Significant Liver Damage Research Articles

Silver nanoparticle toxicity in rainbow trout: insights into physiological and molecular responses.

Metallic nanoparticles, with their large surface area to volume ratio, are increasingly important in various life fields, but they can cause varying toxic effects on fish. This study investigates the toxicological effects of silver nanoparticles (AgNPs) on rainbow trout (Oncorhynchus mykiss), focusing on hematological, biochemical, antioxidant, and histopathological changes. Fish were exposed to varying concentrations of AgNPs (0.2, 0.8, and 1.4 mg/L) for 21days. Hematological analysis revealed significant reductions in red blood cell (RBC) counts, hemoglobin (Hb), and hematocrit (HCT) at higher AgNPs concentrations, while white blood cell (WBC) counts increased, indicating immune system activation. Biochemical assays demonstrated dose-dependent decreases in total protein and albumin, alongside increased cholesterol and triglyceride levels, suggesting impaired liver function and disrupted lipid metabolism. Antioxidant enzyme activity (SOD, CAT, GST) initially increased at lower AgNPs concentrations but declined at higher exposures, indicating oxidative stress. Molecular analysis further supported these findings, with upregulation of oxidative stress-related genes (SOD1, CAT) and inflammatory markers (HSP70, IL-1β). Histopathological examinations revealed necrosis, hyperplasia, and lamellar fusion in the gills, along with significant liver damage, including vacuolation and Kupffer cell proliferation, particularly at the highest exposure. Behavioral assays showed erratic swimming and reduced feeding in fish exposed to higher AgNPs concentrations. This study highlights the dose-dependent toxic effects of AgNPs on rainbow trout and underscores the potential for long-term, possibly irreversible damage at higher exposure levels. These findings emphasize the need for stricter environmental regulations on nanoparticle use to mitigate their ecological impact.

RELATO DE CASO: ASCITE AGUDA EM CÃO COM ETIOLOGIA INDETERMINADA

Ascites is a common problem in people with liver failure, marked by the accumulation of fluid in the peritoneal space, caused by increased hydrostatic pressure and sodium retention. This condition is commonly associated in dogs with increased production of aldosterone and reduced renal elimination of sodium, and is intensified by hypoalbuminemia, resulting from a reduction in the liver's ability to produce albumin. The negative impacts of ascites on the quality of life of animals include problems with mobility, breathing and rest. This paper describes a clinical case of a one-year-old, 15 kg non-breed dog (NBD) who exhibited symptoms of acute ascites, including increased abdominal volume, shortness of breath and exercise intolerance. The condition was examined through an anamnesis and a physical assessment, which confirmed the existence of ascites. Additional tests were carried out, such as a blood count, blood biochemistry, chest X-ray and abdominal ultrasound, to check organ function and the existence of fluid in the abdominal cavity. During hospitalization, the patient was given furosemide and fluid therapy, but did not respond and died before the diagnosis was confirmed. Tests revealed hypoproteinemia and significant liver damage, indicating that the ascites was linked to the organ's inability to maintain oncotic pressure. This case highlights the complexity of diagnosing and treating acute ascites in dogs, emphasizing the need to improve clinical and diagnostic strategies in similar situations, as well as stimulating future studies in this field.

Antioxidant and Protective Effects of Oleaster Oil Against Silica Nanoparticle-Induced Oxidative Stress and Organ Toxicity in Rats

Nanoparticles have found widespread application in a variety of fields, despite growing worry about their possible hazardous effects on both the environment and human health. In recent years, research efforts have focused on plants and vegetable oils, which have been identified as abundant sources of many bioactive compounds. Many of these substances are known to participate in antioxidant processes. As a result, the current study was designed to investigate the antioxidant and protective properties of oleaster oil against cytotoxicity and oxidative stress induced by silica nanoparticles (SiNPs) in albino Wistar rats. Forty male rats were randomly assigned to four equally sized cohorts: a control group, SiNP-treated group (at a dose of 50 mg/kg), SiNP-treated group supplemented with oleaster oil (at a dose of 2 mL/kg), and those receiving only 2 mL/kg of oleaster oil. The findings demonstrated that SiNPs initiated an oxidative stress environment, as evidenced by higher lipid peroxidation levels and changes in antioxidant defense mechanisms. Antioxidant enzymes were significantly reduced, including glutathione levels between the control and SiNP-exposure treatments (36.01%, 36.59%, 60%), glutathione-S-transferase (29.74%, 29.90%, 13.49%), catalase (24.14%, 28.19%, 30.85%), and tissue superoxide dismutase (11.90%, 37.78%, 37.79%) in the liver, kidney, and heart, respectively. Furthermore, histological investigations revealed significant liver, kidney, and heart damage, as indicated by pathological alterations such as vascular dilatation and congestion, inflammatory cellular infiltration, and hepatocellular dysfunction. Encouragingly, the administration of oleaster oil significantly ameliorated a majority of these detrimental effects. These data suggest a potential protective effect of oleaster oil against the adverse histological effects induced by SiNP injection.

Synthesis, Biological Evaluation, Molecular Docking Studies and ADMET Prediction of Oxindole-Based Hybrids for the Treatment of Tuberculosis.

With a projected mortality toll of 1.4 million in 2019, tuberculosis (TB) continues to be a significant public health concern around the world. Studies of novel treatments are required due to decreased bioavailability, increased toxicity, increased side effects, and resistance of several first- and second-line TB therapies, including isoniazid and ethionamide. This study reports the synthesis of oxindole-based hybrids as potent InhA inhibitors targeting Mycobacterium tuberculosis. The synthesized compounds (5a-5e and 8a-8c) were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis and nontuberculous mycobacteria (NTMs), viz. M. abscessus (ATCC 19977), M. fortuitum (ATCC 6841), and M. chelonae (ATCC 35752) using the Microplate Alamar Blue Assay (MABA). Molecular docking studies were performed using AutoDock Vina to explore the binding interactions of these compounds with the InhA enzyme (PDB: 2NSD). Additionally, biochemical and histopathological studies were conducted to assess the hepatotoxicity of the lead compounds. Insilico molecular properties and ADMET properties of the synthesized compounds were predicted using SwissADME and Deep-PK online tools to assess their drug-likeness. Among the tested compounds, 8b exhibited significant anti-mycobacterial activity with a minimum inhibitory concentration (MIC = 1 μg/mL) comparable to the reference drug ethambutol. Further, the compound demonstrated a binding affinity and orientation similar to the reference inhibitor 4PI, indicating its potential as a potent InhA inhibitor, and was found to be stabilized within the binding pocket of InhA through H-bonding, hydrophobic and van der Waal's interactions. Besides, the compounds hepatotoxicity assessment studies depicted that 8b showed no significant liver dysfunction or damage to liver tissues. Additionally, 8b adhered to Lipinski's rule of five and Veber's rule, displaying favourable pharmacokinetic and drug-like properties, including high human intestinal absorption, distribution, and acceptable metabolic stability and excretion. Compound 8b emerged as a promising candidate for further optimization and development as a therapeutic agent for tuberculosis, offering a new avenue for tackling tuberculosis.

A Recent Advance in the Diagnosis, Treatment, and Vaccine Development for Human Schistosomiasis.

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.

Associated Factors for Liver Fibrosis and Histological Activity Index in Treatment-Naïve HBeAg-Positive Chronic Hepatitis B Infection: Insights from a Retrospective Analysis.

The study aimed to identify predictors of advanced fibrosis score and histological activity index (HAI) in HBeAg-positive patients to facilitate early disease detection and reduce the need for invasive biopsies. The single-center retrospective study included treatment-naïve HBeAg-positive chronic hepatitis B (CHB) patients. Patients with HAI ≥6 and/or fibrosis ≥2 were considered to have significant liver damage. Independent determinants were identified by univariate and multivariate logistic regression analysis. Cut-off values for variables were determined by receiver operating characteristics (ROCs) curve analysis. The study enrolled a cohort of 66 patients, with 51.5% male and a median age of 26 (22.7-34.2) years. In assessing necroinflammation, no significant differences were observed in age and gender between patients with HAI <6 and HAI ≥6. However, patients with HAI ≥6 exhibited higher aspartate aminotransferase (AST) levels compared to those with HAI <6. Furthermore, lower albumin levels and platelet (PLT) counts, along with higher fibrosis-4 (FIB-4) scores, were associated with HAI ≥6. In the evaluation of fibrosis, while gender distribution did not differ significantly, patients with fibrosis grade ≥2 were older and had higher HAI scores, HAI ≥6 ratios, and FIB-4 scores compared to those with fibrosis grade <2. Multivariate analysis identified albumin as a significant predictor for both HAI ≥6 and fibrosis grade ≥2. The area under ROC (AUROC) values of albumin for predicting HAI ≥6 and fibrosis ≥2 were 0.696 and 0.698, respectively, indicating moderate predictive ability. Albumin was found to be an independent predictor of liver damage in HBeAg-positive CHB patients. The fact that the optimal threshold values detected for both HAI ≥6 and fibrosis ≥2 in this patient group were close to normal values suggests that clinicians should be more cautious in monitoring albumin levels and other pre-defined parameters to avoid delays in diagnosis.

Renal Manifestations of Chronic Hepatitis C: A Review.

Hepatitis C virus (HCV) has emerged as a major global health concern and, if left untreated, can lead to significant liver damage, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC). Approximately 40% of patients with HCV infection experience extrahepatic manifestations, including renal involvement. HCV-related renal disease is of significant importance among patients with chronic kidney disease (CKD), leading to higher morbidity and mortality. The renal damage due to HCV infection primarily results from cryoglobulinemia and glomerulonephritis, with conditions such as membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) being most prevalent. Despite advancements in treatment, including the use of directly acting antiviral agents (DAAs), renal complications remain a significant burden in untreated patients. HCV-positive patients on hemodialysis (HD) or those who have undergone kidney transplantation face increased mortality rates compared to their HCV-negative counterparts. Managing HCV infection before kidney transplantation is crucial to mitigate the risk of HCV-related renal complications. Conversely, kidney transplantation from HCV-infected donors is well established, as post-transplant treatment for HCV is safe and effective, potentially reducing mortality and morbidity for patients on transplant waiting lists. This review aims to provide a comprehensive analysis of the renal manifestations of HCV, emphasizing the importance of early diagnosis and treatment to improve patient outcomes.

Liver-specific Coxsackievirus and adenovirus receptor deletion develop metabolic dysfunction–associated fatty liver disease

Metabolic dysfunction–associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell–cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD.

Efficacy of DHA-enriched phosphatidylserine and its underlying mechanism in alleviating polystyrene nanoplastics-induced hepatotoxicity in mice

ObjectivePlastic pollution has become a global pollution problem that cannot be ignored. As the main destination of human oral intake, the toxic effects of plastic on the digestive system represented by the intestine and liver are the focus of current research. Marine-derived DHA-PS has a variety of biological activities, mainly focusing on improving brain function and regulating lipid metabolism. However, whether it has an improvement effect on PS-NPs-induced hepato-intestinal injury and the underlying mechanism remain unclear. MethodsA murine liver injury model was established by gavage of PS-NPs for six weeks. By integrating approaches from lipidomics, transcriptomics, and gut microbiota analysis, the molecular mechanism by which DHA-PS alleviates PS-NPs-induced murine hepatotoxicity was explored through the “gut-liver axis”. ResultsOur findings reveal that prolonged exposure to PS-NPs results in significant murine liver damage and dysfunction, characterized by increased oxidative stress and inflammation, along with exacerbated hepatic lipid accumulation. Mechanistically, PS-NPs disrupt the hepatic SIRT1-AMPK pathway by suppressing the expression of SIRT1, AMPKα, and PPARα, while enhancing the expression of SREBP-1c, ultimately leading to disordered hepatic lipid metabolism. The sphingolipid and glycerophospholipid metabolic pathways were particularly affected. Additionally, in agreement with transcriptomic analyses, PS-NPs activate the hepatic TLR4/NF-κB pathway. At the same time, exposure to PS-NPs decreases the expression of ZO-1, occludin, and claudin-1, diminishes the relative abundance of beneficial gut bacteria (norank_f_Muribaculaceae, Akkermansia, and norank_f_norank_o_Clostridia_UCG-014), and increases the prevalence of pathogenic gut bacteria (Coriobacteriaceae_UCG-002 and Desulfovibrio), exacerbating liver injury through the gut-liver axis. However, administering DHA-PS (50 mg/kg) effectively alleviated these injuries. ConclusionThis study was the first to employ multi-omics techniques to elucidate the potential mechanisms underlying hepatotoxicity induced by PS-NPs, thereby supporting the use of DHA-PS as a dietary supplement to mitigate the effects of nanoplastic pollutants.

MAPK signaling pathway induced LOX-1+ polymorphonuclear myeloid-derived suppressor cells in biliary atresia

Biliary atresia (BA) is a severe pediatric liver disease characterized by progressive bile duct destruction and fibrosis, leading to significant liver damage and frequently necessitating liver transplantation. This study elucidates the role of LOX-1+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in BA pathogenesis and assesses their potential as non-invasive early diagnostic biomarkers. Using flow cytometry, immunofluorescence, and molecular profiling, we analyzed the expression and activity of these cells in peripheral blood and liver tissues from BA patients and controls. Our findings reveal a significant increase in the frequencies and function of LOX-1+PMN-MDSCs in BA patients, along with MAPK signaling pathway upregulation, indicating their involvement in disease mechanisms. Additionally, the frequencies of LOX-1+PMN-MDSC in peripheral blood significantly positively correlate with liver function parameters in BA patients, demonstrating diagnostic performance comparable to traditional serum markers. These findings suggest that LOX-1+PMN-MDSCs contribute to the immunosuppressive environment in BA and could serve as potential diagnostic targets.

Effect of Vernonia Cinerea Water Extract on the Protection of Liver Tissue in Chronic Nicotine-Treated Rats

Nicotine, a highly toxic alkaloid found in tobacco, is known for its addictive properties and systemic side effects, including carcinogenic potential and multi-organ damage. Recent evidence indicates that nicotine can significantly impair liver function and regeneration by promoting fibrogenesis and oxidative stress. This study aimed to investigate the protective effects of Vernonia cinerea (VC) against nicotine-induced liver damage in Wistar rats, focusing on inflammation and pro-fibrosis markers. Thirty male Wistar rats were divided into three groups: a control group, a nicotine group (1 mg/kg/day), and a nicotine plus VC group (1 mg/kg/day nicotine and 100 mg/kg/day VC). Liver tissues were examined using Hematoxylin and Eosin staining, and Masson's trichrome staining to evaluate histological changes. Kupffer cell counts were determined using a Panoramic digital slide scanner. Statistical analyses were conducted to compare the groups. Nicotine exposure led to significant liver damage, characterized by increased inflammation, collagen deposition, and disruption of liver architecture. VC supplementation ameliorated these effects, reducing inflammation and fibrosis markers. Kupffer cell counts were lower in the nicotine plus VC group compared to the nicotine group alone. Conclusion: VC demonstrates a protective role in mitigating nicotine-induced liver damage, highlighting its potential as a therapeutic agent for preventing liver fibrosis and maintaining liver health in nicotine-exposed individuals.

Ethylene Glycol Poisoning with Acute Liver Injury Due to Delayed Diagnosis: An Autopsy Case Report and Literature Review

Ethylene glycol (EG), commonly used as antifreeze, is frequently ingested accidentally or in suicides, and causes acute renal failure. We report an unusual case of EG poisoning with acute liver injury. After vomiting and loss of consciousness, a 48-year-old male was admitted to the emergency room. Despite prompt conservative treatment for metabolic acidosis, kidney function deteriorated, necessitating the continuous renal replacement therapy. Blood toxicology results, showing EG levels of 510 mg/L, arrived 10 hours after admission. Oral ethyl alcohol therapy commenced 16 hours post-admission. By 36 hours, liver function tests indicated significant liver damage, and the patient died 45 hours upon admission. On autopsy, histological findings were hepatic centrilobular necrosis, cerebral perivascular neutrophilic and lymphocytic infiltration with calcium oxalate deposition, and renal tubular necrosis with calcium oxalate deposition. EG concentrations in the blood and gastric contents were 18.7 mg/L and 45.0 mg/L, respectively. Glycolic acid and oxalic acid, metabolites of EG produced by alcohol dehydrogenase in the liver, cause metabolic acidosis, renal tubular calcium oxalate deposition, and acute renal failure, leading to death. Generally, because fomepizole or ethyl alcohol block alcohol dehydrogenase in the liver, acute liver injury by EG poisoning is rare. To the best of authors’ knowledge, only one relevant report was found in the literature described a case in which EG caused centrilobular necrosis in liver. In the current case, delays in diagnosis and antidote therapy without gastric lavage allowed continued metabolism of EG which led to acute liver injury and acute renal failure.

The hepatoprotective potential of nigella sativa oil against cypermethrin-induced hepatotoxicity in rats: A histomorphological investigation.

Objective: To determine the hepatotoxic effects induced by cypermethrin. The study also attempts to evaluate the hepatoprotective efficacy of Nigella sativa oil against hepatotoxicity produced by cypermethrin. Study Design: Experimental study. Setting: Department of Anatomy, Pharmacology, and Pathology of Peshawar Medical College and Animal house of PCSIR Laboratories Complex, Peshawar. Period: May 2023 to Dec 2023. Methods: Animals were divided into two groups: Control (Group A) and Experimental (Group B). The Experimental group (Group B) is divided into two subgroups Group B-I and Group B-II. Forty-two male Sprague Dawley rats were randomly assigned to three groups of fourteen rats each in order to conduct an experimental investigation. Group A served as a control group. Cypermethrin (5.5mg/kg‾¹ body weight) per day dissolved in corn oil was administered orally to Group B-I. Cypermethrin (5.5 mg/kg‾¹ body weight) per day orally and (1ml/kg‾¹ body weight) per day of Nigella sativa oil were given to group B-II. Liver obtained from these groups were fixed for histological studies under light microscopy. Liver tissues of the cypermethrin-treated animals showed leucocytic infiltration, hydropic alterations such as ballooning degeneration and focal lytic (spotty) liver necrosis. Results: After four weeks of treatment with cypermethrin demonstrated significant liver damage in group B-I animals. In group B-II Nigella sativa oil significantly reduced hepatotoxicity and induced regenerative changes. Nigella sativa oil demonstrated protection against the cypermethrin and preserved the normal histological architecture of the liver. Conclusion: Cypermethrin had a hepatotoxic potential and caused hepatotoxicity in liver, as evidenced by the histological changes in the liver tissue. However, the study also found that Nigella sativa oil showed a better hepatoprotective effect, as it was able to effectively reverse the liver damage caused by both cypermethrin.

SIRT1-mediated tunnelling nanotubes may be a potential intervention target for arsenic-induced hepatocyte senescence and liver damage

Arsenic, a widespread environmental poison, can cause significant liver damage upon exposure. Mitochondria are the most sensitive organelles to external factors. Dysfunctional mitochondria play a crucial role in cellular senescence and liver damage. Tunnelling nanotubes (TNTs), membrane structures formed between cells, with fibrous actin (F-actin) serving as the scaffold, facilitate mitochondrial transfer between cells. Notably, TNTs mediate the delivery of healthy mitochondria to damaged cells, thereby mitigating cellular damage. Although limited studies have suggested that F-actin may be modulated by the longevity gene SIRT1, the association between arsenic-induced liver damage and this mechanism remains unexplored. The findings of the current study indicate that arsenic suppresses SIRT1 and F-actin in the rat liver and MIHA cells, impeding the formation of TNTs and mitochondrial transfer between MIHA cells, thereby playing a pivotal role in mitochondrial dysfunction, cellular senescence and liver damage induced by arsenic. Notably, increasing SIRT1 levels effectively mitigated liver mitochondrial dysfunction and cellular senescence triggered by arsenic, highlighting SIRT1's crucial regulatory function. This research provides novel insights into the mechanisms underlying arsenic-induced liver damage, paving the way for the development of targeted preventive and therapeutic drugs to address arsenic-induced liver damage.

Pathological and pharmacovigilance monitoring as toxicological imputations of azithromycin and its residues in broilers.

The importance of monitoring antimicrobial residues in food is underlined by increasing worries about food safety and public health. The potential toxicity of azithromycin (Az) on broilers and its impact on chicken meat residues require further investigation. This study assesses Az's toxicity effects and associated risks in broiler chickens through evaluation. One hundred and twenty chicks were distributed into four equal groups randomly. Each group received different daily oral doses of Az: 200 mg/kg for Az1, 100 mg/kg for Az2, and 50 mg/kg for Az3. The FAz group was given plain water. High-performance liquid chromatography was used to measure Az residue levels in muscle and liver. Oxidative markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT]), liver and kidney function tests, and histopathological examination were conducted. The levels of alanine aminotransferase and aspartate aminotransferase increased in Az1 and Az2 groups from 8 h to 3 days and decreased slightly in Az2 by 7 days, while they remained normal in Az3. The levels of uric acid and creatine in the Az1 and Az2 groups increased from 8 h to 3 days and subsequently decreased in Az2 by the 7th day. Az1 group showed the highest increase in MDA levels within 7 days. With higher Az doses, SOD and CAT levels showed a more significant decrease post-treatment. 9.1 μg/kg Az1 liver had the highest residues, whereas none were detected in muscle. At higher doses, Az caused significant liver and kidney damage, whereas lower doses had negligible effects. Muscle tissue contains fewer Az residues than liver. Assessing risks and ensuring compliance with regulations necessitate constant surveillance of Az residues in food. The health implications and risk management insights necessitate further investigation into the long-term effects of Az residues.

Optimization of methods for intrasplenic administration of human amniotic epithelial cells in order to perform safe and effective cell-based therapy for liver diseases

In animal experimental models the administration of stem cells into the spleen should ensure high effectiveness of their implantation in the liver due to a direct vascular connection between the two organs. The aim of this study was to update the methods of experimental intrasplenic cell transplantation using human amniotic epithelial cells (hAECs) which are promising cells in the treatment of liver diseases. BALB/c mice were administered intrasplenically with 0.5, 1, and 2 million hAECs by direct bolus injection (400 µl/min) and via a subcutaneous splenic port by fast (20 μl/min) and slow (10 μl/min) infusion. The port was prepared by translocating the spleen to the skin pocket. The spleen, liver, and lungs were collected at 3 h, 6 h, and 24 h after the administration of cells. The distribution of hAECs, histopathological changes in the organs, complete blood count, and biochemical markers of liver damage were assessed. It has been shown that the method of intrasplenic cell administration affects the degree of liver damage. The largest number of mice showing significant liver damage was observed after direct administration and the lowest after slow administration through a port. Liver damage increased with the number of administered cells, which, paradoxically, resulted in increased liver colonization efficiency. It was concluded that the administration of 1 × 106 hAECs by slow infusion via a subcutaneous splenic port reduces the incidence of complications at the expense of a slight decrease in the effectiveness of implantation of the transplanted cells in the liver.

Investigation of the Efficacy of Zonisamide in Alcohol Induced Hepatotoxicity

Subject: This research aims to evaluate the histological changes in liver tissue induced by alcohol consumption and to assess the effectiveness of zonisamide in treating alcohol-related hepatotoxicity. Materials and Methods: The study utilized 40 adult Wistar albino rats, divided into four groups: a control (sham), an ethanol group, a zonisamide group, and a combination of ethanol and zonisamide (ethanol+zonisamide). Each group underwent a four-day binge drinking protocol to mimic excessive alcohol intake observed in humans. Zonisamide was administered at a dose of 100 mg/kg daily. Post-treatment, the liver tissues were collected, stained with hematoxylin and eosin, and examined for histopathological changes. Results: The control and zonisamide-only groups showed no abnormal liver or vascular alterations, indicating zonisamide's safety. In contrast, the ethanol group displayed significant liver damage, including vascular dilatation, congestion, and extensive cellular degeneration. Conversely, the ethanol+zonisamide group exhibited substantial histological improvements with noticeable reductions in vascular impairments and signs of hepatocyte regeneration, suggesting that zonisamide mitigates the detrimental effects of alcohol on the liver. Conclusion: The study concludes that zonisamide has a protective effect against alcohol-induced liver damage. It appears to preserve the structural integrity of hepatocytes and supports cellular survival, potentially through its anti-inflammatory and antioxidant properties. These promising results advocate for further exploration of zonisamide as a therapeutic option for managing liver injuries associated with alcohol abuse. This study contributes significant insights into the therapeutic potential of zonisamide, encouraging more comprehensive investigations into its clinical applications in hepatology. Keywords: Alcohol, Zonisamide, Hepatotoxicity

Histopathological Changes Induced by Exposure of Mosquito Coil Smoke on the Liver of Adult Wistar Albino Rats – An Experimental Study

Background: Mosquito coils are widely used to control mosquitoes due to their low cost. However, their combustion releases harmful pollutants. Objective: This study investigates the histological changes in rat liver due to exposure to mosquito coil smoke containing d-trans allethrin. Methods: Eighteen Wistar rats were divided into three groups: control (Group A), exposed for 4 weeks (Group B), and exposed for 6 weeks (Group C). The rats were exposed to the smoke for 8 hours daily. Liver tissues were collected, fixed, sectioned, and stained for histological analysis. Results: Prolonged exposure to mosquito coil smoke leads to significant liver damage and inflammation due to the release of fine particles and toxic compounds. Conclusion: Long-term exposure to mosquito coil smoke is hepatotoxic. Public awareness and measures to minimize exposure are necessary.

Fasting potentiates diclofenac-induced liver injury via inductions of oxidative/endoplasmic reticulum stresses and apoptosis, and inhibition of autophagy by depleting hepatic glutathione in mice

Diclofenac, a widely used non-steroidal anti-inflammatory drug, can cause liver damage via its metabolic activation by hepatic CYP450s and UGT2B7. Fasting can affect drug-induced liver injury by modulating the hepatic metabolism, but its influence on diclofenac hepatotoxicity is unknown. Thus, we investigated diclofenac-induced liver damage after fasting in mice, and the cellular events were examined. Male ICR mice fasted for 16 h showed the elevation of CYP3A11, but the decreases of UGT2B7, glutathione (GSH), and GSH S-transferase-μ/-π levels in the livers. Diclofenac (200 mg/kg) injection into the mice after 16-h fasting caused more significant liver damage compared to that in the diclofenac-treated fed mice, as shown by the higher serum ALT and AST activities. Diclofenac-promoted hepatic oxidative stress (oxidized proteins, 4-hydroxynonenal, and malondialdehyde), endoplasmic reticulum (ER) stress (BiP, ATF6, and CHOP), and apoptosis (cleaved caspase-3 and cleaved PARP) were enhanced by fasting. Autophagic degradation was inhibited in the diclofenac-treated fasting mice compared to that of the corresponding fed mice. The results suggest that fasting can make the liver more susceptible to diclofenac toxicity by lowering GSH-mediated detoxification; increased oxidative/ER stresses and apoptosis and suppressed autophagic degradation may be the cellular mechanisms of the aggravated diclofenac hepatotoxicity under fasting conditions.

Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage

BackgroundThe timing of antiviral therapy for chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) or aged < 30 years is still undetermined. We aimed to elucidate the correlation between liver histology, age, and ALT level in CHB patients and analyze the histological characteristics of the liver among patients with persistently normal ALT or aged < 30 years.MethodsA retrospective analysis was conducted on 697 treatment-naive CHB patients. Liver biopsies were performed, and significant histological damage was defined as the grade of liver inflammation ≥ G2 and/or fibrosis ≥ S2 based on the Scheuer scoring system.ResultsThe liver inflammation grades and fibrosis stages correlated positively with age, ALT, AST, GGT levels and negatively with the counts of PLT (all p < 0.050) in HBeAg-positive patients. Higher ALT levels and lower PLT counts were independently associated with significant liver inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients. Furthermore, among those with persistently normal ALT levels, the incidence of significant liver inflammation and fibrosis were 66.1% and 53.7% in HBeAg-positive groups, and 63.0% and 55.5% in HBeAg-negative groups. Moreover, there was no significant difference in the prevalence of significant liver damage between patients aged < 30 years and those aged ≥ 30 years, in both HBeAg-positive (≥ G2 or ≥ S2: 63.8% vs. 75.8%, p = 0.276) and HBeAg-negative (≥ G2 or ≥ S2: 65.9% vs. 72.5%, p = 0.504) groups, among patients with persistently normal ALT levels.ConclusionsA considerable proportion of CHB patients with persistently normal ALT, including those below the age of 30 years, exhibited significant histological damage. This highlights the importance of initiating early antiviral therapy for HBV-infected individuals, even in the absence of elevated ALT levels.