Liver Toxicity Research Articles

Short-term repeated oral intake of low dose cannabidiol: effects on liver enzyme activity and creatinine concentration during intense exercise.

The side effects and safety of cannabidiol (CBD) products are currently discussed in different contexts. Of all adverse effects, hepatotoxic effects have been reported most frequently in previous studies. However, the threshold for liver toxicity of CBD in humans is uncertain due to the lack of adequately designed studies in humans below the lowest observed adverse effect level (LOAEL) of 300 mg/day. In a randomised, three-arm, double-blind, crossover study, the effects of two CBD products (oil and solubilisate (solu) containing 60 mg CBD) were investigated during a high-intensity exercise protocol. Seventeen well-trained subjects (26±4 years, 181±5 cm, 85.6±9.4 kg) participated in the intervention. All subjects were healthy and had no physiological or psychological injuries. Participants were divided into advanced (Ad) and highly advanced (Hi) athletes … They consumed 60 mg of the compound in each microcycle over 7 days. To evaluate possible effects of short-term repeated use of 60 mg CBD on oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), gamma-glutamyl transferase (GGT) and creatinine (CREA) were analysed before and after each microcycle. GOT increased significantly in both performance levels of the placebo groups (Ad: p≤0.001; Hi: p=0.003). This increase was significantly reduced in the Ad group by both CBD oil (p=0.050, ES=0.66) and CBD solu (p=0.027; ES=0.75). GPT also increased significantly in both placebo groups (Ad: p≤0.001; Hi: p=0.032). This increase was significantly reduced in the Ad group by both CBD oil (p=0.027; ES=0.75) and CBD solu (p=0.023; ES=0.77). These effects were not observed in the Hi group for either parameter. Our results show that short-term repeated use of 60 mg CBD can inhibit exercise-induced liver activity. Furthermore, under the conditions of the present study, there was no evidence for hepatotoxic effects of oral intake of CBD at 60 mg for seven days. Nevertheless, despite the inhibitory effect on exercise-induced liver activity, the study provides evidence for the pharmacological effects of CBD on the liver even at low CBD dose and does not exclude adverse effects in sensitive individuals.

Could chronic opioid use be an additional risk of hepatic damage in patients with previous liver diseases, and what is the role of microbiome?

Summary: Among illicit drugs, addiction from opioids and synthetic opioids is soaring in an unparalleled manner with its unacceptable amount of deaths. Apart from these extreme consequences, the liver toxicity is another important aspect that should be highlighted. Accordingly, the chronic use of these substances, of which fentanyl is the most frequently consumed, represents an additional risk of liver damage in patients with underlying chronic liver disease. These observations are drawn from various preclinical and clinical studies present in literature. Several downstream molecular events have been proposed, but recent pieces of research strengthen the hypothesis that dysbiosis of the gut microbiota is a solid mechanism inducing and worsening liver damage by both alcohol and illicit drugs. In this scenario, the gut flora modification ascribed to non-alcoholic fatty liver disease performs an additive role. Interestingly enough, HBV and HCV infections impact gut–liver axis. In the end, the authors tried to solicit the attention of operators on this major healthcare problem.

Ultra‐High Performance Liquid Chromatography/Triple Quadrupole Ion‐Trap Mass Spectrometry‐Based Quantitative Assay of 17 Compounds to Unveil the Extraction Difference of Potentially Toxic Components Between the Single Drugs and Sishen Formula

ABSTRACTSishen formula is a famous prescription utilized to treat kidney diarrhea. The main components of Psoraleae Fructus and Euodiae Fructus are reported with the liver toxicity; however, the dissolution difference of those reported toxic compounds among the single medicine decoctions and those versatile compatibility forms has yet not been documented by quantitative assays. We established and validated an ultra‐high performance liquid chromatography/triple quadrupole‐linear ion‐trap mass spectrometry‐multiple reaction monitoring approach by targeting 17 components (e.g., four coumarins and eight flavonoids from Psoraleae Fructus; three alkaloids and two limonoids from Euodiae Fructus). Co‐decoction with Myristicae Semen or Schisandrae Chinensis Fructus could significantly affect the dissolution of coumarins and flavonoids from Psoraleae Fructus, whereas a weak influence was observed for combining Euodiae Fructus with Psoraleae Fructus. Combination with Schisandrae Chinensis Fructus could significantly increase the contents of both alkaloids and limonoids of Euodiae Fructus, but the effect of Myristicae Semen or Psoraleae Fructus was relatively slight. Moreover, the dissolution of Psoraleae Fructus coumarins and Euodiae Fructus limonoids in Sishen formula was remarkably inhibited, compared with the pure Psoraleae Fructus decoction, whereas the variation was weak between the Euodiae Fructus decoction and Sishen formula. These results benefit the bridge to the efficacy and toxicity changes of Sishen formula.

Long-term therapeutic efficacy and safety profiles of hpCas13d RNA editing in treating early-onset hypertrophic cardiomyopathy

AimsThrough evolving a precise RNA nuclease, hpCas13d, we have successfully inhibited hypertrophic cardiomyopathy in a compound heterozygous model. However, further investigation is needed to assess the long-term therapeutic effects and safety profiles of hpCas13d treatment. Materials and methodsAAV-hpCas13d[RQ] was subcutaneously injected into neonatal Myh6RH/RQ mice. Sequential echocardiography analyses were conducted at 4 months and 12 months to evaluate the sustained therapeutic effects of hpCas13d. Electrocardiography was employed to assess cardiac arrhythmias, and mice were euthanized at 12 months. Quantification of Myh6RQ degradation induced by hpCas13d[RQ] was performed using digital droplet PCR and cDNA sequencing. Histological analysis, RNA sequencing, and proteomic analyses were utilized to examine the inhibitory effects on pathological phenotypes and downstream signaling pathways. Biodistribution, tissue damage, and host immune response to AAV-hpCas13d[RQ] were assessed to evaluate long-term safety profiles. Key findingsThe allele-specific RNA degradation persisted for 12 months in AAV-hpCas13d[RQ]-treated Myh6RH/RQ mice. Partial degradation of pathogenic Myh6RQ transcripts proved adequate for the long-term inhibition of cardiac hypertrophy, arrhythmias, fibrosis, and cellular apoptosis in Myh6RH/RQ mice. RNA sequencing and proteomic analyses revealed that hpCas13d[RQ] treatment impeded hypertrophy and fibrosis, mitochondrial dysfunction, and abnormalities in ion channels downstream of mutant Myh6. Prolonged treatment with AAV-hpCas13d from the neonatal stage did not induce significant tissue damage, liver toxicity, humoral responses, or cellular immune reactions against the AAV9 capsid and bacterial hpCas13d. SignificanceThese results underscore the promising translational potential of AAV-hpCas13d in treating cardiovascular diseases and advancing in vivo gene therapy.

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

Sophoricoside reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling

Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from Sophora japonica. We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing in vitro experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.

Double-blind Randomized placebo-controlled Trials on controlling blood glucose level using the extract from <i>Opuntia ficus-indica</i> var. saboten

Objectives: The aim of this study was to evaluate the effects of Opuntia ficus-indica var. saboten extract on blood glucose regulation in both healthy individuals and those with impaired fasting glucose (IFG). Additionally, the study assessed the safety of <i>Opuntia</i> extract regarding liver and kidney function over a 12-week period.Methods: A double-blind, randomized, placebo-controlled clinical trial was conducted with 85 participants, including 47 healthy individuals and 38 individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IFG). Participants were randomly assigned to receive either Opuntia extract or a placebo for 12 weeks. Blood glucose control was evaluated using fasting blood glucose (FBS), oral glucose tolerance tests (OGTT), HbA1c, insulin, and C-peptide levels. Safety assessments included liver function tests (AST, ALT, <i>γ</i>-GTP, ALP) and kidney function tests (BUN, creatinine). Data were analyzed using independent and paired t-tests, with a significance level of p<0.05.Results: A total of 85 participants were initially enrolled, and after excluding 13 participants due to dropout, consent withdrawal, or protocol violations, the final statistical analysis was conducted with 72 participants. In the IFG group, Opuntia extract significantly reduced fasting blood glucose levels compared to the placebo group (p=0.010). Additionally, Opuntia extract reduced postprandial blood glucose levels at 120 minutes during the OGTT in healthy participants (p=0.047). No significant changes were observed in HbA1c, insulin, or C-peptide levels. Importantly, no adverse effects on liver or kidney function were detected in either group during the 12-week intervention.Conclusions: The administration of <i>Opuntia ficus-indica var. saboten</i> extract for 12 weeks demonstrated significant blood glucose-lowering effects in individuals with impaired glucose tolerance, without causing any liver or kidney toxicity. These findings suggest that <i>Opuntia</i> extract may be a safe and effective natural option for blood glucose regulation, particularly in pre-diabetic individuals. Further large-scale studies are recommended to confirm these results and explore its potential clinical applications.

Silver Nanoparticles and L-Cysteine Composite Redresses Carbon Tetrachloride-Induced Hepatotoxicity in Swiss Albino Rats.

l-cysteine is a versatile amino acid that plays a pivotal role in synthesizing critical molecules, enzymatic catalysis, regulation, and electron transport. It also has tremendous potential to act as an adjuvant for enhancing the biological efficacy of various nanoparticles in vivo. The current study is aimed to evaluate the protective efficacy of silver nanoparticles (AgNPs) decorated with l-cysteine in carbon tetrachloride (CCl4)-induced hepatotoxicity in the Swiss albino rats as an animal model. The rats were divided into four treatment groups: Group 1 (control without any treatments), Group 2 treated with AgNPs and l-cysteine composite (5 mg/kg body weight on every third day), Group 3 (single dose of 1 mL/kg CCl4), and Group 4 treated with AgNPs-l-cysteine composite in the rats pre-administered with CCl4. After treatment for a month, the rats were killed, and their liver and blood samples were subjected to biochemical analysis and histological examination.: Group 2 showed all the parameters comparable to control Group 1. On the contrary, CCl4-treated, Group 3 rats showed abnormally raised liver function markers (AST and ALT) and liver toxicity markers (GGT, LDH, and total bilirubin) concomitant with disturbed oxidative stress parameters (GSH and MDA) compared to the control. However, Group 4 rats demonstrated a significant recovery from CCl4-induced biochemical alteration in the animals as compared to Group 3. In addition, the biochemical measurements were harmonious with the histological analysis of the liver sections of the treated rats. Hence, the proposed AgNPs-l-cysteine composite is a potent hepato-protecting agent in vivo that can be employed in regulating CCl4-induced hepatotoxicity or any drug or potential pharmaceutical compound exerting similar toxicity.

Protective Effects of Silymarin Co-Administered with CCl4 on Hepatotoxicity and Its Impact on Liver enzymes and Lipid Profile

This study explained the protective effects of silymarin against liver toxicity induced by carbon tetrachloride (CCl4) in female rats. Silymarin, a natural herbal compound extracted from the Milk thistle (Silybum marianum) plant, possesses well-documented antioxidant, anti-inflammatory, and anti-fibrotic properties. In the conducted experiment, rats that received silymarin alongside CCl4 exhibited significant improvements in liver enzyme (ALT, AST, ALP, and GGT) levels and lipid profiles (Total Cholesterol (TC), Triglycerides (TG), Low-Density Lipoprotein (LDL), High-Density Lipoprotein (HDL), and Very Low-Density Lipoprotein (VLDL) compared to those treated only with CCl4. These findings indicate that silymarin may serve as a potential preventive option for reducing liver damage caused by CCl4. Additional research is needed to comprehensively understand silymarin's impact on lipid metabolism and liver injury.

Female rat liver after sub-acute dibutyl phthalate treatment: Histological, stereological, biochemical, and global gene expression study

Although it has been recognized that females are more susceptible to chemical-induced liver injury, the effects of dibutyl phthalate (DBP), a widely used synthetic chemical, on female liver structure and function are under-researched. Here, we sought to investigate the effects of DBP on histological, stereological, and biochemical parameters, as well as global gene expression in female rat liver. Female Wistar rats were exposed to 100, 500, and 5000 mg DBP/kg diet for 28 days, corresponding to 8.6, 41.43, and 447.33 mg DBP/kg body weight (B.W.)/day, respectively. The highest dose (447.33 mg DBP/kg B.W./day) was between the no-observed-adverse-effect level (NOAEL) and the lowest-observed-adverse-effect level for liver toxicity, whereas two lower doses (8.6 and 41.43 mg DBP/kg B.W./day) were below the NOAEL. Analysis of hematoxylin and eosin-stained sections revealed an increased volume of hepatocytes, their nuclei and cytoplasm, while the volume of sinusoids decreased in DBP-exposed groups compared to the control. Examination of Periodic acid-Schiff-stained sections showed reduced glycogen content, which was the most prominent in the highest dose group. Increased glutathione S-transferase and catalase activities, and decreased GSH content and superoxide dismutase activity were observed in DBP-exposed groups. The mRNA sequencing revealed DBP-induced dose-specific changes in various genes and biological functions in female rat liver. The highest number of deregulated genes was observed in the 500 mg DBP/kg diet group. In summary, exposure to DBP caused significant liver microstructural changes, decreased glycogen content, disturbed the redox status, and affected global gene expression in female rat liver.

Emerging Psychotropic Drug for the Treatment of Trigeminal Pain: Salvinorin A

Trigeminal neuralgia (TN) is chronic pain caused by damage to the somatosensorial system on the trigeminal nerve or its branches, which involves peripheral and central dysfunction pain pathways. Trigeminal pain triggers disruptive pain in regions of the face, including within and around the mouth. Besides clinical experiences, translating the language of suffering into scientific terminology presents substantial challenges. Due to the complex and multifactorial pathophysiology underlying trigeminal pain, elucidating its social impact presents significant difficulties. Carbamazepine and oxcarbazepine are first-line treatments for TN, achieving approximately 50% pain reduction in 60–70% of treated patients. However, their efficacy is often limited by common side effects, such as dizziness, vertigo, nausea, seizures, and cognitive symptoms. In some cases, patients experience severe side effects, including myelosuppression, hyponatremia, hormonal imbalances, liver toxicity, suicidal ideation, teratogenicity, and other adverse reactions. Given these clinical limitations, the search for new painkiller candidates continues. Hence, we focused this review on salvinorin A (SalA), a natural agonist of κ-opioid receptors (KORs), which demonstrated anti-nociceptive, anti-inflammatory, and anti-neuropathic properties in various experimental models of the spinal sensory system. Furthermore, preclinical evidence indicates that SalA does not induce dependence and demonstrates a favorable toxicological and safety profile in comparison with currently marketed opioid drugs. We propose Salvinorin A as a promising candidate for treating trigeminal neuralgia, offering the potential for reduced adverse effects.

Lutein protection against doxorubicin-induced liver damage in rats is associated with inhibition of oxido-inflammatory stress and modulation of Beclin-1/mTOR activities.

A wide range of clinical applications are reported for doxorubicin (DOX), yet both people and research animals experience substantial tissue damage. However, the protective mechanism of lutein, a natural carotenoid against doxorubicin associated liver toxicity has not been fully studied. Therefore, the aim of this study is to investigate the protective mechanism of lutein in doxorubicin-induced liver damage. Twenty male Wistar rats were randomly assigned to four groups and treated as follows: group 1 was administered 10-ml/kg body weight of normal saline intraperitoneally for a duration of 28days. Group 2 was administered doxorubicin (15-mg/kg body weight) intraperitoneally for 3days in a row. Group 3 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28days, and group 4 was administered intraperitoneal injections of lutein (40-mg/kg body weight) daily for 28days with last 3days in a row (days 26, 27, and 28) of doxorubicin injection (15-mg/kg body weight). Our results showed that lutein reduced levels of AST, ALT, ALP, LDH, MDA, nitrite, beclin-1, caspase-3, IL-6 as well as TNF-α against the increase caused by doxorubicin. GSH, SOD, GST, catalase, mTOR as well as Bcl-2 were markedly increased by lutein against the harmful effect of doxorubicin. Moreso, lutein restored normal histoarchitecture as well as reduced fibrosis. In conclusion, lutein protection against doxorubicin-induced liver damage in male Wistar rat is associated with inhibition of oxidative stress, pro-inflammatory reactions, and modulation of Beclin-1/mTOR activities.

Retraction Note: Hepatic ameliorative role of vitamin B17 against Ehrlich ascites carcinoma-induced liver toxicity.

Retraction Note: Hepatic ameliorative role of vitamin B17 against Ehrlich ascites carcinoma-induced liver toxicity.

In vitro assessment of the role of endoplasmic reticulum stress in sunitinib-induced liver and kidney toxicity

Sunitinib, a multi-targeted tyrosine kinase inhibitor, is prescribed for the treatment of metastatic gastrointestinal stromal tumors, advanced metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. Hepatotoxicity and nephrotoxicity are significant adverse effects of sunitinib administration; however, there is limited information regarding the molecular mechanisms of these adverse effects. The aim of the present study was to elucidate the role of endoplasmic reticulum stress in hepatotoxicity and nephrotoxicity induced by sunitinib. In addition to endoplasmic reticulum stress, oxidative stress and mitochondrial membrane potential were evaluated to investigate the molecular mechanism more comprehensively. Findings revealed that sunitinib exposure significantly increased the reactive oxygen species levels and decreased the Nrf2 gene expression and GSH/GSSG ratio, suggesting oxidative stress induction in normal hepatocyte (AML12) and normal kidney (HK-2) cell lines. Endoplasmic reticulum stress markers, including ATF4, CHOP, IRE1α, XBP1s and ATF6 mRNA expressions, were upregulated in AML12 cells. Furthermore, enhanced intracellular calcium levels also indicate endoplasmic reticulum stress in hepatocytes. In contrast, sunitinib exposure did not alter endoplasmic reticulum-related gene expression levels and intracellular calcium levels in HK-2 cells. In terms of mitochondrial membrane potential and caspase-3 activity, sunitinib induced mitochondrial membrane damage and increased caspase-3 activation not only in AML12 cells but also in HK-2 cells. The research findings indicate that sunitinib may induce cytotoxic effects in hepatocytes through mechanisms involving oxidative stress, endoplasmic reticulum stress, and mitochondrial damage. However, in the kidney, the toxicity mechanism is different from that of liver, and the endoplasmic reticulum stress does not seem to be involved in this mechanism.

A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction

Addressing drug-induced liver injury is crucial in drug development, often causing Phase III trial failures and market withdrawals. Traditional animal models fail to predict human liver toxicity accurately. Virtual twins of human organs present a promising solution. We introduce the Virtual Hepatic Lobule, a foundational element of the Living Liver, a multi-scale liver virtual twin. This model integrates blood flow dynamics and an acetaminophen-induced injury model to predict hepatocyte injury patterns specific to patients. By incorporating metabolic zonation, our predictions align with clinical zonal hepatotoxicity observations. This methodology advances the development of a human liver virtual twin, aiding in the prediction and validation of drug-induced liver injuries.

Clinical study of different interventional treatments for primary hepatocellular carcinoma based on propensity-score matching

BACKGROUND Transcatheter arterial chemoembolization (TACE) is the main treatment for patients with primary hepatocellular carcinoma (PHC) who miss the opportunity to undergo surgery. Conventional TACE (c-TACE) uses iodized oil as an embolic agent, which is easily washed by blood and affects its efficacy. Drug-eluting bead TACE (DEB-TACE) can sustainably release chemotherapeutic drugs and has a long embolization time. However, the clinical characteristics of patients before the two types of interventional therapies may differ, possibly affecting the conclusion. Only a few studies have compared these two interventions using propensity-score matching (PSM). AIM To analyze the clinical effects of DEB-TACE and c-TACE on patients with PHC based on PSM. METHODS Patients with PHC admitted to Dangyang People’s Hospital (March 2020 to March 2024) were retrospectively enrolled and categorized into groups A (DEB-TACE, n = 125) and B (c-TACE, n = 106). Sex, age, Child-Pugh grade, tumor-node-metastasis stage, and Eastern Cooperative Oncology Group score were selected for 1:1 PSM. Eighty-six patients each were included post-matching. Clinical efficacy, liver function indices (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin), tumor serum markers, and adverse reactions were compared between the groups. RESULTS The objective response and disease control rates were significantly higher in group A (80.23% and 97.67%, respectively) than in group B (60.47% and 87.21%, respectively) (P < 0.05). Post-treatment levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin were lower in group A than in group B (P < 0.05), whereas post-treatment levels of albumin in group A were comparable to those in group B (P > 0.05). Post-treatment levels of tumor serum markers were significantly lower in group A than in group B (P < 0.05). Patients in groups A and B had mild-to-moderate fever and vomiting symptoms, which improved with conservative treatment. The total incidence of adverse reactions was significantly higher in group B (22.09%) than in group A (6.97%) (P < 0.05). CONCLUSION DEB-TACE has obvious therapeutic effects on patients with PHC. It can improve liver function indices and tumor markers of patients without increasing the rate of liver toxicity or adverse reactions.

Pharmacotherapeutic potential of pratensein to avert metribuzin instigated hepatotoxicity via regulating TGF-β1, PI3K/Akt, Nrf-2/Keap-1 and NF-κB pathway

Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (Rattus norvegicus) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor–β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.

Optimizing selenium-enriched yeast supplementation in laying hens: Enhancing egg quality, selenium concentration in eggs, antioxidant defense, and liver health

This study evaluated the effects of selenium-enriched yeast (SY) supplementation at various levels on health and production parameters in laying hens, including egg production, egg quality, selenium (Se) concentrations in eggs, liver health, serum biochemical markers, antioxidant function, and immune responses. A total of 360 Hy-Line Brown hens (28 weeks old) were randomly assigned to four dietary groups with six replicates of 15 birds each, monitored over a 12-week feeding trial after a two-week acclimatization period. The dietary groups included a control (basal diet without selenium) and three SY-supplemented groups with Se levels of 0.3 mg/kg (SY03), 1.5 mg/kg (SY15), and 6.0 mg/kg (SY60). The results showed no significant effects of dietary SY on laying performance or feed efficiency (P > 0.05). However, the SY15 group showed significant improvements in egg quality, particularly in albumen height, Haugh Unit and yolk color (P < 0.05). Selenium concentrations in eggs, albumen, and yolk increased dose-dependently, with significant differences in the SY-supplemented groups (P < 0.001). Increased activities of liver enzymes including alanine transaminase, alkaline phosphatase, and aspartate transaminase, alongside elevated levels of uric acid were notable in the SY60 group (P < 0.05). In addition, histological analysis revealed significant hepatocyte degeneration and a higher liver organ index (P < 0.05), in the SY60 group. All of which suggests potential liver toxicity at higher selenium levels. Antioxidant capacity of the birds were significantly enhanced due to dietary supplementation of SY as indicated by increased serum levels of total antioxidant capacity, and activities of catalase, glutathione peroxidase, and superoxide dismutase (P < 0.05). Analysis of hepatic genes expression revealed that SY15 supplementation significantly upregulated key antioxidant-related genes (Nrf2, HO-1, CAT, and NQO1) and downregulated Keap1 expression (P < 0.05), suggesting strong activation of the antioxidant defense system. In conclusion, SY supplementation at 1.5 mg/kg improved egg quality, increased Se concentrations in eggs, and enhanced antioxidant capacity without affecting laying performance or liver health. This makes it a balanced approach to improving egg quality and poultry health. However, higher supplementation levels (6.0 mg/kg) resulted in liver damage, underscoring the importance of careful dosage consideration.

A pan-orthoebolavirus neutralizing antibody encoded by mRNA effectively prevents virus infection

Orthoebolavirus is a genus of hazardous pathogens that has caused over 30 outbreaks. However, currently approved therapies are limited in scope, as they are only effective against the Ebola virus and lack cross-protection against other orthoebolaviruses. Here, we demonstrate that a previously isolated human-derived antibody, 2G1, can recognize the glycoprotein (GP) of every orthoebolavirus species. The cryo-electron microscopy structure of 2G1 Fab in complex with the GPΔMucin trimer reveals that 2G1 binds a quaternary pocket formed by three subunits from two GP protomers. 2G1 recognizes highly conserved epitopes among filoviruses and achieves neutralization by blocking GP proteolysis. We designed an efficient mRNA module capable of producing test antibodies at expression levels exceeding 1500 ng/mL in vitro. The lipid nanoparticle (LNP)-encapsulated mRNA-2G1 exhibited potent neutralizing activities against the HIV-pseudotyped Ebola and Sudan viruses that were 19.8 and 12.5 times that of IgG format, respectively. In mice, the antibodies encoded by the mRNA-2G1-LNP peaked within 24 h, effectively blocking the invasion of pseudoviruses with no apparent liver toxicity. This study suggests that the 2G1 antibody and its mRNA formulation represent promising candidate interventions for orthoebolavirus disease, and it provides an efficient mRNA framework applicable to antibody-based therapies.

Inhibitory activity of nanoencapsulated quercetin against sodium arsenite-induced sub-acute liver toxicity in rats

Arsenic, a metalloid toxicant, is associated with a major global health problem as oxidative stress, a prime cause of tissue toxicity. The subject of our investigation was to assess the therapeutic efficiency of nanoencapsulated quercetin (QC) in combating sodium arsenite (NaAsO2)-inducted sub-acute hepatocellular toxicity in rat model. The rats of the hepatic damage group were injected subcutaneously (s.c.) four dosages of NaAsO2 (92.36 µM/kg b.wt.) twice a week. The rats of the polylactide nanoencapsulated QC group were injected intravenously (i.v.) four doses of nanoencapsulated QC (8.97 µmol/kg b.wt.) twice a week 2 h after the treatment (s.c.) with 92.36 µM /kg b. wt. NaAsO2 twice a week for four doses. The rats of the empty nanocasule or free QC treated group were injected i.v. four doses empty nanocapsule or free QC twice a week 2 h after the treatment (s.c.) with same doses of NaAsO2 twice a week for four doses. Arsenic deposition (580±20 µg/g protein) observed in liver tissue of rats treated with arsenite (92.36 µM/kg b.wt.), was found to reduce (120±9 µg/g protein) by the treatment of nanoencapsulated QC in rats significantly (p&lt;0.001). The levels of antioxidant enzymes and GSSG/GSH ratio enhanced (p&lt;0.001/0.1/0.01) by the treatment of NaAsO2 were reduced by the post treatment of nanoencapsulated QC significantly (p&lt;0.001/0.01). The levels of ROS, lipohydroperoxide or membrane microviscosity increased or decreased (p&lt;0.001) by the treatment of NaAsO2 were monitored to reduce or enhance significantly (p&lt;0.001) by the treatment of nanoencapsulated QC in rat liver respectively. The blood serum biochemical levels enhanced (p&lt;0.001) by the treatment of NaAsO2 were found to reduce significantly (p&lt;0.001) by the treatment of nanoencapsulated QC in rats. The TGFβ1 and MMP-13 in the rat plasma augmented (p&lt;0.001) by the treatment of NaAsO2-exposure were found to decline (p&lt;0.001) significantly by the treatment of nanoencapsulated QC in rats. The rats in the other groups such as empty nanocapsule or free QC treated showed no or less inhibitory efficiency against NaAsO2-treatment compared to nanoencapsulated QC treated group. Application of nanoencapsulated QC may be a potent formulation to get higher inhibitory therapeutic efficiency against NaAsO2-induced sub-acute hepatocellular toxicity.