Liver Enzymes Alanine Aminotransferase Research Articles

Behavioral, biochemical, immune, and histological responses of Nile tilapia (Oreochromis niloticus Linnaeus, 1758) to lead, mercury, and pendimethalin exposure: individual and combined effects

The aquaculture sector is facing environmental issues because of rising chemical pollution of aquatic systems, which may be caused by man-made or natural causes. The combined action of these mixtures can produce an effect that is either severalfold higher or severalfold lower than the overall toxicity of the individual components. The objective of this study is to evaluate the impact of three individual toxicants: lead (Pb 0.088 mg L−1), mercury (Hg 0.084 mg L−1), and pendimethalin (PM 0.355 mg L−1) and their combinations on the behavior, oxidative stress, immunology, biochemistry, and histopathological changes in Nile tilapia. The results show that mortality was evident across all treatment groups and was highest in the mixture (MIX) group, at 33.4%. Some of these behavioral changes included increased mucus secretion, fin rot, and dark skin coloration of the fish, all of which were evidently exacerbated in the MIX group. The erythrocyte and hemoglobin indices presented marked reductions in the MIX and PM groups in comparison to the control group. The MIX group had higher levels of serum creatinine and urea, as well as the liver enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. They also had higher levels of malondialdehyde and lower levels of total antioxidant capacity, which showed oxidative stress. The stress biomarkers, cortisol and glucose, showed greater impact on the MIX and PM groups. The neurobehavioral assessment demonstrated noticeable decreased acetylcholinesterase levels in PM and MIX-exposed groups. In the serum immunological parameters, levels of nitric oxide and lysozyme were lower, especially in the MIX and PM groups. In all experimental groups, especially the MIX group, the levels of spleen pro-inflammatory cytokine genes were higher. The histopathological examination revealed marked lesions in the gills, liver, and brains in the form of inflammation, necrosis, and circulatory alterations. Among the exposed groups, the MIX group exhibited the highest histopathological changes. Collectively, our findings demonstrated significant toxic effects of heavy metals and herbicides on Nile tilapia, revealing a synergistic impact on both physiological and histopathological responses resulting from combined exposures. The data evidently indicate the ecological hazards associated with heavy metals and herbicides in aquatic ecosystems.

High-Intensity Interval Training Reduces Liver Enzyme Levels and Improves MASLD-Related Biomarkers in Overweight/Obese Girls.

Despite the abundant body of evidence linking high-intensity interval training (HIIT) to cardiometabolic markers, little is known about how HIIT affects liver enzymes, particularly in obese adolescents. This study aimed to investigate the effects of HIIT on metabolic dysfunction-associated steatotic liver disease (MASLD)-related biomarkers in overweight/obese adolescent girls. Thirty-three overweight/obese adolescent girls (age, 17.0 ± 1.15 yr.; body mass index, 33.3 ± 4.77 kg/m2) were randomly assigned to HIIT (n = 17) or control (n = 16) groups. The HIIT group participated in a nine-week HIIT program (three times weekly) without caloric restriction. Maximal aerobic speed, body composition indexes, blood pressure, MASLD-related biomarkers [liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), plasma lipids, uric acid, platelet count, and homeostasis model assessment index for insulin-resistance (HOMA-IR)] were examined at baseline and after the intervention. Significant "time × group" interactions were found for body composition indexes, systolic blood pressure, maximal aerobic speed, liver enzymes ALT and AST, plasma lipids, glucose, and HOMA-IR. The HIIT program resulted in an increase in maximal aerobic speed (p = 0.035) and a decrease in body composition and plasma lipids (p < 0.01), systolic blood pressure (p = 0.011), ALT (p = 0.013), AST (p = 0.012), and HOMA-IR (p = 0.01), but no significant changes in uric acid and platelet count. None of these markers changed in the control group. HIIT resulted in an improvement in MASLD-related biomarkers. HIIT could be an effective exercise therapy to prevent and reverse MASLD in adolescents with obesity.

Investigating the Biological Impact of Melatonin on Male Albino Mice: A Comprehensive Characterization

Melatonin (Mel) is a chemical that has been found in bacterial, higher plants, invertebrates, and vertebrates. The plant extract was analyzed using high-performance liquid chromatography (HPLC) to find Mel. Mel concentrations differed greatly, according to the data. The aim of this study was to see how Mel generated from Ziziphus spina-christi leaves affected thyroid, liver enzymes, and lipid profiles in male albino mice. Twenty male mice were divided into four groups, each containing five mice, and were administered intraperitoneally (i.p) injections of Mel in three doses (4, 7 and 10 mg/ml), except for the control group, which received only a dose of normal saline solution. In comparison to the control therapy, the results showed that the Mel dose of 10 mg/ml had the greatest impact on lowering the levels of thyroid hormones (T3 and T4), lowering the levels of the liver enzymes Alanine transaminase (ALT), Aspartate aminotransferase (AST), and Total serum bilirubin (TSB) and lowering lipid profile (cholesterol (CHO), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides (TG)). In addition to raising the level of high-density lipoprotein (HDL) in mice's blood serum with substantial variations from the control therapy. The review summarizes, this evidence implicates Mel in a broad range of effects with a significant regulatory influence over many of the body's physiological functions. Keywords: Blood serum, Medicinal plants, tryptophan, Rhamnaceae family, methanol, TLC and pineal gland.

Enhanced safety and efficacy profile of CD40 antibody upon encapsulation in pHe-triggered membrane-adhesive nanoliposomes.

To develop pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL) of CD40a to enhance anti-tumor activity in pancreatic cancer while reducing systemic toxicity. A small library of nanoliposomes (NL) with various lipid compositions were synthesized to prepare pH (pHe)-triggered membrane adhesive nanoliposome (pHTANL). Physical and functional characterization of pHTANL-CD40a was performed via dynamic light scattering (DLS), Transmission Electron Microscopy (TEM), confocal microscopy, and flow cytometry. In vivo studies were performed using PDAC (Panc02) transplanted mice. Tumor tissue was analyzed by flow cytometry, and plasma cytokines and liver enzymes were analyzed by ELISA. pHTANL-CD40a reduced tumor growth, enhanced tumor immune infiltration/activation, and enhanced survival compared to vehicle and free-CD40a. Importantly, pHTANL-CD40a treatment resulted in significantly lower systemic toxicity as indicated by unchanged body weight, minimal organ deformity, and reduced serum levels of liver enzyme alanine transaminase (ALT) and inflammatory cytokine IL-6. pHTANL-CD40a is more effective than free CD40a in anti-tumor activity, especially in altering the TME immune landscape for a potential therapeutic benefit in combination with immunotherapy.

Evaluating the Hepatoprotective Potential of Ginger Ethanolic Extract Against Lambda-Cyhalothrin-Induced Toxicity in Male Rats

Ginger (Zingiber officinale Rosc.) is a traditional plant that is widely used as a spice or folk medicine. Lambda-cyhalothrin (LCT) is a synthetic pyrethroid that is widely used to control insecticide. The present study aimed to evaluate the potential protective effect of ginger ethanolic extract (GEE) on liver toxicity experimentally induced by LCT in albino rats. The experiment involved thirty adult male rats (‎Rattus norvegicus)‎, randomly ‎allocated to ‎one of three groups (n=10/group: control group, administered distilled water orally for 12 weeks‎; ‎LCT-treated group, received 5.43 mg/kg BW ‎(1/15 LD50‎ dose calculated in this study as 81.5 mg/kg BW) orally, for 12 weeks;‎ LCT-‎GEE-treated group, received the same dose of ‎LCT along with GEE at 100 mg/kg BW orally. Body weights were ‎recorded at the start, and at ‎‎4, 8, and 12 weeks into the treatment. Upon completion of the study, blood ‎samples were collected for liver ‎enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST)‎, ‎and alkaline phosphatase (ALP) ‎assessment. Additionally, liver samples were collected for histopathological‎ ‎examination‎.‎ The LCT-treated group exhibited a significant decrease in BW at 4, 8, and 12 weeks compared to the control ‎and LCT-GEE-treated groups. The LCT-treated rats showed increased levels of liver enzymes ALP, AST, and ‎ALT. Histological evaluation revealed signs of liver necrosis, mononuclear cell infiltration, and congestion in ‎LCT-treated rats. These pathological changes were less pronounced in the LCT-GEE-treated group, indicating ‎a mitigating effect. The study demonstrates the detrimental effects of LCT on the health of male rats, ‎particularly regarding BW and liver health. Alongside, it highlights Zingiber officinale's potential in reducing ‎these adverse effects, suggesting its efficacy in environments with LCT exposure‎‎‎.

Zinc pretreatment for protection against intestinal ischemia-reperfusion injury.

Intestinal ischemia-reperfusion (I/R) injury (II/RI) is a critical condition that results in oxidative stress, inflammation, and damage to multiple organs. Zinc, an essential trace element, offers protective benefits in several tissues during I/R injury, but its effects on intestinal II/RI remain unclear. To investigate the effects of zinc pretreatment on II/RI and associated multiorgan damage. C57BL/6 mice were pretreated with zinc sulfate (ZnSO4, 10 mg/kg) daily for three days before I/R injury was induced via superior mesenteric artery occlusion (SMAO) and abdominal aortic occlusion (AAO) models. Tissue and serum samples were collected to evaluate intestinal, liver, and kidney damage using Chiu's score, Suzuki score, and histopathological analysis. Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species (ROS) and superoxide dismutase (SOD) levels. Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models (P < 0.001). The serum levels of liver enzymes (alanine aminotransferase, aspartate aminotransferase) and kidney markers (creatinine and urea) were lower in the zinc-treated mice than in the control mice, indicating reduced hepatic and renal injury. In vitro, zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury. Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls. Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage. These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.

Biochemical Studies of Averrhoa carambola Ethanol Leaf and Fruit Extracts on Alloxan-induced Diabetic Rats

The use of herbal medicines has always been an option to treat diseases such as diabetes cancer and other ailments. This study aimed to evaluate the effect of Averrhoa carambola leaf and its fruit ethanol extracts on biochemical parameters and histopathology features. Forty five albino rats were assigned into 9 groups of 5 rats each. Except for the normal control group, others were induced to be diabetic by a single intraperitoneal injection of alloxan. Group 1 (normal control) and Group 2 (diabetic untreated) received water. Group 3 received 2.5mg/kg glibenclamide, Groups 4-9 received graded doses (250mg/kg, 500mg/kg and 750mg/kg) of leaf and fruit extracts of Averrhoa carambola. Treatment lasted 14days. At the end of the treatment, blood samples and organ (pancreas) were collected from the animals for biochemical and histopathological evaluation. Treatment of alloxan-induced diabetic rats significantly (p&lt;0.05) reduced the glucose concentration across all treated groups. Following induction of diabetic mellitus, the serum activities of liver enzymes (Alanine amino transferase, Aspartate aminotransferase and Alkaline phosphatase), low-density lipoprotein cholesterol (LDL-C) and triglyceride were significantly (p&lt;0.05) elevated in diabetic untreated group with corresponding reduction in serum protein, albumin and high-density lipoprotein cholesterol (HDL-C) compared to the normal control and treated groups. However, the fruit extracts exhibited a high increase in urea and creatinine levels especially at dose of 750mg/kg body weight when compared with the leaf though not significantly higher than the diabetic untreated group. From histopathology studies, the groups treated with the leaf extract of Averrhoa carambola showed greater structural improvement and an increase in pancreatic islet cells. Therefore this study showed that although ethanol extracts of Averrhoa carambola leaf and fruit have antidiabetic properties, the leaf extract possesses more antidiabetic effect.

Investigation of hematological, biochemical and coagulological markers, their diagnostic effectiveness in toxic hepatitis in patients with COVID‑19

This article discusses hematological, biochemical and coagulological markers for the diagnosis of toxic hepatitis in patients with COVID-19. The analysis of the effectiveness of these markers in a large sample of patients confirmed their importance for the early detection of toxic hepatitis b in patients with COVID-19. Blood parameters such as platelets, ALT, AST, bilirubin, as well as coagulograms and markers of protein metabolism (albumin) conducted among patients divided into control and experimental groups were analyzed. It was found that in patients with concomitant toxic hepatitis c COVID-19, the tendency of thrombocytopenia is most common in clinical blood analysis. Among the biochemical parameters of blood, liver markers increase (ALT, GGT, alkaline phosphatase, etc.). It should be noted that in 1/3 of patients, the activity of liver enzymes alanine aminotransferase and aspartate aminotransferase increases, which indicates a violation of liver function.The analysis of these data using ROC analysis showed high diagnostic accuracy of these markers in the detection of toxic hepatitis in patients with COVID-19. These studies may be important for more effective screening and further monitoring of appropriately selected treatment in such clinical situations and contributes to more effective management of this condition, leading to an improved prognosis of this disease. This study is important in the context of understanding the effects of COVID-19 on liver function.

Hepatoprotective Effect of L-Carnitine is Achieved via Activating Nrf2 and Targeting TLR4 Signaling Pathways in Thioacetamide – Induced Liver Fibrosis in Rats

Background: Liver fibrosis is a critical health problem that can result in serious illness and death. L-carnitine (LC) is a naturally occurring compound which transports fatty acids through the inner mitochondrial membrane for consequent beta-oxidation. It acts as an antioxidant to lessen cellular oxidative stress. Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. This study was carried out to investigate the hepatoprotective effects of LC via modulation of Nrf2 signaling and TLR4 targeting pathways in rats with liver fibrosis induced by Thioacetamide (TAA). Methods: Twenty-four adult male Wister rats were assigned into four groups as follows: Group 1 served as a normal non- treated control. Rats in group 2 were injected intraperitoneally (IP) with Thioacetamide (TAA) twice a week at a dose of 200 mg/kg B.wt for 6 weeks to produce liver fibrosis. Two weeks following TAA injections, 50 and 100 mg/kg of LC were administered to the rats in groups 3 and 4, respectively concurrently with TAA injections until end of the experiment (6 weeks). Results: Intraperitoneal injection of LC decreased the levels of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats with liver fibrosis induced by TAA. Malondialdehyde (MDA), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and toll-like receptor 4 (TLR4) levels were significantly decreased in LC treated groups. LC injection increased albumin, superoxide dismutase (SOD), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione (GSH) levels. Additionally, expression of Phosphoinositide 3-kinase (PI3K) was increased and expression of TLR4 was decreased in LC treated groups according to PCR data. The biochemical findings were supported by histopathological findings. Regarding immunohistopathological examination, the LC treated groups reduced hepatic expression of caspase-3 an

Epicatechin ameliorates glucose intolerance and hepatotoxicity in sodium arsenite-treated mice

Arsenic is a metalloid found in the environment that causes toxic effects in different organs, mainly the liver. This study aimed to investigate the protective effects of epicatechin (EC), a natural flavonol, on glucose intolerance (GI) and liver toxicity caused by sodium arsenite (SA) in mice. Our findings showed that SA exposure led to the development of GI. Liver tissue damage and decreased pancreatic Langerhans islet size were also observed in this study. Mice exposed to SA exhibited hepatic oxidative damage, indicated by reduced antioxidant markers (such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione), along with elevated levels of thiobarbituric acid reactive substances. SA administration elevated the serum activities of liver enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Furthermore, notable increases in the levels of inflammatory and apoptotic markers (Toll-like receptor 4, nuclear factor-kappa B, tumor necrosis factor-α, nitric oxide, B-cell lymphoma-2, and cysteine aspartate-specific protease-3) were observed in the liver. Treatment of SA-exposed mice with EC considerably reversed these biochemical and histological changes. This study demonstrated the beneficial effects of EC in ameliorating SA-induced hyperglycemia and hepatotoxicity due to its ability to enhance the antioxidant system by modulating inflammation and apoptosis.

Retrospective Study on the Features and Outcomes of a Tuscany COVID-19 Hospitalized Patients Cohort: Preliminary Results.

Background: A few months after the COVID-19 pandemic onset, knowledge of SARS-CoV-2 infection and outcomes and treatments blew up. This paper aimed to evaluate the features of a Tuscany COVID-19 hospitalized cohort and to identify risk factors for COVID-19 severity. Methods: This retrospective observational COVID-19 cohort study (1 March 2020-1 March 2021) was conducted on patients ≥ 18 years old, admitted to Tuscany Hospital, and subjected to follow-up within 12 months after discharge. Patients were enrolled at Pisana, Senese and Careggi University Hospitals, and South East, North West, and Center Local Hospitals. Results: 2888 patients (M = 58.5%, mean age = 66.2 years) were enrolled, of whom 14.3% (N = 413) were admitted to an intensive care unit. Smokers were 25%, and overweight and obese 65%. The most used drugs were corticosteroids, antacids, antibiotics, and antithrombotics, all antiviral drugs, with slight differences between 2020 and 2021. A strong association was found between outcomes of evolution towards critical COVID-19 (non-invasive mechanical ventilation (NIV) and/or admission to intensive care) and smoking (RR = 4.91), ex-smoking (RR = 3.48), overweight (RR = 1.30), obese subjects (RR = 1.62), comorbidities (aRR = 1.38). The alteration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyl transpeptidase) was associated with NIV (aOR = 2.28). Conclusions: Our cohort, characterized by patients with a mean age of 66.2 years, showed 65% of patients were overweight and obese. Smoking/ex-smoking, overweight/obesity, and other comorbidities were associated with COVID-19 adverse outcomes. The findings also demonstrated that alterations in liver enzymes were associated with worse outcomes.

Non-linear association of liver enzymes with cognitive performance in the elderly: A cross-sectional study.

Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance. In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects. The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L. There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.

Pharmacological benefits of durva swaras (Cynodon dactylon L. Pers.) administration in APAP-induced liver injury model of mice - Assessment by metabolic and inflammatory markers.

Liver derangement underlies the development of metabolic syndrome in perimenopause. Previously, we have observed that durva swaras (DS) improved metabolic-associated fatty liver disease (MAFLD) and abnormal liver enzymes (aspartate aminotransferase and alanine aminotransferase) along with other complications of menopause in ovariectomized rats. We aimed to decipher the hepatoprotective mechanisms of DS in acetaminophen (APAP)-induced liver injury model, which is analogous to the pathophysiology of MAFLD. Male Swiss albino mice were distributed into three groups at random. Group I (Control) was administered with vehicle (distilled water) for 7 days. Group II (APAP) received vehicle for the first 6 days and APAP (350 mg/kg - single dose) on the 7th day. Group III (APAP + D) received test compound DS (quality complied) at a dose of 133 mg/kg for 6 days and APAP (350 mg/kg - single dose) on the 7th day. Subsequently, blood and liver tissues were subjected to biochemical, ultrastructural, and gene expression analysis. DS pretreatment protected the liver from APAP-induced disruption of sinusoids and necrosis. DS prevented the elevation of liver enzymes - AST and ALT induced by APAP. Importantly, DS inhibited the APAP-elicited increase in messenger ribonucleic acid levels of hepatic nuclear factor-kappa beta (NF-κB) and pro-inflammatory cytokines, namely interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha. Moreover, DS activated gene expression of nuclear factor erythroid 2-related factor 2 and liver-X-receptor-alpha (LXR-α) to combat the liver damage. DS hinders APAP-induced liver damage by activating LXR-α and inhibiting the NF-κB-associated pro-inflammatory cytokine gene expression. These observations confirm the protective role of DS in metabolic dysfunction-associated liver conditions.

Association Between Serum Ferritin Level and Liver Function Tests in Children with Beta-Thalassemia (Thalassemia Center of Kut Hospital, Iraq)

Background: Thalassemia represents a heterogeneous autosomal recessive hereditary anemia.Ferritin is a 450 KDa soluble protein. It can be found in all of the body's cells, but it's particularly abundant in marrow macrophages, spleen, and liver.Objective: In patients with β thalassemia major and β thalassemia Intermedia, serum ferritin levels are measured, and their correlation with bilirubin levels, liver enzymes AST (aspartate transaminase) and ALT (alanine transaminase), in beta-thalassemia major and β thalassemia Intermedia.Patients and Methods: A cross-section study that involved 90 patientsincluded 50 Thalassemia Major (TM) and 40 Thalassemia intermediate(TI). Patients who were randomly chosen for this study would be gathered from the Kut Hospital Thalassemia Center. Every patient's are kid, aged 5 to 17, regardless of gender. Abbott C4000 Architect Additionally, the TSB, ALT, AST, and serum ferritin were determined using the Cobas c 111 analyzer.Results: The studies include both genders 52.9% of the females had B-thalassemia major and 47.1% had β-thalassemia intermediate, whereas 57.1% of the men had βTM and 42.9% had βTI. There were 37.8% of females and 62.2% of males in the sample.Patients with severe thalassemia exhibited a statistically significant increase in the mean± SD of serum ferritin (4016.54 ± 2500.81 ng/ml) compared to the mean ± SD of β-thalassemia intermedia (1629.48 ± 1235.33 ng/ml), with a p-value of 0.000. Patients with major β-thalassemia had a mean TSB level that was statistically significantly lower (1.32 ± 0.69 mg/dl) than the mean level of β-thalassemia intermedia (2.10 ± 0.86 mg/dl), with a p-value of 0.000. In the B-thalassemia major group, serum hepcidin did not exhibit a statistically significant association with serum ferritin (r=-0.04), while in the B-thalassemia intermedia group, serum ferritin exhibited a statistically significant moderate negative correlation with TSB (r=-0.38), p-value. 0.01.Conclusions: Ferritin levels may be useful in thalassemia syndrome diagnosis and prognosis determination.

Antibacterial activity against multidrug-resistant Salmonella, toxicity and biochemical effects of Moringa oleifera leaf extracts in mice

Abstract. Ngemenya MN, Itoe LO, Awah LA, Asongana R, Ndip RA. 2024. Antibacterial activity against multidrug-resistant Salmonella, toxicity and biochemical effects of Moringa oleifera leaf extracts in mice. Asian J Nat Prod Biochem 22: 43-50. The emergence of multidrug resistance has significantly compromised the treatment of Salmonella infections. The anti-Salmonella activity, toxicity, and biochemical effects of Moringa oleifera Lam. leaf crude extracts were studied by disc diffusion and microdilution against Multidrug-Resistant (MDR) strains. Cytotoxicity was investigated on monkey kidney epithelial cells (LLCMK2) and acute toxicity in BALB/c mice. Both hexane (MOHEX) and methanol (MOMET) extracts produced small zones of inhibition of 8mm at 1 mg and 2 mg per disc, indicating weak activity, but the minimum inhibitory concentration showed high (0.0625 mg/mL) to low activity (10 mg/mL) activity. No minimum bactericidal concentration was recorded at the concentrations tested. The 50% cytotoxic concentration (CC50) for methanol and hexane extracts were 2524 µg/mL and 5004 µg/mL, respectively, indicating a low risk of toxicity. No mortality or adverse effects were recorded in the acute toxicity test. Both extracts had no significant effects (p &lt; 0.05) on renal function and one liver enzyme (alanine aminotransferase), but MOMET significantly increased aspartate aminotransferase (p = 0.04), suggesting possible liver toxicity. The study shows that M. oleifera leaves possess bacteriostatic activity against multidrug-resistant Salmonella and are non-toxic; hence, it is a potential alternative treatment against multidrug-resistant Salmonella. Further studies of fractions and pure natural products of the extracts should be pursued.

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.

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&lt;0.001, but the ALP has no significant differences P&gt;0.05. In Study group 2, (HIV/AIDS patients on ART) showed significant differences of P&lt;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

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.

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.