized in the liver, and their by-products excreted through the kidneys, making these organs possible targets for toxicity. Aim: This study evaluates the effects of combination of tramadol and sildenafil citrate on hepatic and renal function parameters in male albino rats. Methodology: A total of forty-nine (49) male albino rats weighing between 150 to 180g were used for the study. Sildenafil citrate and tramadol were administered to the rats by means of oral gavage for 28 days. The liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using the Reitman-Frankel method. Alkaline phosphatase (ALP) was determined using the Colorimetric endpoint method. Total protein (TP) was determined using the biuret method. Albumin (ALB) was determined using the bromocresol green method. Sodium (Na+), potassium (K+) and chloride (CL-) were determined using ion selective electrode (ISE) method. Bicarbonate (HCO3-) was determined using titrimetric method. Urea was determined using Urease bertholet method. Creatinine was determined using Jaffe-Slot method. Results: There were no significant differences (P&gt;.05) in the liver enzymes ALT, AST and ALP in all the treatment groups compared to the negative control. Total protein (TP) and albumin (ALB) also showed no significant differences (P&gt;.05) in the groups, compared to the negative control. there were no significant differences (P&gt;.05) in the electrolyte levels in the treatment groups, compared to the negative control. Urea and creatinine levels were also not significantly different (P&gt;.05) in the treatment groups, compared to the negative control. Conclusion: Administration of sildenafil citrate singularly and in combination with tramadol, at recommended and double doses for 28 days, did not impact the liver and was also non-toxic to the kidneys.

A Polyherbal Mixture with Nutraceutical Properties for Ruminants: A Meta-Analysis and Review of BioCholine Powder.

BioCholine Powder is a polyherbal feed additive composed of Achyrantes aspera, Trachyspermum ammi, Azadirachta indica, and Citrullus colocynthis. The objective of this study was to analyze published results that support the hypothesis that the polyherbal product BioCholine Powder has rumen bypass choline metabolites through a meta-analysis and effect size analysis (ES). Using Scopus, Web of Science, ScienceDirect, PubMed, and university dissertation databases, a systematic search was conducted for experiments published in scientific documents that evaluated the effects of BioCholine supplementation on the variables of interest. The analyzed data were extracted from twenty-one publications (fifteen scientific articles, three abstracts, and three graduate dissertations available in institutional libraries). The studies included lamb growing-finishing, lactating ewes and goats, calves, and dairy cows. The effects of BioCholine were analyzed using random effects statistical models to compare the weighted mean difference (WMD) between BioCholine-supplemented ruminants and controls (no BioCholine). Heterogeneity was explored, and three subgroup analyses were performed for doses [(4 (or 5 g/d), 8 (10 g/d)], supplementation in gestating and lactating ewes (pre- and postpartum supplementation), and blood metabolites by species and physiological state (lactating goats, calves, lambs, ewes). Supplementation with BioCholine in sheep increased the average daily lamb gain (p < 0.05), final body weight (p < 0.01), and daily milk yield (p < 0.05) without effects on intake or feed conversion. Milk yield was improved in small ruminants with BioCholine prepartum supplementation (p < 0.10). BioCholine supplementation decreased blood urea (p < 0.01) and increased levels of the liver enzymes alanine transaminase (ALT; p < 0.10) and albumin (p < 0.001). BioCholine doses over 8 g/d increased blood glucose, albumin (p < 0.10), cholesterol, total protein, and globulin (p < 0.05). The ES values of BioCholine in retained energy over the control in growing lambs were +7.15% NEm (p < 0.10) and +9.25% NEg (p < 0.10). In conclusion, adding BioCholine Powder to domestic ruminants' diets improves productive performance, blood metabolite indicators of protein metabolism, and liver health, showing its nutraceutical properties where phosphatidylcholine prevails as an alternative that can meet the choline requirements in ruminants.