ABSTRACT
The study was planned to evaluate the differences in certain proinflammatory cytokines(IL-6, TNF-α) with CRP and biochemical parameters (E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid), between women with pre- and postmenopausal breast cancer and seemingly healthy women in Iraqi women as controls; at medical city in teaching Oncology hospital,70 breast cancer patients women their ages ranged (47.51 ± 1.18) and 20 healthy women with age (44.45 ± 2.66) begun from September (2020) to February (2021). The aims of this study to investigate the evaluation of chemotherapy effects especially doxorubicin and cyclophosphamide only use in this study in pre and postmenopausal breast cancer women on proinflammatory cytokines(IL-6, TNF-α) with CRP and on biochemical parameters(E2, D3, LDH, GGT, TSB, Ca, Ph, uric acid) in pre and postmenapausal breast cancer women. The patients were divided into five groups and each group contains 14 patients women with breast cancer during pre and postmenopausal periods. The control groups were divided into 10 pre and 10 postmenopausal women(Fig. 1). The results of proinflammatory cytokines of and biochemical parameters in premenopausal groups were as the levels of IL-6 (pg/ml),TNF-α(pg/ml) and CRP (ng/ml) showed significant increase differences (P < 0.01)among breast cancer treated (BCT) groups in comparison with control groups,While the Liver enzymes GGT,LDH and TSB showed highly significant increase (P < 0.01) in BCT groups, Estrogen levels (pg/ml) and D3(ng/ml) increased significantly (P < 0.01)among BCT groups. Blood serum calcium and phosphorus with uric acid levels (mg/dl) showed significant difference (P < 0.01); While the result in postmenopausal of IL-6(pg/ml), TNF-α (pg/ml) and CRP (ng/ml) showed highly significant differences (P < 0.01)among BCT groups.While GGT(IU/L), LDH(IU/L) and TSB (mg/dl) enzymes were increased significantly (p < 0.01), Estrogen (pg/ml) and D3(ng/ml) levels showed significant increase (P < 0.01) among BCT groups.Blood calcium and phosphorus showed significant increase (P < 0.01) while uric acid was non-significant increase (P > 0.05).
Subject(s)
Breast Neoplasms , Cytokines , Postmenopause , Humans , Female , Breast Neoplasms/blood , Postmenopause/blood , Middle Aged , Cytokines/blood , Adult , Premenopause/blood , Tumor Necrosis Factor-alpha/blood , Interleukin-6/blood , C-Reactive Protein/metabolism , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic useABSTRACT
AIMS: Previous studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors. METHODS: This prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid-pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back-propagation artificial neural network was performed to rank independently risk factors of GDM. RESULTS: Women diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all p < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (ORs) ranging from 2.76 to 8.11 (all p < 0.05). Moreover, the ORs of GDM increased linearly with liver enzymes level (all P for overall association <0.001). Furthermore, Back-propagation artificial neural network identified γ-gamma-glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%). CONCLUSIONS: Single or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.
Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Diabetes, Gestational/epidemiology , Pregnancy Trimester, First , Prospective Studies , Risk Factors , LiverABSTRACT
BACKGROUND: Intravascular inflammation and an antiangiogenic state have been implicated in the pathophysiology of preeclampsia. On the basis of the profiles of their angiogenic/antiangiogenic factors, women with preeclampsia at term may be classified into 2 subgroups with different characteristics and prevalence of adverse outcomes. This study was undertaken to examine whether these 2 subgroups of preeclampsia at term also show differences in their profiles of intravascular inflammation. OBJECTIVE: This study aimed to determine the plasma profiles of cytokines and chemokines in women with preeclampsia at term who had a normal or an abnormal angiogenic profile. STUDY DESIGN: A nested case-control study was conducted to include women classified into 3 groups: women with an uncomplicated pregnancy (n=213) and women with preeclampsia at term with a normal (n=55) or an abnormal (n=41) angiogenic profile. An abnormal angiogenic profile was defined as a plasma ratio of placental growth factor and soluble fms-like tyrosine kinase-1 multiple of the median <10th percentile for gestational age. Concentrations of cytokines were measured by multiplex immunoassays. RESULTS: Women with preeclampsia at term and an abnormal angiogenic profile showed evidence of the greatest intravascular inflammation among the study groups. These women had higher plasma concentrations of 5 cytokines (interleukin-6, interleukin-8, interleukin-12/interleukin-23p40, interleukin-15, and interleukin-16) and 7 chemokines (eotaxin, eotaxin-3, interferon-γ inducible protein-10, monocyte chemotactic protein-4, macrophage inflammatory protein-1ß, macrophage-derived chemokine, and thymus and activation-regulated chemokine compared to women with an uncomplicated pregnancy. By contrast, women with preeclampsia at term and a normal angiogenic profile, compared to women with an uncomplicated pregnancy, had only a higher plasma concentration of monocyte chemotactic protein-4. A correlation between severity of the antiangiogenic state, blood pressure, and plasma concentrations of a subset of cytokines was observed. CONCLUSION: Term preeclampsia can be classified into 2 clusters. One is characterized by an antiangiogenic state coupled with an excessive inflammatory process, whereas the other has neither of these features. These findings further support the heterogeneity of preeclampsia at term and may explain the distinct clinical outcomes.
Subject(s)
Pre-Eclampsia , Pregnancy , Female , Humans , Placenta Growth Factor , Cytokines , Case-Control Studies , Angiogenesis Inducing Agents , Biomarkers , Inflammation , Monocyte Chemoattractant Proteins , Vascular Endothelial Growth Factor Receptor-1ABSTRACT
Liver injury with marked elevation of aspartate aminotransferase enzyme (AST) is commonly observed in dengue infection. To understand the pathogenesis of this liver damage, we compared the plasma levels of hepatic specific, centrilobular predominant enzymes (glutamate dehydrogenase, GLDH; glutathione S transferase-α, αGST), periportal enriched 4-hydroxyphenylpyruvate dioxygenase (HPPD), periportal predominant arginase-1 (ARG-1), and other non-specific biomarkers (paraoxonase-1, PON-1) in patients with different outcomes of dengue infection. This hospital-based study enrolled 87 adult dengue patients, stratified into three groups based on plasma AST levels (< 80, 80-400, > 400 U/L) in a 1:1:1 ratio (n = 40, n = 40, n = 40, respectively. The new liver enzymes in the blood samples from the 4th to 6th days of their illness were measured by commercial enzyme-linked immunosorbent assay (ELISA) or colorimetric kits. Based on the diagnosis at discharge days, our patients were classified as 40 (46%) dengue without warning signs (D), 35 (40.2%) dengue with warning signs (DWS), and 11 (12.6%) severe dengue (SD) with either shock (two patients) or AST level over 1000 U/L (nine patients), using the 2009 WHO classification. The group of high AST (> 400 U/L) also had higher ALT, GLDH, ARG-1, and HPPD than the other groups, while the high (> 400 U/L) and moderate (80-400 U/L) AST groups had higher ALT, αGST, ARG-1, and HPPD than the low AST group (< 80 U/L). There was a good correlation between AST, alanine aminotransferase enzyme (ALT), and the new liver biomarkers such as GLDH, αGST, ARG-1, and HPPD. Our findings suggest that dengue-induced liver damage initiates predominantly in the centrilobular area toward the portal area during the dengue progression. Moreover, these new biomarkers should be investigated further to explain the pathogenesis of dengue and to validate their prognostic utility.
Subject(s)
Aspartate Aminotransferases , Biomarkers , Dengue , Liver , Humans , Male , Biomarkers/blood , Female , Adult , Dengue/blood , Dengue/diagnosis , Dengue/complications , Case-Control Studies , Middle Aged , Aspartate Aminotransferases/blood , Vietnam , Liver/pathology , Young Adult , Liver Diseases/blood , Glutathione Transferase/blood , Aged , Southeast Asian PeopleABSTRACT
BACKGROUND: Pollution with heavy metals (HMs) is time- and concentration-dependent. Lead and zinc pollute the aquatic environment, causing severe health issues in aquatic animals. MATERIALS AND METHODS: Nile tilapia, the predominant cultured fish in Egypt, were experimentally exposed to 10% of LC50 of lead nitrate (PbNO3) and zinc sulfate (ZnSO4). Samples were collected in three different periods, 4, 6, and 8 weeks, in addition to a trial to treat the experimental fish infected with Aeromonas hydrophila, with an antibiotic (florfenicol). RESULTS: Liver enzymes were linearly upsurged in a time-dependent manner in response to HMs exposure. ALT was 92.1 IU/l and AST was 82.53 IU/l after eight weeks. In the eighth week of the HMs exposure, in the hepatic tissue, the levels of glutathione peroxidase (GPx), catalase (CAT), and metallothionein (MT) were increased to 117.8 U/mg prot, 72.2 U/mg prot, and 154.5 U/mg prot, respectively. On exposure to HMs, gene expressions of some cytokines were linearly downregulated in a time-dependent manner compared to the control. After four weeks of exposure to the HMs, the oxidative burst activity (OBA) of immune cells was decreased compared to the control 9.33 and 10.3 cells, respectively. Meanwhile, the serum bactericidal activity (SBA) significantly declined to 18.5% compared to the control 32.6% after eight weeks of exposure. Clinical signs of A. hydrophila infection were exaggerated in polluted fish, with a mortality rate (MR) of 100%. The re-isolation rate of A. hydrophila was decreased in fish treated with florfenicol regardless of the pollution impacts after eight weeks of HMs exposure. CONCLUSION: It could be concluded that the immune suppression and oxidative stress resulting from exposure to HMs are time-dependent. Clinical signs and post-mortem lesions in polluted fish infected with A. hydrophila were prominent. Infected-Nile tilapia had weak responses to florfenicol treatment due to HMs exposure.
Subject(s)
Cichlids , Lead , Animals , Lead/toxicity , Zinc Sulfate , Nitrates , Aeromonas hydrophilaABSTRACT
PURPOSE: Recent evidence suggests that adherence to dietary approaches to stop hypertension (DASH) diet can be effective in managing non-alcoholic fatty liver disease (NAFLD). We investigated the effect of DASH diet on hepatic fibrosis, steatosis and liver enzymes in patients with NAFLD. METHODS: This 12-week randomized controlled trial was conducted among seventy patients with NAFLD who were randomly assigned into two groups including intervention group (DASH diet containing 50-55% carbohydrate, 15-20% protein, and 30% total fat) and the control group (a healthy diet containing 50-55% carbohydrate, 15-20% protein, and 30% total fat). Both diets were calorie-restricted (500-700 kcal lower than the energy requirement). The primary outcomes included hepatic fibrosis, hepatic steatosis, alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT). RESULTS: At the baseline, there was no significant difference between two groups in the level of hepatic fibrosis (P = 0.63), hepatic steatosis (P = 0.53), ALT (P = 0.93), AST (P = 0.18) and GGT (P = 0.76). A significant reduction was found in the intervention group compared to the control group in hepatic fibrosis (23 grades reduction vs. 7 grades reduction; P = 0.008) and hepatic steatosis (31 grades reduction vs. 9 grades reduction; P = 0.03) after intervention. In addition, a significant change was observed in the intervention group compared to control group in ALT ( - 8.50 ± 8.98 vs. - 2.09 ± 7.29; P = 0.002), and AST ( - 5.79 ± 6.83 vs. - 0.51 ± 6.62; P = 0.002). CONCLUSIONS: Adherence to DASH diet may be effective in management of NAFLD. TRIAL REGISTRATION: The trial was registered on 06 February 2022 at Iranian Registry of Clinical Trials (IRCT20170117032026N3) with URL: https://www.irct.ir/trial/60887 .
Subject(s)
Dietary Approaches To Stop Hypertension , Non-alcoholic Fatty Liver Disease , Humans , Iran , Liver Cirrhosis , Diet , gamma-Glutamyltransferase , Alanine Transaminase , Aspartate Aminotransferases , Liver/pathology , CarbohydratesABSTRACT
The broad spectrum of hepatobiliary involvement in cystic fibrosis (CF) has been commonly referred to as cystic fibrosis liver disease (CFLD). However, differences in the definitions of CFLD have led to variations in reported prevalence, incidence rates, and standardized recommendations for diagnosis and therapies. Harmonizing the description of the spectrum of hepatobiliary involvement in all people with CF (pwCF) is deemed essential for providing a reliable account of the natural history, which in turn supports the development of meaningful clinical outcomes in patient care and research. Recognizing this necessity, The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) commissioned and tasked a committee to develop and propose a systematic classification of the CF hepatobiliary manifestations to increase uniformity, accuracy, and comparability for clinical, registry, and research purposes. This report describes the committee's combined expert position statement on hepatobiliary involvement in CF, which has been endorsed by NASPGHAN and ESPGHAN. We recommend using CFHBI (Cystic Fibrosis Hepato-Biliary Involvement) as the updated term to describe and classify all hepatobiliary manifestations in all pwCF. CFHBI encompasses the current extensive spectrum of phenotypical, clinical, or diagnostic expressions of liver involvement observed in pwCF. We present a schematic categorization of CFHBI, which may also be used to track and classify the changes and development of CFHBI in pwCF over time. The proposed classification for CFHBI is based on expert consensus and has not been validated for clinical practice and research purposes. Achieving validation should be an important aim for future research.
Subject(s)
Cystic Fibrosis , Elasticity Imaging Techniques , Gastroenterology , Liver Diseases , Child , Humans , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Liver Diseases/diagnosis , Platelet CountABSTRACT
Diabetic nephropathy, a common complication of type 2 diabetes (T2DM), is associated with abnormal lipid profiles, liver dysfunction, and kidney impairment. However, research on its association with trace elements in Iraqi patients is limited. The objective of the present study is to evaluate the association between lipid profile, liver function, and trace elements in diabetic nephropathy (DN) patients. In this study, 120 individuals were selected. Sixty of these individuals were labeled as the DN patient group, and 60 individuals were labeled as the healthy control group. A flame atomic absorption spectrophotometer (FAAS) was utilized to assess the levels of zinc (Zn), copper (Cu), and magnesium (Mg), whereas a flameless atomic absorption (FAA) was used to assess manganese (Mn). A colorimetric method was used based on the protocols included in the leaflets by Spinreact kits to determine the levels of lipid profiles and liver function enzymes in the serum. The mean value of high-density lipoprotein (HDL) decreased significantly in the DN patient group compared to the control group (p < 0.001) while cholesterol and low-density lipoprotein (LDL) decreased insignificantly. Conversely, the mean value of triglycerides (TGs) increased significantly in patient group ((p < 0.001) while very low-density lipoprotein (VLDL) increased insignificantly. On the other hand, the mean values of aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), and γ- glutamyl transferase (GGT) were significantly greater in DN patients compared to the healthy controls. Conversely, the mean values of total protein (TP) and albumin (Alb) were significantly lower in the DN patient group. In terms of trace elements, the mean values of Zn, Mg, and Mn were significantly lower in each of the patient groups compared to the healthy group. Conversely, a significant elevation in the means of Cu and Fe was observed in patients compared to the healthy group. Additionally, the findings revealed no association between BMI and lipid profile, liver enzymes, or trace elements. However, an association with age was limited to TGs, ALP, and GGT. The study's results show that the DN patients have abnormalities in their serum trace element levels. This means that these elements could be valuable indicators for monitoring and assessing the progression of DN. Understanding the correlation between lipid profile, liver function, and trace elements could offer valuable insights for managing and preventing diabetic nephropathy. More extensive studies, including an additional group of DM patients without nephropathy complications, are required, and could be used in practice due to the progression of the disease.
ABSTRACT
BACKGROUND: The incidence of hypertension (HTN) as a worldwide health problem is rising rapidly. Early identification and management of pre-HTN before HTN development can help reduce its related complications. We evaluated the relationship between liver enzymes levels and pre-HTN/HTN in the Azar cohort population. METHOD: This cross-sectional study was based on data from the large Azar cohort study and a total of 14,184 participants were included. Pre-HTN and HTN were defined based on the American Heart Association guideline. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) levels were measured by Pars Azmoon kits. The relationship between pre-HTN/HTN and liver enzyme levels was evaluated by logistic regression. RESULTS: Of 14,184 participants, 5.7% and 39.6% had pre-HTN and HTN, respectively. In the adjusted model, AST levels of 19-23 IU/l were associated with an elevated risk of pre-HTN (OR [95% CI]: 1.24 [1.04-1.48]). A dose-response increase was seen in pre-HTN in relation to ALT, with the highest OR in the third tertile (1.34 [1.09-1.63]). The odds of pre-HTN also increased with GGT in the third tertile (1.25[1.03-1.52]). In addition, the odds of HTN increased with increased levels of AST, ALT, ALP, and GGT, such that the highest ORs were recorded in the third tertile (OR 1.22 [1.09-1.37], 1.51 [1.35-1.70], 1.19 [1.07-1.34], and 1.68 [1.49-1.89], respectively). Among these enzymes, GGT had the highest OR regarding HTN. CONCLUSION: This study indicates that AST, ALT, ALP and GGT levels were associated with pre-HTN (except for ALP) and HTN, independent of known risk factors. Hence, it may be possible to use liver enzymes to predict the incidence of pre-HTN and HTN, empowering primary care providers to make the necessary interventions promptly.
Subject(s)
Alanine Transaminase , Alkaline Phosphatase , Aspartate Aminotransferases , Biomarkers , Blood Pressure , Hypertension , Liver , Prehypertension , gamma-Glutamyltransferase , Humans , Male , Hypertension/epidemiology , Hypertension/diagnosis , Hypertension/enzymology , Hypertension/blood , Female , Cross-Sectional Studies , Middle Aged , Alanine Transaminase/blood , gamma-Glutamyltransferase/blood , Biomarkers/blood , Alkaline Phosphatase/blood , Risk Factors , Adult , Aspartate Aminotransferases/blood , Liver/enzymology , Risk Assessment , Prehypertension/enzymology , Prehypertension/epidemiology , Prehypertension/diagnosis , Prehypertension/blood , Prehypertension/physiopathology , Clinical Enzyme Tests , Incidence , Predictive Value of TestsABSTRACT
Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4-6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7-9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p < .01) and behavioral responses (frequencies of jumping, frequencies of two-legged standing, Straub tail reaction) (p < .01) were significantly observed in the groups receiving TSE and Thymol (Groups 4-9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p < .01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p < .01). Groups 5-9 were significantly different from Group 2 in terms of malondialdehyde levels (p < .01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans.
Subject(s)
Antioxidants , Liver , Morphine , Plant Extracts , Substance Withdrawal Syndrome , Thymol , Animals , Substance Withdrawal Syndrome/drug therapy , Substance Withdrawal Syndrome/metabolism , Mice , Plant Extracts/pharmacology , Plant Extracts/chemistry , Thymol/pharmacology , Thymol/therapeutic use , Antioxidants/pharmacology , Liver/drug effects , Liver/metabolism , Morphine/pharmacology , Male , Behavior, Animal/drug effects , Clonidine/pharmacology , Clonidine/therapeutic use , Lamiaceae/chemistry , Nitric Oxide/metabolismABSTRACT
PURPOSE: This study aimed to examine the potential benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetes mellitus (DM) using a real-world database. METHODS: We analyzed individuals with MAFLD and DM newly initiated on SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors from a large-scale administrative claims database. The primary outcome was the change in the fatty liver index (FLI) assessed using a linear mixed-effects model from the initiation of SGLT2 or DPP4 inhibitors. A propensity score-matching algorithm was used to compare the change in FLI among SGLT2 and DPP4 inhibitors. RESULTS: After propensity score matching, 6547 well-balanced pairs of SGLT2 and 6547 DPP4 inhibitor users were created. SGLT2 inhibitor use was associated with a greater decline in FLI than DPP4 inhibitor use (difference at 1-year measurement, - 3.8 [95% CI - 4.7 to - 3.0]). The advantage of SGLT2 inhibitor use over DPP4 inhibitor use for improvement in FLI was consistent across subgroups. The relationship between SGLT2 inhibitors and amelioration of FLI was comparable between individual SGLT2 inhibitors. CONCLUSIONS: Our analysis using large-scale real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in patients with MAFLD and DM.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Male , Female , Middle Aged , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Retrospective Studies , Aged , Fatty Liver/drug therapy , Adult , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolismABSTRACT
Infections with D. dendriticum are distributed worldwide and mostly associated with ruminant livestock. Depending on the length and strength of the infection it can be manifested with losses in milk production, reductions in milk and wool quality, decreased weight gains, reproductive performance and poor carcass quality. The objective of this study was to determine the efficacy of albendazole (ABZ) against the lancet liver fluke Dicrocoelium dendriticum in naturally infected sheep using parasitological methods. Twenty-four sheep were divided into four groups: two untreated control groups (C1, C2) and two treated groups (T1, T2), with six animals in each group. The sheep in the treated groups were administered a single oral dose (15 mg/kg bwt) of ABZ suspension. After ABZ treatment the animals were slaughtered on Day 14 (groups C1, T1) and Day 30 (groups C2, T2) and were necropsied. Coprological therapeutic ABZ efficacy reached 92.4% on Day 14 (P < 0.001) and 88.5% on Day 30 (P < 0.001). On Day 30, the serum activities of hepatic and cholestatic enzymes including serological analysis of total protein concentration (TP) and protein fractions were evaluated. Significant decrease of aspartate aminotransferase (AST) (P < 0.01) and gamma-glutamyltransferase (GGT) (P < 0.05) activity by 36.9% and 34.6%, respectively, were detected for sheep in T2 group. These enzymes showed a strong positive correlation to fluke burden: AST (r = 0.654) and GGT (r = 0.768), respectively (P < 0.05). Additionally, the electrophoretic analysis of serum total protein and protein fraction concentrations revealed minimal hypoproteinemia and hyperalbuminemia after ABZ treatment. The decrease of liver enzyme activities and their correlation with fluke burden may indicate recovery of hepatocellular and biliary damage following the reduction of fluke burdens after ABZ therapy. A decline in AST and GGT activity could serve as a valuable adjunct bioindicator of liver damage and fluke reduction after treatment of dicrocoeliosis in naturally infected sheep.
Subject(s)
Dicrocoelium , Fasciola hepatica , Sheep Diseases , Animals , Sheep , Albendazole/pharmacology , Albendazole/therapeutic use , Dicrocoelium/metabolism , Fasciola hepatica/metabolism , Sheep Diseases/drug therapy , Liver/metabolism , gamma-GlutamyltransferaseABSTRACT
The prevalent use of pesticides, including pirimiphos-methyl (PPM) and bifenthrin (BF), poses a serious health risk, particularly to workers who encounter these chemicals daily. Despite the recognized hepatotoxic effects, the specific molecular mechanisms, especially those involving miRNAs in liver damage caused by PPM and BF, are not fully elucidated. Prior studies have not exhaustively analyzed the hepatic miRNA-target gene dynamics following exposure to these pesticides; thus, this research aims to fill that gap through an extensive miRNA analysis to discern their regulation in PPM or BF-induced hepatic toxicity. In this study, male Sprague-Dawley rats were exposed to BF or PPM for 28 days through oral gavage, simulating the chronic exposure faced by humans. We conducted a thorough assessment of the hepatotoxicity induced by PPM and BF, employing multiple evaluation levels, including histological analysis, liver enzyme measurements, and real-time PCR to detect changes in hepatic miRNA-target gene expressions. Additionally, we utilized DIANA-miRPath prediction tools to delineate the functional implications of these hepatic miRNA target genes. Our findings reveal a significant modulation in the expression of rno-miR-155-5p and rno-miR-122-5p, along with their target genes, following PPM and BF treatment. In contrast, rno-miR-21-5p levels remained unaltered. These observations suggest potential utility of these specific hepatic miRNAs as biomarkers for liver injury resulting from pesticide exposure. Subsequent GO enrichment analysis linked target genes to functions like molecular activity, protein binding, and cellular processes. Additionally, KEGG pathway analysis showed these genes, influenced by varied miRNA expressions, play significant roles in metabolic and signaling pathways In conclusion, this study enhances our comprehension of the biological roles of miRNAs in hepatic toxicity induced by PPM and BF. The insights gained here not only shed light on molecular mechanisms but also open avenues for considering these miRNAs as potential diagnostic biomarkers in conditions of pesticide-induced hepatotoxicity, thereby guiding future therapeutic strategies.
Subject(s)
Chemical and Drug Induced Liver Injury , MicroRNAs , Pesticides , Pyrethrins , Humans , Rats , Animals , Male , Pesticides/toxicity , Rats, Sprague-Dawley , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers , Computational Biology , Chemical and Drug Induced Liver Injury/geneticsABSTRACT
Foods enriched with insects can potentially prevent several health disorders, including cardiovascular diseases, by reducing inflammation and improving antioxidant status. In this study, Tenebrio molitor and Gryllus assimilis were selected to determine the effect on the development of atherosclerosis in ApoE/LDLR-/- mice. Animals were fed AIN-93G-based diets (control) with 10% Tenebrio molitor (TM) and 10% Gryllus assimilis (GA) for 8 weeks. The nutritional value as well as antioxidant activity of selected insects were determined. The lipid profile, liver enzyme activity, and the fatty acid composition of liver and adipose tissue of model mice were evaluated. Quantitative analysis of atherosclerotic lesions in the entire aorta was performed using the en face method, and for aortic roots, the cross-section method was used. The antioxidant status of the GA cricket was significantly higher compared to the TM larvae. The results showed that the area of atherosclerosis (en face method) was not significantly different between groups. Dietary GA reduced plaque formation in the aortic root; additionally, significant differences were observed in sections at 200 and 300 µm compared to other groups. Furthermore, liver enzyme ALT activity was lower in insect-fed groups compared to the control group. The finding suggests that a diet containing edible insect GA potentially prevents atherosclerotic plaque development in the aortic root, due to its high antioxidant activity.
Subject(s)
Apolipoproteins E , Atherosclerosis , Receptors, LDL , Animals , Atherosclerosis/pathology , Atherosclerosis/metabolism , Mice , Receptors, LDL/genetics , Receptors, LDL/metabolism , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Edible Insects , Mice, Knockout , Liver/metabolism , Liver/pathology , Antioxidants/metabolism , Male , Tenebrio , Diet , Aorta/pathology , Aorta/metabolism , Disease Models, Animal , Animal Feed , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/metabolism , GryllidaeABSTRACT
To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.
Subject(s)
Camelus , Animals , Camelus/blood , Female , Male , Pregnancy , Sex Determination Analysis/veterinary , Sex Determination Analysis/methods , Hydrocortisone/blood , Testosterone/blood , Creatinine/blood , Fetus , Estradiol/blood , Gonadal Steroid Hormones/bloodABSTRACT
Background: A growing number of athletes are using synthetic anabolic-androgenic steroids (AAS), comprised of testosterone and other derivatives, to enhance athletic performance and muscle mass. Over the years, numerous reports elucidated the side effects of the illegal use of AAS, such as infertility, and liver disorders. The effect of AAS on the hepatic and reproductive systems in Saudi athletes has not yet been studied. Therefore, this study examined the liver function and sex hormone parameters of AAS users as compared to non-users. Methods: Fasting blood samples were collected from 16 male Saudi athletes, 10 AAS-users (cases) and 6 non-users (controls) to measure liver function tests (ALT, AST, GGT, ALP, total protein, albumin, direct and total bilirubin) and muscle enzymes (CK, LDH), Fertility hormones (LH, FSH, total testosterone, estradiol, and prolactin) were included also. Furthermore, a self-reported questionnaire was obtained to identify the type of AAS used, the dosage, and the length of the course before sample collection. Results: The results show a statistically significant increase in ALT (P < 0.001), AST (P < 0.001), CK (P < 0.05), and a significant decrease (P < 0.05) in albumin (P < 0.001) and total bilirubin levels (P < 0.01) in AAS-users. Total testosterone increased significantly among AAS (P < 0.05), along with a significant decrease in LH (P < 0.01), and FSH (P < 0.001) levels, while serum prolactin and estradiol levels were significantly increased (P < 0.05). Conclusion: AAS can enhance physical performance and appearance, its potential adverse effects on the hepatic and reproductive systems necessitate careful consideration. Our research demonstrates an increase in the liver-specific enzyme ALT in AAS users relative to non-users and the possibility that short-term AAS usage increases the risk of liver injury.
ABSTRACT
AIMS/HYPOTHESIS: The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS: All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS: A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION: At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.
Subject(s)
Liver , Mediation Analysis , Humans , CholesterolABSTRACT
BACKGROUND & AIMS: Serum 25-hydroxyvitamin D [S-25(OH)D] and nonalcoholic fatty liver disease (NAFLD) are correlated in many observational studies, whereas the causality of this association is uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to determine the association between S-25(OH)D and NAFLD. METHODS: Seven and 6 independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide-significance level, respectively, were selected as instrumental variables. Summary-level data for S-25(OH)D were obtained from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium including 79,366 individuals. Summary-level data for NAFLD were available from a genome-wide association meta-analysis (1483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls), and the UK Biobank study (275 cases and 360,919 controls). Summary-level data for 4 liver enzymes were obtained from the UK Biobank. RESULTS: There were genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes. Genetically predicted higher levels of S-25(OH)D were consistently associated with a decreased risk of NAFLD in the 3 sources. For a 1-SD increase in genetically predicted S-25(OH)D levels, the combined odds ratio of NAFLD was 0.78 (95% confidence interval [CI], 0.69 to 0.89). Genetically predicted higher levels of S-25(OH)D showed a borderline association with aspartate aminotransferase levels (change -1.17; 95% CI, -1.36 to 0.01). Genetic predisposition to NAFLD was not associated with S-25(OH)D (change 0.13; 95% CI, -1.26 to 0.53). CONCLUSIONS: Our findings have clinical implications as they suggest that increased vitamin D levels may play a role in NAFLD prevention in European populations.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/genetics , Risk Factors , Genome-Wide Association Study , Vitamin D , Mendelian Randomization Analysis , Polymorphism, Single NucleotideABSTRACT
Chikungunya virus (CHIKV) is an arbovirus (Togaviridae family, Alphavirus genus) that was first identified in 1953 in Tanzania. In 2014, the Asian and East/Central/South/African (ECSA) genotypes were identified in Brazil, although the genotype that spread the most in the following years across the Brazilian territory was the ECSA. The clinical symptoms associated with the infection caused by CHIKV include mainly fever, myalgia, headache, and arthralgia. In infections caused by other arboviruses (such as the ones caused by Dengue and West Nile viruses), changes in biochemical markers are often observed. This study aims to evaluate the biochemical markers profile of kidney and liver injury in acute patients infected with CHIKV. Two groups of correlations were found between the variables analyzed, namely, one between liver enzymes (r = 0.91), and another for kidney markers (r = 0.54-0.66). A significant elevation in the percentage of altered creatinine in CHIKV-infected patients was observed, followed by uric acid and AST. Altogether, in 8 different comparisons, it was possible to observe statistically significant differences between the levels of the markers when compared to the manifestation of symptoms (presence and absence). These noticeable changes in marker measurements could potentially be connected to the range of clinical symptoms seen in the disease.
Subject(s)
Arboviruses , Chikungunya Fever , Chikungunya virus , Humans , Chikungunya virus/genetics , Chikungunya Fever/diagnosis , Phylogeny , Genotype , BiomarkersABSTRACT
BACKGROUND: Many observational studies explore the relationship between homocysteine (Hcy) and nonalcoholic fatty liver disease (NAFLD), whereas the causality of this association remains uncertain, especially in European populations. We performed a bidirectional Mendelian randomisation study to elucidate the causal association between Hcy and NAFLD. Furthermore, we explored the relationship of Hcy with liver enzymes, including alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). METHODS: Two-sample Mendelian randomisation study was conducted. Summary statistics for Hcy were obtained from a genome-wide association studies (GWAS) meta-analysis comprising 44,147 subjects. Summary-level data for NAFLD were acquired from a GWAS meta-analysis of 8434 cases and 770,180 noncases and another GWAS meta-analysis of 1483 cases and 17,781 noncases. Summary-level data for three liver enzymes were available from the UK Biobank. RESULTS: Genetic associations of Hcy concentrations with NAFLD and liver enzymes were observed. Genetically predicted higher Hcy concentrations were consistently associated with an increased NAFLD risk in two data sources. The combined odds ratio of NAFLD was 1.25 (95% confidence interval [CI], 1.05-1.45) per SD increase in Hcy concentrations. Genetically predicted higher Hcy concentrations showed significant association with ALP (Beta .69; 95% CI, 0.04-1.34), ALT (Beta 0.56; 95% CI, 0.15-0.97) and AST levels (Beta .57; 95% CI, 0.10-1.04). Genetic liability to NAFLD was not associated with Hcy concentrations. CONCLUSIONS: This study has clinical implications as it indicates that increased Hcy concentrations increase the relevant liver enzymes and may play a role in NAFLD risk in European populations.