Elevated Serum Alanine Aminotransferase Levels Research Articles

Porphyromonas gingivalis Strain W83 Infection Induces Liver Injury in Experimental Alcohol-Associated Liver Disease (ALD) in Mice

The liver plays a vital role in the defense against infections. Porphyromonas gingivalis (P. gingivalis), a dominant etiologic oral bacterium implicated in periodontal disease (PD), has been associated with various systemic diseases. This study aimed to investigate the influence of P. gingivalis on alcohol-associated liver diseases (ALD). Mice were fed a Lieber–DeCarli liquid diet containing 5% ethanol for 10 days after an initial adaptation period on a diet with lower ethanol content for 7 days. Two days before tissue sample collection, the mice were administered P. gingivalis strain W83 (Pg) through intraperitoneal injection (IP). Pair-fed mice with Pg infection (PF+Pg) exhibited an activated immune response to combat infections. However, alcohol-fed mice with Pg infection (AF+Pg) showed liver injury with noticeable abscess lesions and elevated serum alanine aminotransferase (ALT) levels. Additionally, these mice displayed liver infiltration of inflammatory monocytes and significant downregulation of proinflammatory cytokine gene expression levels; and AF+Pg mice also demonstrated increased intrahepatic neutrophil infiltration, as confirmed by chloroacetate esterase (CAE) staining, along with elevated gene expression levels of neutrophil cytosol factor 1 (Ncf1), neutrophilic inflammation driver lipocalin 2 (Lcn2), and complement component C5a receptor 1 (C5ar1), which are associated with neutrophilic inflammation. Interestingly, compared to PF+Pg mice, the livers of AF+Pg mice exhibited downregulation of gene expression levels of NADPH oxidase 2 (Cybb), the leukocyte adhesion molecule Cd18, and the Toll-like receptor adaptor Myd88. Consequently, impaired clearance of P. gingivalis and other bacteria in the liver, increased susceptibility to infections, and inflammation-associated hepatic necrotic cell death were observed in AF+Pg mice, which is likely to have facilitated immune cell infiltration and contributed to liver injury. Furthermore, in addition to the Srebf1/Fasn pathway induced by alcohol feeding, Pg infection also activated carbohydrate response element-binding protein (ChREBP) in AF+Pg mice. In summary, this study demonstrates that P. gingivalis infection, acting as a “second hit”, induces dysfunction of immune response and impairs the clearance of bacteria and infections in alcohol-sensitized livers. This process drives the development of liver injury.

Toosendanin induces hepatotoxicity by restraining autophagy and lysosomal function through inhibiting STAT3/CTSC axis

Toosendanin (TSN) is the main active component in the traditional herb Melia toosendan Siebold & Zucc, which exhibits promising potential for development due to its diverse pharmacological properties. However, the hepatotoxicity associated with TSN needs further investigation. Previous research has implicated autophagy dysregulation in TSN-induced hepatotoxicity, yet the underlying mechanisms remain elusive. In this study, the mechanisms of signal transducer and activator of transcription 3 (STAT3) in TSN-induced autophagy inhibition and liver injury were explored using Stat3 knockout C57BL/6 mice and HepG2 cells. TSN decreased cell viability, increased lactate dehydrogenase (LDH) production in vitro, and elevated serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels as well as liver lesions in vivo, suggesting TSN had significant hepatotoxicity. TSN inhibited Janus kinase 2 (JAK2)/STAT3 pathway and the expression of cathepsin C (CTSC). Inhibition of STAT3 exacerbated TSN-induced autophagy inhibition and hepatic injury, whereas activation of STAT3 attenuated these effects of TSN. Mechanistically, STAT3 transcriptionally regulated the level of CTSC gene, which in turn affected autophagy and the process of liver injury. TSN-administered Stat3 knockout mice showed more severe hepatotoxicity, CTSC downregulation, and autophagy blockade than wildtype mice. In summary, TSN caused hepatotoxicity by inhibiting STAT3/CTSC axis-dependent autophagy and lysosomal function.

Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study.

The results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia. By using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors. The results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results. This two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Hepatic and Renal Functions in HIV-Positive Children with Malaria in Western Kenya

Background: The burden of HIV and malaria co-infection lies disproportionately in the Sub-Saharan Africa region which bears most of the malaria endemic zones. While both malaria and HIV are known to dysregulate hepatic and renal functions, the combined effect of co-infection with malaria and HIV on hepatic and renal function among children remains poorly characterized. Objective: To assess liver and renal functions in HIV-malaria co-infected children in Western Kenya. Methods: A cross-sectional study was conducted among children aged 6-59 months with HIV and malaria coinfection at Kakamega County Referral Hospital, Western Kenya. A total of 138 children were enrolled. Microscopy and clinical chemistry analysers were used to diagnose malaria, and assay hepatic and renal function parameters respectively. Results: HIV positive-malaria positive cases had significantly higher serum creatinine and urea levels compared to the HIV positive-malaria negative controls. Likewise, serum levels of the alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total protein, albumin and globulin were significantly elevated in the HIV and malaria-positive cases compared to HIV-positive and malaria-negative controls. Significantly higher proportions of children with HIV and malaria coinfection also had elevated serum levels of ALT, ASP, GGT, total proteins, albumin and globulin compared to children without coinfection. Serum levels of Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) were comparable in both groups. Conclusion: Co-infection with HIV and malaria among children is generally associated with disrupted hepatic and renal function parameters.

Antiviral therapy reduces hepatocellular carcinoma through suppressing hepatitis B virus replication may improve ER stress, mitochondrial and metabolic dysfunctions and decrease p62 in hybridized mice with single HBV transgene and miR-122.

Hepatitis B virus (HBV) hijacks autophagy for its replication. Nucleos(t)ide analogs (NUCs) treatment suppressed HBV replication and reduced hepatocellular carcinoma (HCC) incidence. However, the use of NUCs in chronic hepatitis B (CHB) patients with normal or minimally elevated serum alanine aminotransferase (ALT) levels is still debated. Animal models are crucial for studying the unanswered issue and evaluating new therapies. MicroRNA-122 (miR-122), which regulates fatty acid and cholesterol metabolism, is downregulated during hepatitis and HCC progression. The reciprocal inhibition of miR-122 with HBV highlights its role in HCC development as a tumor suppressor. By crossbreeding HBV-transgenic mice with miR-122 knockout mice, we generated a hybrid mouse model with a high incidence of HCC up to 89% and normal ALT levels before HCC. The model exhibited early-onset hepatic steatosis, progressive liver fibrosis, and impaired late-phase autophagy. Metabolomics and microarray analysis identified metabolic signatures, including dysregulation of lipid metabolism, inflammation, genomic instability, the Warburg effect, reduced TCA cycle flux, energy deficiency, and impaired free radical scavenging. Antiviral treatment reduced HCC incidence in hybrid mice by approximately 30-35% compared to untreated mice. This effect was linked to the activation of ER stress-responsive transcription factor ATF4, clearance of autophagosome cargo p62, and suppression of the CHOP-mediated apoptosis pathway. In summary, this study suggests that despite minimal ALT elevation, HBV replication can lead to liver injury. Endoplasmic reticulum stress, reduced miR-122 levels, mitochondrial and metabolic dysfunctions, blocking protective autophagy resulting in p62 accumulation, apoptosis, fibrosis, and HCC. Antiviral may improve the above-mentioned pathogenesis through HBV suppression.

Effect of Miscellaneous Meal Replacements for Soybean Meal on Growth Performance, Serum Biochemical Parameters, and Gut Microbiota of 50-75 kg Growing Pigs.

This study was carried out to investigate the effects of miscellaneous meal (rapeseed meal, cottonseed meal, and sunflower seed meal) as a replacement for soybean meal on growth performance, apparent nutrient digestibility, serum biochemical parameters, serum free amino acid contents, and gut microbiota of 50-75 kg growing pigs. A total of 54 healthy growing pigs (Duroc × Landrace × Yorkshire) with initial body weights (BWs) of 50.64 ± 2.09 kg were randomly divided into three treatment groups, which included the corn-soybean meal group (CON), corn-soybean-miscellaneous meal group (CSM), and corn-miscellaneous meal group (CM). Each treatment included six replicates with three pigs in each replicate. Dietary protein levels were maintained at 15% in all three treatment groups. Additional rapeseed meals, cottonseed meals, and sunflower seed meals were added to the CSM group's meals to partially replace the 10.99% soybean meal in the CON group in a 1:1:1 ratio. Pigs in the CM group were fed a diet with a mixture of miscellaneous meals (7.69% rapeseed meal, 7.69% cottonseed meal, and 7.68% sunflower seed meal) to totally replace soybean meal. Our findings revealed that there was no significant impact of replacing soybean meal with miscellaneous meal on the ADG (average daily gain), ADFI (average daily feed intake), or F/G (feed-to-gain ratio) (p > 0.05) of growing pigs weighing 50-75 kg, nor on the crude protein, crude fat, or gross energy (p > 0.05) of the diet. On the other hand, compared to the CON group, the CM group exhibited significantly elevated serum alanine aminotransferase (ALT) and triglyceride (TG) levels (p < 0.05), while urea levels were significantly reduced (p < 0.05). No significant effect was observed on the serum free amino acid contents (p > 0.05) following the substitution of soybean meal with miscellaneous meal. A t-test analysis indicated that compared with the CON group, the CM group exhibited a significantly diminished abundance of Euryachaeota at the phylum level and augmented abundance of Desulfobacterota at the genus level. This study demonstrated that the miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower seed meal) as a substitute for soybean meal in the diet had no significant negative effects on the growth performance, apparent nutrient digestibility, serum amino acid content, or diversity of fecal microbiota in 50-75 kg growing pigs. These results can be helpful in developing further miscellaneous meals (rapeseed meal, cottonseed meal, and sunflower seed meal) as functional alternative feed ingredients to soybean meal in pig diets.

Nonviral Liver Disease Burden in People Living With HIV and Elevated Transaminases: A Cross-Sectional Study.

Because of improved life expectancy in people living with HIV (PLWH), liver disease is increasingly being recognized. We assessed nonviral chronic liver disease burden in PLWH. The HIV non-virAL liver disease study (2014-2021) prospectively recruited PLWH with elevated serum alanine aminotransferase levels and negative hepatitis serology. Clinically significant hepatic fibrosis (CSHF) was defined as liver stiffness measurement of >7.1 kPa and hazardous alcohol use as Alcohol Use Disorders Identification Test score ≥ 8. Primary outcome was prevalence/predictors of CSHF. Total recruited were n = 274, 92% male, median age 52 (45-59) years, and 96% having undetectable HIV viral load. Overall, n = 97 (35%) had hazardous alcohol use, n = 72 (26%) had metabolic syndrome, and 17%-27% had exposure to hepatotoxic antiretrovirals. Prevalence of CSHF was 20% (n = 54), prevalence of cirrhosis (liver stiffness measurement > 12.5 kPa) being 7% (19/274). Risk factors for CSHF were hazardous alcohol use in 44% (n = 24), metabolic syndrome in 46% (n = 25), and hepatotoxic antiretrovirals in 56% (n = 30), most having more than one risk factor. Independent predictors of CSHF were serum high-density lipoprotein (odds ratio [OR] 0.220; 95% confidence interval [CI]: 0.061 to 0.790, P = 0.020) (inverse relationship); serum aspartate aminotransferase (OR 1.033, 95% CI: 1.001 to 1.067, P = 0.045), and didanosine use (OR 2.878, 95% CI: 1.228 to 6.774, P = 0.015). Moderate-severe hepatic steatosis was identified in 52% (n = 142). FIB-4 and aspartate aminotransferase-to-platelet ratio index performed poorly in predicting CSHF (positive predictive value 27.3% and 30.6%, respectively) and advanced fibrosis (≥F3) (positive predictive value 17.6% and 5.9%, respectively). In this study, 20% of PLWH had CSHF associated with high prevalence of hazardous alcohol use/metabolic syndrome/potentially hepatotoxic antiretrovirals. These potentially modifiable risk factors need addressing.

Multiorgan failure caused by Chinese herbal medicine Xanthii Fructus poisoning: a case report

BackgroundXanthii Fructus was used in the treatment of rhinitis and related nasal disease. It is the most commonly used chemically active component in compounds formulated for the treatment of rhinitis. However, poisoning, resulting in serious consequences, can easily occur owing to cocklebur overdose, improper processing, or usage without processing.Case presentationWe reported on a 55-year-old man who experienced allergic rhinitis for 2.5 years. He ingested unprocessed Xanthii Fructus for 2 months as treatment. However, he developed anorexia; nausea; abdominal pain; general weakness; hiccups; oliguria and anuria; significantly elevated serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels; and abnormalities in blood coagulation series. Nutritional support; daily drugs for liver protection, gastric protection, inflammation reduction; fresh plasma; and cryoprecipitate infusion were administered. Continuous venovenous hemodialysis (Prismaflex ST100) was also administered. However, the patient’s multiple organ failure gradually worsened, ultimately leading to death.ConclusionXanthii Fructus poisoning affects multiple systems, and its clinical manifestations are complex. Therefore, it is easily misdiagnosed and missed. Along with careful inquiry of medical and medication history, early diagnosis and intervention are vital for a successful treatment. It is also important to educate people and create awareness about this poisoning. Therefore, this intractable case has great clinical significance.

The causal associations of non-alcoholic fatty liver disease with blood pressure and the mediating effects of cardiometabolic risk factors: A Mendelian randomization study

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is prevalent in hypertensive people, but the causal effect remains unclear. We employed Mendelian randomization (MR) approach to assess the causality between NAFLD and different blood pressure (BP) parameters. Method and resultsInstrumental variables for genetically predicted NAFLD, including chronically elevated serum alanine aminotransferase levels (cALT) and imaging and biopsy-confirmed NAFLD, were obtained from a genome-wide association study (N = 164,197). Multiple MR methods were implemented, including Inverse variance weighted, MR-Egger, Maximum likelihood, Weighted median, Simple median, Penalised weighted median, MR-RAPS, and cML-MA. Outliers were detected using MR-PRESSO, and pleiotropy was assessed using MR-Egger intercept and Phenoscanner. Heterogeneity was quantified using Cochran's Q and Rucker's Q′ tests. Potential shared risk factors were analyzed to reveal the mediating effect. A higher genetic predisposition to cALT was causally associated with an increased risk of elevated BP levels, resulting in 0.65 mmHg (95% CI, 0.42–0.87), 0.38 mmHg (95% CI, 0.25–0.50) and 0.33 mmHg (95% CI, 0.22–0.44) higher for systolic BP, diastolic BP and pulse pressure, respectively. When more stringent criteria were used, imaging and biopsy-confirmed NAFLD showed a 1.12 mmHg (95% CI, 0.94–1.30) increase in SBP and a 0.55 mmHg (95% CI, 0.39–0.70) increase in DBP. Risk factor and mediation analyses suggested type 2 diabetes and fasting insulin levels might mediate the causal relationship between NAFLD and BP. ConclusionThe two-sample MR analyses showed robust causal effects of genetically predicted NAFLD on 3 different BP indices. The shared genetic profile between NAFLD and BP may suggest important therapeutic targets and early interventions for cardiometabolic risk factors.

Geometric Isomer of Guanabenz Confers Hepatoprotection to a Murine Model of Acetaminophen Toxicity.

Overdose of acetaminophen, a widely used antipyretic and analgesic drug, is one of the leading causes of drug-induced acute liver injury in the United States and worldwide. Phase-I metabolism of acetaminophen generates the toxic N-acetyl-p-benzoquinone imine (NAPQI) intermediate. Reactions of NAPQI with a wide range of biomolecules cause increased oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and mitochondrial dysfunction, some of the cellular events contributing toward liver toxicity. Previously, we evaluated the potential of an FDA-approved, ER stress-modulating antihypertensive drug, Wytensin (trans-guanabenz, E-GA), as an antidote for acetaminophen hepatotoxicity. E-GA prevented elevation of the liver enzyme alanine aminotransferase (ALT), even when administered up to 6 h after acetaminophen overdose, and exhibited synergistic analgesic interactions. However, the commercially available guanabenz exists solely as a trans-isomer and suffers from sedative side effects resulting from the inhibition of central α2A-adrenergic receptors in locus coeruleus. Here, we studied the utility of the relatively unexplored cis-isomer of guanabenz as a treatment option for acetaminophen-induced liver toxicity. cis(Z)-Guanabenz acetate (Z-GA) lacks interaction with α2A-adrenoreceptors and is thus devoid of sedative, blood-pressure-lowering side effects of E-GA. Treatment of mice with Z-GA (10 mg/kg) before acetaminophen overdose and up to 6 h post APAP administration prevented liver injury and suppressed the elevation of serum ALT levels. Mechanistically, hepatoprotective effects of both isomers are similar and partly attributed to attenuation of the ER stress and oxidative stress in the liver. The results of this study suggest that Z-GA may be a safer, effective antidote for the clinical management of acute liver injury resulting from acetaminophen overdose. It also raises a tantalizing possibility of a prophylactic combination of the geometric isomer of the approved drug guanabenz with acetaminophen in a clinical setting.

Functional Cure of Chronic Hepatitis B with Antiviral Treatment in Children having High-level Viremia and Normal or Mildly Elevated Serum Aminotransferase.

There is a lack of data supporting the notion that antiviral treatments can benefit children with chronic hepatitis B (CHB) having high viremia and normal or mildly elevated serum alanine aminotransferase (ALT) levels. We aimed to analyze the efficacy of antiviral treatments in children with CHB and explore the factors associated with functional cure. Forty-eight children with CHB having high viremia and normal or mildly elevated serum ALT levels were screened in this real-world study. Thirty-two children received either interferon-alpha (IFN-α) monotherapy, IFN-α therapy with a nucleoside analog (NA) add-on, or IFN-α and NA combination therapy. The 16 children in the control group did not receive antiviral treatment. All 48 children were available for follow-up assessments for the entire 36-month study period. We identified a functional cure with respect to hepatitis B virus (HBV) DNA loss, loss /seroconversion of circulating hepatitis B e antigen (HBeAg), and loss of hepatitis B surface antigen (HBsAg) with or without seroconversion. Cox regression analysis was employed to evaluate the factors that may have influenced the functional cure. After 36 months, the cumulative functional cure rate was 56.25% (18/32) in the treated group and 0% (0/16) in the control group (p<0.001). In the treated group, the serum HBV DNA levels declined rapidly at the end of a 6-month visit and the cured children achieved a loss rate of 100% (18/18) within 16 months of beginning treatment, compared with 64.29% (9/14) of the uncured children (p<0.001). The rates of HBeAg seroconversion were significantly higher among the cured children than among the uncured children (p<0.001). All 16 children in the control group maintained high levels of serum HBV DNA and were positive for both serum HBeAg and HBsAg during the entire 36 months of the study period. Functional cure was associated with younger ages (1-6 vs. 7-14 years, p=0.013), CD8+ T lymphocyte counts (p=0.013), and B lymphocyte counts (p=0.003). No serious adverse events were observed. Antiviral treatment achieved a functional cure of CHB in a high proportion of children having high-level viremia and normal or mildly elevated ALT levels. Younger age and high peripheral lymphocyte counts were associated with this functional cure.

Effect of Long-term Ketogenic Diet on Serum Alanine Transaminase Levels in Mice (Mus musculus)

The prevalence of obesity is increasing worldwide over the years. One of the non-pharmacological therapy which is believed to be promote weight loss is ketogenic diet. Nevertheless, the long-term effects which may be caused by this diet are still debating, especially in the liver. This study aimed to determine the effect of long-term ketogenic diet (8 weeks) on serum alanine transaminase (ALT) levels. Twelve male mice were divided into basal diet (BD) and ketogenic diet (KD) group and given intervention for eight weeks adlibitum. Body weight was weighed in pre and post-intervention, while ALT levels were measured only once after eight weeks of intervention. As a result, pre-intervention body weight in the BD group was 25.170 ± 2.858 g and KD group was 27.170 ± 1.329 g (P =0.151). In the post-intervention, body weight in BD and KD group were 44.500 ± 5.244 g and 31.830 ± 5.707 g, respectively (P =0.003). BD group showed a significant difference between pre-and post-intervention body weight (P &lt;0.0001); however, it was not significant in the KD group (P =0.096). After eight weeks, serum ALT levels in BD-fed mice were 90.672 ± 20.786 U/L and in KD-fed mice showed 117.037 ± 19.261 U/L (P =0.046). In conclusion, KD elevated serum ALT levels and attenuated weight gain after 8-week KD supplementation. Keywords: Alanine transaminase, Ketogenic diet, Liver, Mice, Obesity

Procyanidins Ameliorate Acetaminophen-induced Acute Liver Injury via Activating the Nrf-2/SOD-1 Signal Pathway

Background and Objectives An overdose of acetaminophen (APAP) usually leads to acute liver injury, and oxidative stress is one of the fundamental mechanisms used to characterize it. Procyanidins (PCs) can reduce the oxidative stress in the liver of mice. This study aimed to investigate the potential protective role of PCs against APAP-induced acute liver injury. Materials and Methods Experiments were performed on male Kunming mice in six groups: phosphate-buffered saline, PCs, APAP, and PCs pretreated with 10, 50, and 100 mg/kg. The mice were peritoneally injected with PCs 30 min before the administration of APAP. First, survival rates of mice were scored every 12 hr for three days in succession. Furthermore, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (T-Bil), total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) were determined. Additionally, histological analysis and hepatic oxidative stress including the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) were assessed. Finally, the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD-1 was detected by Western blotting. Results The data indicated that PCs improved survival rates of APAP-induced liver injury in mice models. Moreover, PCs could reduce the elevated serum levels of ALT, AST, T-Bil, TC, TG, TNF-α, IL-1β, and IL-6 due to APAP exposure with a dose-dependent manner. Besides, PCs pretreatment attenuated hepatic histopathological damage and oxidative stress which manifested the increases of SOD and GSH, whereas the decrease of MDA. Furthermore, PCs enhanced the protein expression of Nrf2 and SOD-1 in the PCs pretreatment groups compared with the APAP group. Conclusion PCs ameliorated APAP-induced acute liver injury, and Nrf2 signaling pathway modulating antioxidative stress might be involved in it.

Drinking Water Sources along the Banks of Buriganga River of Bangladesh are Polluted and Possess Serious Health Risks: A Comprehensive In Vivo Analysis.

The river Buriganga, one of the major dumping zones of industrial wastes in Bangladesh, is responsible for contaminating the drinking water sources along its length. This study aimed to assess the water quality from these sources by monitoring the changes in hematological, biochemical, and histological parameters caused in healthy rats due to their consumption. Using ethylenediaminetetraacetic acid (EDTA) as an anticoagulant agent, hematological and biochemical analyses of Sprague-Dawley rat models were executed in this study. Following blood sampling, the rats were sacrificed, and the heart, lungs, kidneys, liver, and spleen were separated to carry out the histological analysis. Later, to perform the statistical analysis, SPSS, V.25.0 was utilized. A significant rise (p < 0.02) in body weight was recorded due to increased protein synthesis, inflammations; increased lymphocyte, white blood cell (WBC), and neutrophil count but hemoglobin (20.0 ± 1.39 g/dL vs. 15.25 ± 0.36 g/dL; p) and red blood cell (RBC) count ((6.24 ± 0.45) × 106/µL vs. (5.47 ± 0.34) × 106/µL)) decreased due to infections and hematopoietic stem cell poisoning by pathogens in water samples. Elevated (p < 0.01) serum urea, creatinine, alanine, and aspartate aminotransferase levels indicated kidney malfunction and hepatic tissue necrosis. Histological analysis revealed gross lesions, internal hemorrhages in the brain; inflammations, granulomas, migrating macrophages in the spleen; fibrosis (resulting in hypo-perfusion), and collagen formation in cardiac muscles. The findings in this study provide comprehensive evidence, based on in vivo analysis, that the water bodies around the Buriganga river are likely to be contaminated with toxic chemicals and microbial entities making them unfit for human consumption.

Evaluation of Hepatoprotective activity of Cuscuta Reflexa

Cuscuta Reflexa from Convolvulaceae family is a plant with a variety of ethnic medicinal uses along with antioxidant activity. Hence it was planned to evaluate the hepatoprotective activity with methanolic extracts of whole plant of Cuscuta reflexa (MECR) and aqueous extracts of whole plant of Cuscuta reflexa (AQECR). Hepatoprotective activity of both the extracts was studied against galactosamine induced hepatotoxicity in rats. Biochemical parameters Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Serum alkaline phosphatase (ALP), Serum direct bilirubin (BILD), Serum total bilirubin (BILT), Serum albumin (ALB), Serum total proteins (PRO), Serum cholesterol (CHO), and histopathological changes of livers were assessed in control/toxicant/standard/and extract treated animals with galactosamine induced hepatotoxic models in rats. In LD50 studies for MECR and AQECR up to the maximum dose level of 2000 mg/kg dose no mortality was observed in any of the animals, indicating the practically nontoxic. When compared to toxicant control groups both the extracts have significantly reduced the paracetamol induced elevated levels of serum ALT, AST, ALP, BILT, BILD, CHO, and elevated the levels of ALB and PRO. The histopathological changes (steatosis), necrosis etc. Were partly or fully prevented in animals treated with the two extracts. MECR and AQECR showed a significant hepatoprotective effect against galactosamine induced hepatic damage. The medium and high doses of AESCR and AQESCR (200 and 400 mg/kg) treated groups showed better hepatoprotective activity when compared to standard drug silymarin (25 mg/kg). Studies for MECR and AQECR up to the maximum dose level of 2000 mg/kg dose no mortality was observed in any of the animals, indicating the practically nontoxic. When compared to toxicant control groups both the extracts have significantly reduced the paracetamol induced elevated levels of serum ALT, AST, ALP, BILT, BILD, CHO, and elevated the levels of ALB and PRO. The histopathological changes (steatosis), necrosis etc. Were partly or fully prevented in animals treated with the two extracts.

Hepatitis E virus seroprevalence among employees in catering and public place industries in Nanjing, China.

This study aimed to assess the prevalence of anti-hepatitis E virus (HEV) immunoglobulin (Ig) M and elevated serum alanine aminotransferase (ALT) levels among employees in catering and public place industries. Blood samples were collected between January and December 2020 from 26,790 employees working in the Qinhuai district of Nanjing, China. Anti-HEV IgM in the serum samples was tested by the capture ELISA method and ALT was tested by the IFCC method. Samples positive for anti-HEV IgM or with ALT levels over 200U/L were subjected to PCR screening of HEV RNA. The overall seroprevalence of anti-HEV IgM was 0.41%, and the seroprevalence was slightly higher in males (0.47%) than in females (0.37%); however, the difference was not substantial (p=0.177). Seroprevalence of anti-HEV IgM increased with age, reaching its peak level after 48years of age. The prevalence of elevated ALT levels was 4.24%, and males exhibited a higher prevalence than females (6.78% vs 2.65%, p<0.001). Prevalence of elevated ALT levels differed in age groups and the 26-36-year-old group had the highest rate of elevated ALT levels. Employees with elevated ALT levels had a higher prevalence of positive anti-HEV IgM than those with normal ALT (0.57% vs 0.31%, p<0.001). Positive HEV RNA was detected in one anti-HEV IgM-negative employee with ALT higher than 200U/L. In our study, all the HEV RNA-positive and IgM-positive individuals are asymptomatic, and a combination of ALT tests, serological methods, and molecular methods is recommended to screen asymptomatic HEV carriers and reduce the risk of transmission.

Elevated levels of serum glucose, triglyceride, and liver enzymes in a rat model of 7,12 dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis

ABSTRACT Background: Uncontrolled cell proliferation in cancers has a high requirement of energy and biosynthetic substrates. Glucose and triglycerides are the main source of energy as well as the primary building blocks for forming cellular components of mammalian cells.Objective: This study aims to evaluate the shifting of serum glucose, triglyceride, and nitrogen wastes in the form of urea and creatinine levels; and liver enzymes levels, alanine transaminase (ALT) and aspartate aminotransferase (AST), in rat model carcinogenesis with a single dose of 7,12-dimethylbenzanthracene (DMBA) for 16 weeks observation..Methods: The experimental animals of Rattus norvegicus strain Sprague Dawley were divided into two groups, namely the control group and the DMBA-induced group. A blood chemistry examination was carried out at weeks 4, 8, 12, and 16 post-induction using a spectrophotometer. In addition, observation of breast tumor formation and histological examination of the tumor and organs, including liver, lung, intestine, and kidney, were performed to confirm cancer formation.Results: Five of the six experimental rats (83.3%) induced by DMBA experienced breast and lung cancer formation accompanied by continuous weight loss starting at week 10 after induction. Serum glucose levels increased significantly at weeks 12 and 16 after induction, while serum triglyceride, ALT, and AST levels increased significantly from week 4 after induction until the end of the experiment. Serum urea levels did not show a significant difference from the control group. Nonetheless, creatinine decreased at the last examination.Conclusion: Elevated serum glucose, triglycerides, ALT, and AST levels escorted the chemical carcinogen-induced cancer development. Studies at the clinical level are needed to prove whether abnormally elevated of these blood chemistry levels can be used to detect the presence of cancer early.Keywords:DMBA, breast cancer, lung cancer, cancer metabolism.

Creatinine accelerates APAP-induced liver damage by increasing oxidative stress through ROS/JNK signaling pathway.

Serum creatinine is an endogenous biomarker to estimate glomerular filtration rate (GFR) and is commonly used to assess renal function in clinical practice. Acetaminophen (APAP), the most available analgesic and antipyretic medication, is recommended as the drug of choice for pain control in patients with renal diseases. However, an overdose of APAP can lead to severe acute liver injury, which is also the most common cause of acute liver failure in western countries. The role of creatinine in APAP-induced liver injury is unclear and should be further explored. Herein, clinical data on patients with drug-induced liver injury revealed that the creatinine concentration between 82-442 μmol/L for female and 98–442 μmol/L for male is positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST). While there was no correlation between creatinine and ALT and AST when creatinine concentration is over 442 μmol/L. In addition, mice were administrated with creatinine intraperitoneally for 1 week before APAP injection to investigated the pathophysiological role of creatinine in APAP-induced acute liver injury. The results showed that creatinine administration aggravated hepatic necrosis and elevated serum lactate dehydrogenase (LDH) and ALT levels in mice upon APAP injection. The mechanism study demonstrated that creatinine could increase the production of reactive oxygen activation (ROS) and the activation of c-Jun N-terminal kinase (JNK). Furthermore, the liver injury was alleviated and the difference between APAP-treated mice and APAP combined with creatinine-treated mice was blunted after using specific ROS and JNK inhibitors. Significantly, creatinine stimulation aggravates APAP-induced cell death in HepaRG cells with the same mechanism. In summary, this study proposed that creatinine is closely related with liver function of drug-induced liver injury and exacerbates APAP-induced hepatocyte death by promoting ROS production and JNK activation, thus providing new insight into the usage of APAP in patients with kidney problems.

The protective effect of ethanol leaf extract of Annona muricata against doxorubicin toxicity via modulations of hematological, serum biochemical, antioxidant enzymes, and lipid peroxidation

BackgroundDoxorubicin (DOX)-induced organ toxicity is of critical concern in cancer therapy because of its contributions to morbidity and mortality of cancer patients. This study evaluated the beneficial effect of Annona muricata (A. muricata) ethanol leaf extract on the toxic effect of DOX. MethodsScavenging abilities of A. muricata fractions (chloroform, ethyl acetate, ethanol, methanol, and aqueous) were tested against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Male rats (Rattus norvegicus) were randomly allotted into four groups of treatments. Group A served as a control, Group B was treated with 2.5 mg/kg body weight (b.w) DOX intraperitoneally (i.p) twice per week, Group C was treated with 200 mg/kg b.w extract (orally), once per day, and 2.5 mg/kg b.w DOX (i.p) twice per week. While Group D was treated with 200 mg/kg b.w. ethanol leaf extracts orally once daily for 2 weeks. Hematological indices (White blood cells (WBC), Red blood cells (RBC), Platelet (PLT), lymphocyte (LYM), hemoglobin (HGB), and hematocrit (HCT)), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, lactate dehydrogenase (LDH), creatine kinase (CK), cholesterol, CA (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated. ResultsAqueous and ethanol fractions displayed significant DPPH (p < 0.05) and ABTS (P < 0.05) inhibitory activity respectively when compared with other fractions. Ethanol fraction was used for the in vivo study considering significant activity against ABTS. DOX-induced tissue toxicity was shown by significant (P < 0.05) hematological indices unsettling and elevated levels of serum ALT, AST, urea, LDH, CK, and MDA. Serum oxidative stress markers including SOD, CAT, and GSH were significantly (P < 0.05) reduced in DOX treated group. The leaf extract normalized hematological indices and activated levels of ALT, AST, urea, LDH, CK, and MDA due to DOX treatment. Significant elevations of SOD, CAT, and GSH were also observed following extract treatment compared to DOX exposed group. ConclusionThis study suggests that the extract potential to prevent the severity of DOX-induced toxicity may be through oxidative stress suppression.

Serum alanine aminotransferase level and intravenous immunoglobulin resistance in patients with kawasaki disease.

Serum alanine aminotransferase (ALT) elevation is considered a risk factor for resistance to initial intravenous immunoglobulin (IVIG) treatment in patients with Kawasaki disease (KD). However, serum ALT levels change dramatically during acute KD illness. We tested the hypothesis that risk assessment for initial IVIG resistance based on serum ALT elevation may differ by examination day after KD onset. We analyzed 18,492 population-based patients who developed KD throughout Japan. First, we epidemiologically evaluated the serum ALT variation at 1‒10days after disease onset. Second, we conducted multivariable logistic regression to determine the association between serum ALT level and initial IVIG resistance according to timing of initial hospital visit by stratifying the patients into an early group (1‒5days after onset) and a late group (6‒10days after onset). Serum ALT rapidly increased after KD onset, peaked at day 4 of illness, and then declined regardless of IVIG responsiveness. The adjusted odds ratio (OR) increased with increasing serum ALT in the early group (adjusted OR [95% CI]: 1.44 [1.25-1.66], 1.94 [1.65-2.28], and 2.22 [1.99-2.48] for serum ALT 50-99, 100-199, and ≥ 200IU/L, respectively; reference ALT level: 1-49IU/L). No significant association was observed in the late group. The findings indicate that risk assessment for initial IVIG resistance based on serum ALT level may only be reliable for patients with KD who visit hospitals during early illness, specifically 1-5days after disease onset. Key Points Serum alanine aminotransferase level differed markedly according to examination days after Kawasaki disease onset. Serum alanine aminotransferase level declined toward normal range after day 5 of illness regardless of intravenous immunoglobulin responsiveness. Elevated serum alanine aminotransferase level was no longer a significant risk factor for initial intravenous immunoglobulin resistance when measured on delayed hospital visits. Risk assessment for initial intravenous immunoglobulin resistance based on serum alanine aminotransferase level may only be reliable for patients who visit hospitals during early illness, specifically 1-5days after disease onset.