Induced Liver Toxicity Research Articles

The M1/M2 Macrophage Polarization and Hepatoprotective Activity of Quercetin in Cyclophosphamide-Induced Experimental Liver Toxicity.

Chemotherapy drugs may lead to hepatic injury, which is considered one of the limitations of these drugs. The aim of this study was to evaluate the effect of quercetin (QUE) on M1/M2 macrophage polarization and hepatoprotective effect in cyclophosphamide (CTX)-induced liver toxicity. Twenty-four mice were divided into four groups (Control, QUE, CTX, CTX + QUE). The CTX and CTX + QUE groups received 200mg/kg CTX. The animals in the QUE and CTX + QUE groups received 50mg/kg QUE. All animals were sacrificed, and serum and liver samples were used for laboratory analyses. Examinations indicated that CTX exposure led to disruption of liver functions and morphological degenerations. Tissue pro-apoptotic Bax and caspase 3, pro-inflammatory TNF-α and IL-1β, transcription factor NF-κB, and M1 macrophage polarization marker CD86 were upregulated significant (p<0.05) in this group. In addition, CTX exposure led to significantly (p<0.05) upregulation of the Bax/Bcl-2 mRNA ratio and DNA fragmentations. The PCNA-positive hepatic cell ratio and anti-apoptotic Bcl-2 expression are remarkably suppressed (p<0.05). Immunohistochemical analyses are also indicated that M2 macrophage polarization marker CD163 is slightly but remarkably (p<0.05) downregulated in the CTX group compared to the Control and QUE groups. The morphological and biochemical disruptions were alleviated in QUE-treated animals in the CTX + QUE group. Liver function test results, apoptosis, inflammatory, transcription factor NF-κB, regeneration/proliferation, and apoptotic index results in this group were similar (p>0.05) to the control and QUE groups. The M1 cell surface marker expression of CD86 is significantly (p<0.05) downregulated, and M2 macrophage polarization marker expression of CD163 is upregulated significantly (p<0.05) compared to the CTX group. This study indicates that QUE has the potential to downregulate CTX-induced hepatic injury and regulate M1/M2 macrophage polarization to the M2 side, which indirectly demonstrates activation of anti-inflammatory signalling and tissue repair.

Investigating the role of Wnt3a and Wnt5a as critical factors of hepatic stellate cell activation in acute toxicant-induced liver injury

Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in liver regeneration during wound healing by secreting fibrogenic factors and production of extracellular matrix (ECM). However, repetitive injury to the liver can lead to extensive scarring and liver fibrosis, indicating HSCs coordinate both regeneration and disease. Because the factors contributing to HSC reprogramming during wound healing are not fully defined, we sought to further characterize morphogenic pathways of regeneration in an acute model of toxicant-induced liver injury1. Wnt/β-catenin signaling has been recently associated with progressive liver fibrosis, but its role in HSC reprogramming is not well defined. Here, we investigated the canonical role of Wnt3a/Wnt5a on β-catenin-dependent HSC transdifferentiation and find that hepatic ECM gene expression is increased and associated with Wnt3a, Wnt5a, and their transducers (Frizzled-2 and Frizzled-7) after an acute exposure of the hepatotoxin, carbon tetrachloride(CCl4). Moreover, we find exogenous Wnt3a and Wnt5a can accelerate spontaneous, culture-induced HSC activation in vitro as evidenced by increased total expression of fibrogenic factors, including Col1a1 and α-SMA. Challenge with Wnt3a induced canonical β-catenin-dependent transcription of axin2, which was attenuated by the Wnt coreceptor antagonist, Dickkopf-1 (DKK-1). These data support a role for canonical Wnt signaling as an additional mechanism by which HSCs dynamically respond to liver injury during the early wound healing response. New & noteworthy. This study elucidates novel mechanisms of fibrotic gene reprogramming in the liver. Specifically, we describe that Wnts and their transducers are increased during early liver injury which are associated with early fibrogenic responses and for the first time, causally link Wnts as direct inducers of HSC activation in the liver.Graphical abstract

Investigation of the protective effect of Lavandula stoechas against the damage caused by Bisphenol A in the liver tissue of rats

The present study aims to explore the hepatoprotective potential of Lavandula stoechas (LS) against Bisphenol A (BPA)-induced liver toxicity. In this experiment, 32 male rats were utilized and categorized into control, LS, BPA, and BPA + LS groups for the study. Each group received 50 mg/kg of the respective substance. Throughout the 28-day experiment, the control group did not receive any applications. The LS oil was administered intraperitoneally, while BPA was given through oral gavage. At the end of the experiment, rats were anesthetized, and blood was taken from the heart. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) values were measured from serum samples. Malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) measurements were performed in liver tissue. The histological structure was observed using hematoxylin and eosin staining methods. The BPA group showed higher AST levels compared to the control group, but the BPA + LS group exhibited a significant decrease in AST levels compared to the BPA group. Additionally, TB levels were lower in the BPA + LS group compared to the BPA group. MDA levels increased in BPA-treated groups compared to others. The LS-treated groups showed higher SOD levels compared to the control group. Furthermore, an evident increase was noted in the BPA + LS group in comparison to the BPA group. The BPA group exhibited a significant rise in OSI value compared to the control. It was concluded that LS has a protective impact against BPA-induced liver toxicity. The LS-treated groups showed higher SOD levels compared to the control group. Furthermore, a significant increase was noted in the BPA + LS group in comparison to the BPA group. The BPA group exhibited a significant rise in OSI value compared to the control. It was concluded that LS has a protective impact against BPA-induced liver toxicity.

1875P Real-world evidence of ribociclib induced liver toxicity in patients with breast cancer: A multi-center experience

1875P Real-world evidence of ribociclib induced liver toxicity in patients with breast cancer: A multi-center experience

Hesperetin alleviates aflatoxin B1 induced liver toxicity in mice: Modulating lipid peroxidation and ferritin autophagy

One of the ways Aflatoxin B1 damages the liver is through ferroptosis. Ferroptosis is characterized by the build-up of lipid peroxides and reactive oxygen species (ROS) due to an excess of iron. Dietary supplements have emerged as a promising strategy for treating ferroptosis in the liver. The flavonoid component hesperetin, which is mostly present in citrus fruits, has a number of pharmacological actions, such as those against liver fibrosis, cancer, and hyperglycemia. However, hesperetin's effects and mechanisms against hepatic ferroptosis are still unknown. In this study, 24 male C57BL/6 J mice were randomly assigned to CON, AFB1 (0.45 mg/kg/day), and AFB1+ hesperetin treatment groups (40 mg/kg/day). The results showed that hesperetin improved the structural damage of the mouse liver, down-regulated inflammatory factors (Cxcl1, Cxcl2, CD80, and F4/80), and alleviated liver fibrosis induced by aflatoxin B1. Hesperetin reduced hepatic lipid peroxidation induced by iron accumulation by up-regulating the levels of antioxidant enzymes (GPX4, GSH-Px, CAT, and T-AOC). It is worth noting that hesperetin not only improved lipid peroxidation but also maintained the dynamic balance of iron ions by reducing ferritin autophagy. Mechanistically, hesperetin's ability to regulate ferritin autophagy mostly depends on the PI3K/AKT/mTOR/ULK1 pathway. In AFB1-induced HepG2 cells, the addition of PI3K inhibitor (LY294002) and AKT inhibitor (Miransertib) confirmed that hesperetin regulated the PI3K/AKT/mTOR/ULK1 pathway to inhibit ferritin autophagy and reduced the degradation of ferritin in lysosomes. In summary, our results suggest that hesperetin not only regulates the antioxidant system but also inhibits AFB1-induced ferritin hyperautophagy, thereby reducing the accumulation of iron ions to mitigate lipid peroxidation. This work provides a fresh perspective on the mechanism behind hesperetin and AFB1-induced liver damage in mice.

Compound probiotics and glycyrrhizic acid alleviate DON-induced liver damage linked to the alteration of lipid metabolism in piglets

Compound probiotics are capable of effectively breaking down mycotoxins, and glycyrrhizic acid (GA) exhibits hepatoprotective properties. However, the protective efficacy and the underlying mechanism of combined intervention of GA and probiotics (GAP) on ameliorating Deoxynivalenol (DON)-induced liver toxicity remains unclear. This experiment involved 120 weaned piglets, encompassing the control group, the DON group, and the GPD group (E. faecalis and S. cerevisiae + GA + DON). Results showed that GAP significantly mitigated DON-related liver damage and oxidative stress. Furthermore, GAP inhibited the Nrf2/MAPK/NF-κB pathway, ultimately decreasing liver inflammation and apoptosis. Additionally, GAP significantly enhanced the expressions of ZO-1, GLUT2, PePT1, ASCT2, Occludin and Claudin-1. Moreover, metabolomics analysis revealed that GAP modulated lipid metabolism and mitigated liver damage by elevating serum levels of metabolites, such as phosphatidylcholine, phosphatidylethanolamine, and 3-amino-4-hydroxybenzoic acid. The research provides a theoretically based framework for using GAP to combat DON-induced hepatotoxicity in piglets.

Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats

ObjectiveThe hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. MethodsThirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Resultsα-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. ConclusionResveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.

Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats. Thirty-two rats (Rattus norvegicus) were divided into four groups including control, ATR (5 mg/kg), ATR (5 mg/kg) + SGN (10 mg/kg) and SGN (10 mg/kg) alone supplemented group. ATR exposure reduced the expression of Nrf-2 while instigating an upregulation in Keap-1 expression. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme‑oxygenase-1 (HO-1) and glutathione reductase (GSR) contents were decreased while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels after ATR treatment. Moreover, ATR poisoning increased the levels of ALT, AST, and ALP while reducing the levels of total proteins, and albumin in hepatic tissues of rats. Besides, ATR administration escalated the expressions of Bax and Caspase-3 while inducing a downregulation in the expressions of Bcl-2. Similarly, ATR intoxication increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, ATR disrupted the normal histology of hepatic tissues. However, SGN treatment remarkably protected the liver tissues via regulating antioxidant, anti, inflammatory, anti-apoptotic as well as histology parameters. Therefore, it is concluded that SGN can be used as therapeutic agent to combat ATR-induced hepatotoxicity.

Ameliorative Effect of Teucrium polium Extract against Nicotine Induced Liver Toxicity in Swiss Albino Mice

Background: Nicotine can be consumed in many forms, the most common of which is smoking tobacco. Tobacco smoking is a global problem that negatively affects human health. Natural plants are vital antioxidants that may antagonize the toxic effects of smoking. We designed the present study to assess the protective potential of Teucrium polium extract (TPE) on nicotine-induced liver toxicity in male mice. Methods: Twenty-four animals were allocated into four equal groups and daily treated for 21 constitutive days. Control group one received distilled water, group two orally received 100 mg/kg TPE, group three received subcutaneous injections of 2.5 mg/kg nicotine and group four received 100 mg/kg TPE orally then 2.5 mg/kg nicotine subcutaneously after one hour. Result: Nicotine exposure significantly elevated liver enzymes; alanine transaminase (ALT) and aspartate transaminase (AST). The levels of malondialdehyde (MDA) and nitric oxide (NO) were also elevated along with a reduction in glutathione reduced content (GSH), superoxide dismutase (SOD) and catalase (CAT) activity. Treatment with TPE considerably ameliorated the serum levels of liver enzymes, lowered MDA and NO levels, as well as elevated the antioxidant defense system. Also, TPE improved the histological structure and modulated apoptosis caused by nicotine. The current study proved the effectiveness of TPE as a natural antioxidant for the alleviation of nicotine-induced hepatic biochemical and histopathological alterations through attenuating oxidative stress, improving antioxidant systems and abrogating apoptosis.

A Pro-Drug Strategy Enhances Butyrate Bioavailability and Therapeutic Efficacy In Atherosclerosis

Abstract Butyrate is a gut microbiota derived short chain fatty acid with pleiotropic positive effects on inflammation and metabolism. In atherosclerosis, sodium butyrate has been shown to significantly reduce atherosclerotic lesions, rectify routine metabolic parameters such as LDL-C in the serum, and reduce systemic inflammation. However, its foul odor, low absorption, and fast metabolism limit its therapeutic effectiveness. We engineered a derivate of butyrate attached to the amino acid serine (SerBut) to mask the taste and odor and co-opt amino acid transporters in the gut to increase its bioavailability. In Vitro, SerBut maintains the anti-inflammatory, NFkB suppressing, capacity of sodium butyrate while allowing higher dosing without inducing cytotoxicity. SerBut can be stably, easily, and odorlessly administered in drinking water at higher doses than previously possible. Over 6 weeks of HFD in concurrence with SerBut water, SerBut reduces LDL-C in the serum, plaque accumulation in the aortic root, and monocytes in the aorta of an apolipoprotein-E-/- murine model of atherosclerosis. Bioinformatic analysis of fecal 16S rRNA sequencing reveals Seryl modification of butyrate to be associated with less plaque in the aortic root of mice, while general butyrate treatment was not. SerBut reduces enzymes associated with liver damage and has a systemic tolerogenic effect. SerBut is a promising therapeutic that lowers lipids and lipid driven inflammation without inducing liver toxicity.

Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team.

To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). The median follow-up period was 392days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n=22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5days, respectively; p=0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n=22 vs. n=3, respectively; p=0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

Effects of Buccholzia coriacea (wonderful kola) on hepatoprotective, nephrotective and oxidative stress of aluminium chloride induced wistar rats

Buchholzia coriacea seeds has been reported to have various medicinal properties. This study evaluates the effect of the aqueous extract of Buchholzia coriacea seed (wonderful kola), on Aluminium chloride induced liver toxicity in adult male Wistar rats. 24 rats weighing between 150 g - 210 g were divided into five groups. Group A- (the control group) received water and animal chow. Group B received 200mg/kg of AlCl3 only, Group C received aluminum chloride and vitamin C for 14 days. Group D received 250 mg/kg body weight body weight (Low Dose) of aqueous extract Buchholzia coriacea and (200 mg/kg) AlCl3. Group E received 1000mg/kg body weight (High Dose) of aqueous extract of Buchholziacoriacea and (250mg/kg) AlCl3. The animals were sacrificed, the liver and kidney was excised and processed for routine paraffin sections at 5micromes thick. Sections were stained with Haematoxylin and Eosin to demonstrate histoarchitecture. Biochemical analysis was also carried out to determine the effects on liver and kidney antioxidant enzymes. Histological assessment showed narrowed central vein, degeneration of hepatocytes and distortion of sinusoids in the AlCl3 alone treated groups. The histoarchitecture of the liver in the other groups showed improvement especially in Group E (High Dose of B. coriacea) and Group C (vitamin C and aluminum chloride only). The biochemical analysis on the other hand showed significantly reduced activities in GSH, SOD, CAT and significantly increased level of MDA in the AlCl3 only group. In the other groups, MDA levels reduced, GSH, SOD and CAT also increased enzymatic activities following the administration of B. coriacea. The study concludes that Buchholziacoriacea seed extract plays a role in protecting liver and kidney from AlCl3 toxicity.

Effect of Persea americana seed extract on 5-Fluorouracil Induced Hepatic Histotoxicity on Wistar Rats

This study evaluated the effect of Persea americana seed extract on 5-fluorouracil (5-FU) induced hepatic histoxicity in Wistar rats. A total of 77 Wistar rats were used in this study, 72 were treated intraperitonially with a single dose of 150mg/kg of 5-FU to induce liver toxicity and these animals were thereafter divided into six groups (2-7). The five (5) animals in group 1 which were not exposed to 5-FU served as control, Group 2 served as negative control, those in group 3 were administered with the medium dose of vitamin C at 500mg/kg while groups 4-6 received 250mg/kg, 500mg/kg and 1000 mg/kg of the extract respectively and those in group 7 received the medium dose of vitamin C and the extract orally. Each group from 2-7 had 12 animals, 3 animals were sacrificed from each group at weekly interval for 4 weeks and their blood and tissues were collected for biochemical and histological analysis. It was observed that the administration of 5-FU caused hepatic toxicity which was evidenced by histological alterations as well as increase in the levels of liver function parameters including Aspartate transaminase (AST), Alkaline phosphatase (ALP), Alanine transaminase (ALT). On the contrary, administration of the extract reversed the adverse effects caused by 5-FU.

Embryonic Amoxicillin Exposure Has Limited Impact on Liver Development but Increases Susceptibility to NAFLD in Zebrafish Larvae.

Amoxicillin is commonly used in clinical settings to target bacterial infection and is frequently prescribed during pregnancy. Investigations into its developmental toxicity and effects on disease susceptibility are not comprehensive. Our present study examined the effects of embryonic amoxicillin exposure on liver development and function, especially the effects on susceptibility to non-alcoholic fatty liver disease (NAFLD) using zebrafish as an animal model. We discovered that embryonic amoxicillin exposure did not compromise liver development, nor did it induce liver toxicity. However, co-treatment of amoxicillin and clavulanic acid diminished BESP expression, caused bile stasis and induced liver toxicity. Embryonic amoxicillin exposure resulted in elevated expression of lipid synthesis genes and exacerbated hepatic steatosis in a fructose-induced NAFLD model, indicating embryonic amoxicillin exposure increased susceptibility to NAFLD in zebrafish larvae. In summary, this research broadens our understanding of the risks of amoxicillin usage during pregnancy and provides evidence for the impact of embryonic amoxicillin exposure on disease susceptibility in offspring.

D-Tetramethrin causes zebrafish hepatotoxicity by inducing oxidative stress and inhibiting cell proliferation

d-Tetramethrin is one of the main components of mosquito control products, and is widely used for the control of dengue fever and insecticide production. Due to its widespread use, d-tetramethrin is a ubiquitous environmental pollutant and poses potential risks to human health. However, the effects of d-tetramethrin on liver morphology and function are not clearly established. In this study, we used zebrafish as an animal model to analyze the acute and chronic effects of d-tetramethrin exposure on the liver. We exposed zebrafish larvae and adults to different concentrations of d-tetramethrin and examined the impact of d-tetramethrin on lipid and glycogen metabolism, cellular properties, oxidative stress, cell proliferation, and apoptosis in the liver. We also analyzed transcriptional changes in genes related to apoptosis, inflammation, and cell proliferation using qPCR. Zebrafish exposed to d-tetramethrin exhibited severe liver damage, as evidenced by the presence of vacuoles and nuclear distortion in liver cells. The liver area in zebrafish larvae of the treatment group was significantly smaller than that of the control group. Significant lipid accumulation and decreased glycogen levels were observed in the livers of both zebrafish larvae and adults exposed to d-tetramethrin. Furthermore, d-tetramethrin exposure induced apoptosis and inflammation in zebrafish embryos. Additionally, d-tetramethrin caused liver damage, metabolic dysfunction, and impaired liver function. These results suggest that d-tetramethrin induces liver toxicity in zebrafish, by inducing oxidative stress and inhibiting cell proliferation.

Study of Role Flavonoid Compound Isolated from Camellia Sinensis (Black Tea) Extract against Methotrexate Drug Induced Liver Toxicity in Male Rate

Study of Role Flavonoid Compound Isolated from Camellia Sinensis (Black Tea) Extract against Methotrexate Drug Induced Liver Toxicity in Male Rate

Discovery of a synthetic taiwaniaquinoid with potent in vitro and in vivo antitumor activity against breast cancer cells

Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.

Methods to Study Liver Disease Using Zebrafish Larvae.

Liver disease affects millions of people worldwide, and the high morbidity and mortality is attributed in part to the paucity of treatment options. In many cases, liver injury self-resolves due to the remarkable regenerative capacity of the liver, but in cases when regeneration cannot compensate for the injury, inflammation and fibrosis occur, creating a setting forthe emergence of liver cancer. Whole animal models are crucial for deciphering the basic biological underpinnings of liver biology and pathology and, importantly, for developing and testing new treatments for liver disease before it progresses to a terminal state. The cellular components and functions of the zebrafish liver are highly similar to mammals, and zebrafish develop many diseases that are observed in humans, including toxicant-induced liver injury, fatty liver, fibrosis, and cancer. Therefore, the widespread use of zebrafish larvae for studying the mechanisms of these pathologies and for developing potential treatments necessitates the optimization of experimental approaches to assess liver disease in this model. Here, we describe protocols using staining methods, imaging, and gene expression analysis to assess liver injury, fibrosis, and preneoplastic changes in the liver of larval zebrafish.

Investigating the Preventive and Therapeutic Role of Costus afer in Acetaminophen Induced Liver Toxicity

The objective of this study was to determine the prophylatic and therapeutic role of Costus afer in acetaminophen poisoning in rats. The rats were equally divided into two groups; pre-treatment group and post-treatment group with each group have five sub-groups (negative control (NC), positive control (PC), A, B and C) of 5 rats each. NC was without any treatment; PC was treated with 800mg/kg of acetaminophen; A was treated with 200mg/kg of Costus afer; B was treated with 400mg/kg of Costus afer; C was treated with 800mg/kg of Costus afer. In the pre-treatment group, the PC was induced with acetaminophen 28 days after administration of distilled water, and “A”, “B” and “C” were induced with acetaminophen 28 days after Costus afer treatment while in the post-treatment group, the PC was induced with acetaminophen before commencing on 28 days administration of distilled water, and “A”, “B” and “C” were induced with acetaminophen before commencing on 28 days Costus afer treatment. After the treatment period, the rats were sacrificed and sample and liver organ were collected for laboratory analysis for liver enzymes and histological studies. The results showed that there was no significant change (p&gt;0.05) in liver enzymes in the A, B, C subgroups of the pre-treatment group after acetaminophen induction. In the post-treatment group, there was a significant decrease in the liver enzymes in A, B and C subgroups after Costus afer treatment. This study has proven that Costus afer has the potential to not only prevent acetaminophen liver toxicity but to also treat hepatotoxicity inflicted by acetaminophen in rats.

Tetrabromobisphenol a and its alternative tetrachlorobisphenol a induce oxidative stress, lipometabolism disturbance, and autophagy in the liver of male Pelophylax nigromaculatus

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) have been widely used as flame retardants. However, their potential health risks to organisms have raised concerns, particularly for liver toxicity. Present study aimed to explore the toxic effects of TCBPA and TBBPA on black-spotted frogs (Pelophylax nigromaculatus) liver oxidative stress, autophagy, and lipid accumulation. After exposure to 0.001, 0.01, 0.1, and 1 mg/L TBBPA and TCBPA for 14 days, the content of cholesterol and triglyceride were significantly elevated. In addition, the malondialdehyde level rose greatly in dose dependent. However, the glutathione level declined in high TBBPA groups (0.01 and 0.1 mg/L). Furthermore, expressions of Beclin1, Atg5, and Atg7 were significantly increased, while p62 was markedly declined, respectively. Results obstained suggested that TBBPA and TCBPA exposure induced liver toxicity in black-spotted frog. This study provided insights into the toxicity mechanism of bisphenol flame retardants in amphibians and will aid in the ecological risk assessment of flame retardants.