Novel microwave assisted carboxymethyl-graphene oxide and its hepatoprotective activity.

This study reports a novel, eco-friendly; fast and cost-effective microwave method for synthesizing carboxymethylated graphene oxide (CMGO) from sugarcane residues. Fourier-transform infrared spectroscopy (FTIR) confirmed successful CMGO synthesis through the presence of characteristic peaks at 1567.93 and 1639.29 cm-1 (COONa vibrations) and increased CH2 intensity compared to unmodified graphene oxide (GO). Furthermore, CMGO derived from sugarcane residues demonstrated potential in mitigating the side effects of toxic materials like carbon tetrachloride (CCl4). Treatment with CMGO partially reduced elevated levels of liver enzymes (ALT and AST) and nitrogenous waste products (urea and uric acid) in CCl4-induced liver damage models, suggesting an improvement in liver function despite ongoing cellular damage.This work paves the way for a sustainable and economical approach to produce functionalized graphene oxide with promising biomedical applications in alleviating toxin-induced liver injury.

The hepatoprotective potential of tannic acid against doxorubicin-induced hepatotoxicity: Insights into its antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models. Rats were randomly divided into four experimental groups: the untreated control, DOX, TA, and cotreatment (DOX + TA) groups. We investigated the antioxidant system's main components and oxidative stress indicators. Moreover, we examined alterations in the mRNA expression of critical regulators that modulate apoptosis, inflammation, and cell metabolism to better understand the underlying factors of DOX-induced liver toxicity. The results showed that DOX exposure caused an increase in MDA levels and a significant depletion of GSH content in rat liver tissues. Consistent with oxidative stress-related metabolites, DOX was found to significantly suppress both mRNA expression and enzyme activities of antioxidant system components. Moreover, DOX exposure had significant adverse effects on regulating the other regulatory genes studied. However, it was determined that TA could alleviate many of the negative changes caused by DOX. The results of the present study indicated that TA might be considered a versatile candidate that could prevent DOX-induced hepatotoxicity, possibly by preserving cell physiology, viability, and especially redox balance.

Mechanism of Action of Dihydroquercetin in the Prevention and Therapy of Experimental Liver Injury.

Liver disease is a global health problem that affects the well-being of tens of thousands of people. Dihydroquercetin (DHQ) is a flavonoid compound derived from various plants. Furthermore, DHQ has shown excellent activity in the prevention and treatment of liver injury, such as the inhibition of hepatocellular carcinoma cell proliferation after administration, the normalization of oxidative indices (like SOD, GSH) in this tissue, and the down-regulation of pro-inflammatory molecules (such as IL-6 and TNF-α). DHQ also exerts its therapeutic effects by affecting molecular pathways such as NF-κB and Nrf2. This paper discusses the latest research progress of DHQ in the treatment of various liver diseases (including viral liver injury, drug liver injury, alcoholic liver injury, non-alcoholic liver injury, fatty liver injury, and immune liver injury). It explores how to optimize the application of DHQ to improve its effectiveness in treating liver diseases, which is valuable for preparing potential therapeutic drugs for human liver diseases in conjunction with DHQ.

Ginsenoside RD prevents acute liver injury in mice by inhibiting STAT3-mediated NLRP3/GSDMD activation.

We investigated the role and mechanism of ginsenoside RD (GRD) in acute liver injury. Network pharmacology was used to analyze the correlations among GRD-liver injury-pyroptosis targets. A mouse model of acute liver injury was established by lipopolysaccharide + d-galactose（LPS + d/Gal). After pretreatment with GRD, the changes in mouse liver function were detected. The histopathological changes were assayed by hematoxylin and eosin and Masson staining, the tissue expressions of inflammatory cytokines were detected by enzyme-linked immunosorbent assay, and the protein expressions were assayed by immunohistochemical staining and Western blotting. Meanwhile, mechanism research was conducted using STAT3-knockout transgenic mice and STAT3-IN13, a STAT3 inhibitor. GRD inhibited liver injury, mitigated tissue inflammation, and suppressed STAT3-mediated pyroptosis in mice. After applying STAT3-knockout mouse model or STAT3-IN13, GRD did not further inhibit the liver injury. GRD can resist liver injury by inhibiting the STAT3-mediated pyroptosis, which is one of the hepatoprotective mechanisms of GRD.

Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats.

Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fasting blood glucose was measured. The rats were randomized into four groups: HC (healthy control; n = 7), T2DM (diabetic rats without treatment; n = 9), GLC (diabetic rats with 15 mg/kg gliclazide treatment; n = 7) and GLC+ALA (diabetic rats with gliclazide and 60 mg/kg ALA treatment; n = 7). T2DM was induced by a bolus administration of 110 mg/kg nicotinamide and 55 mg/kg streptozotocin intraperitoneally. The experimental protocol lasted for 6 weeks after which the animals were sacrificed and pancreas, liver and blood samples were collected for biochemical, histological and molecular analyses. Compared to healthy control (HC) group, exposure of HL-7702 cells to high glucose induced significant cell death by 19 % (p < 0.001), which was exacerbated with gliclazide treatment by 29 % (p < 0.0001) but markedly reduced by 6 % to near HC value following ALA treatment. In vivo, GLC-treated rats had severe liver damage characterized by increased hepatocellular vacuolation, and significant expression of ED-1, iNOS and caspase-3 as well as markedly high levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase compared to T2DM rats. Interestingly, ALA administration prevented these pathological changes and protected the diabetic liver to levels comparable to HC rats. ALA showed hepatoprotective effect against gliclazide-induced hepatotoxicity by suppressing inflammation and apoptosis while activating antioxidant pathway in the diabetic liver. Abbreviations: ALA, Alpha-lipoic acid; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; AMPK, Adenosine monophosphate-activated protein kinase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; DMEM, Dulbecco's Modified Eagle Medium; EDTA, ethylenediaminetetraacetic acid; FBG, Fasting blood glucose; FBS, Fetal bovine serum; GLC, Gliclazide; GLUT4, Glucose transporter type 4; GSH, Glutathione; H&E, Hematoxylin/Eosin; HbA1c, Glycosylated haemoglobin A1c; HC, Healthy control; HG, Hyperglycemic group; HOMA-ß, Homeostasis model assessment of ß-cell function; IL-1ß, Interleukin-1ß; IL-6, Interleukin-6; iNOS, Inducible nitric oxide synthase; KATP, ATP-dependent potassium channels; MDA, Malondialdehyde; MPTP, Mitochondrial permeability transition pore; NO, Nitric oxide; P/S, Penicillin/streptomycin; PAS, Periodic acid-Schiff; RIA, Radioimmunoassay; ROS, Reactive oxygen species; SOD, Superoxide dismutase; T2DM, Type 2 diabetes mellitus; TBARS, Thiobarbituric acid reactive substances; TNF-α, Tumor necrosis factor-alpha.

Inhibition of PLA2G4A attenuated valproic acid- induced lysosomal membrane permeabilization and restored impaired autophagic flux: Implications for hepatotoxicity.

Valproic acid (VPA) has broad efficacy against several seizures but causes liver injury limiting its prolonged clinical use. Some studies have demonstrated that VPA-induced hepatotoxicity is characterized by microvesicular hepatic steatosis. However, novel detailed mechanisms to explain VPA-induced hepatic steatosis and experimentally rigorously validated protective agents are still lacking. In this study, 8-week-old C57BL/6J mice were gavaged with VPA (500 mg/kg/d) for 4 weeks to establish an in vivo model of VPA-induced chronic liver injury. Quantitative proteomic and non-targeted lipidomic analyses were performed to explore the underlying mechanisms of VPA-induced hepatotoxicity. As a result, VPA-induced hepatotoxicity is associated with impaired autophagic flux, which is attributed to lysosomal dysfunction. Further studies revealed that VPA-induced lysosomal membrane permeabilization (LMP), allows soluble lysosomal enzymes to leak into the cytosol, which subsequently led to impaired lysosomal acidification. A lower abundance of glycerophospholipids and an increased abundance of lysophospholipids in liver tissues of mice in the VPA group strongly indicated that VPA-induced LMP may be mediated by the activation of phospholipase PLA2G4A. Metformin (Met) acted as a potential protective agent attenuating VPA-induced liver dysfunction and excessive lipid accumulation. Molecular docking and cellular thermal shift assays demonstrated that Met inhibited the activity of PLA2G4A by directly binding to it, thereby ameliorating VPA-induced LMP and autophagic flux impairment. In conclusion, this study highlights the therapeutic potential of targeting PLA2G4A-mediated lysosomal dysfunction in VPA-induced hepatotoxicity.

Linoleic Acid Alleviates Lipopolysaccharide Induced Acute Liver Injury via Activation of Nrf2.

Linoleic acid (LA) not only functions as an essential nutrient, but also profoundly modulates oxidative stress and inflammatory response. However, the potential mechanisms have not been adequately researched. Hence, this study examined the potential pharmacological roles of LA and the underlying mechanisms in mice with lipopolysaccharide (LPS)-associated acute liver injury (ALI). The results indicated that treatment with LA alleviated the histopathological abnormalities in the hepatic and plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutathione-S-transferase (GST) in mice with LPS exposure. In addition, LA inhibited the LPS-associated generation of proinflammatory factors, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and downregulated the hepatic myeloperoxidase (MPO) level. In addition, the administration of LA resulted in a reduction in hepatic malondialdehyde (MDA) levels and an elevation in liver superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and glutathione peroxidase (GSH-PX) levels. Further investigations revealed that LA promoted the expression of nuclear factor E2-related factor (Nrf2) and NAD(P)H: quinone oxidoreductase 1 (NQO1). In addition, the beneficial outcomes of LA on LPS-induced acute liver failure were revered when Nrf2 was pharmacologically suppressed by ML385. These experimental results demonstrated that LA supplementation attenuated LPS-associated acute hepatic impairment in mice via the activation of Nrf2.

Modulation of keap-1/Nrf2/HO-1 and NF-ĸb/caspase-3 signaling pathways by dihydromyricetin ameliorates sodium valproate-induced liver injury.

Nuclear factor erythroid factor 2 (Nrf2) is the key regulatory of the antioxidant response elements. Also, Nrf2 interacts with nuclear factor kappa B (NF-ĸB) to inhibit subsequent inflammatory cascade. Activation of Nrf2 signaling ameliorates drug-induced liver injury. Sodium valproate (SVP) is an anti-epilepsy drug with a hepatotoxic adverse effect that restricts its clinical use. In this study, coadministration of Dihydromyricetin (DHM), a natural flavonoid, with SVP to rats upregulated gene expression of Nrf2 and its downstream gene, heme oxygenase 1 (HO-1), while suppressed the Nrf2 repressor, Keap-1. Additionally, DHM led to downregulation of proinflammatory factors in liver tissues, including NF-ĸB, interleukin 1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α). This was accompanied by a decrease in the proapoptotic protein (cleaved caspase-3) expression level. Furthermore, biochemical and histopathological studies showed that DHM treatment improved liver function and lipid profile while decreased inflammatory cell infiltration, congestion, and hepatocellular damage. According to our knowledge, prior research has not examined the protective effect of DHM on the liver injury induced by SVP. Consequently, this study provides DHM as a promising herbal medication that, when used with SVP, can prevent its induced hepatotoxicity owing to its potential anti-oxidative, anti-inflammatory, and anti-apoptotic properties.

Examining the quaternary ammonium chitosan Schiff base-ZnO nanocomposite's potential as protective therapy for rats' cisplatin-induced hepatotoxicity.

BACKGROUND: Despite cisplatin's long history as a cornerstone in cancer therapy, both acquired chemoresistance and significant impacts on healthy tissues limit its use. Hepatotoxicity is one of its side effects. Adjunct therapies have shown promise in not only attenuating liver damage caused by cisplatin but also in enhancing the efficacy of chemotherapy. In this context, a new quaternary ammonium chitosan Schiff base (QACSB) was synthesized and applied as an encapsulating agent for the in-situ synthesis of QACSB-ZnO nanocomposite. MATERIAL AND METHODS: Thirty male albino rats were classified into Group 1 (control) distilled water, Group 2 (Cisplatin-treated) (12 mg/kg, i.p), and Group 3 (QACSB-ZnO NCs/cisplatin-treated) (150 mg/kg/day QACSB-ZnO NCs, i.p) for 14 days + a single dose of cisplatin. Liver functions, tissue TNF-α, MDA, and GSH were measured as well as histopathological and immunohistochemical studies were performed. RESULTS: The QACSB-ZnO NCs significantly restore liver functions, tissue TNF-α, MDA, and GSH levels (p < 0.001). Histopathological examination showed patchy necrosis in the cisplatin-treated group versus other groups. The QACSB-ZnO NCs showed a weak TGF-ß1 (score = 4) and a moderate Bcl-2 immunohistochemistry expression (score = 6) versus the CP group. CONCLUSIONS: QACSB-ZnO NCs have been shown to protect the liver from cisplatin-induced hepatotoxicity.

Liver injury protection of Artemisia stechmanniana besser through PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia stechmanniana Besser, one of the most prevalent botanical medicines in Chinese, has been traditionally used for hepatitis treatment. However, the bioactive components and pharmacological mechanism on alcohol-induced liver injury remains unclear. AIM OF THE STUDY: To investigate the effect of A. stechmanniana on alcohol-induced liver damage, and further explore its mechanism. MATERIALS AND METHODS: Phytochemical isolation and structural identification were used to determine the chemical constituents of A. stechmanniana. Then, the alcohol-induced liver damage animal and cell model were established to evaluate its hepato-protective potential. Network pharmacology, molecular docking and bioinformatics were integrated to explore the mechanism and then the prediction was further supported by experiments. Moreover, both compounds were subjected to ADMET prediction through relevant databases. RESULTS: 28 compounds were isolated from the most bioactive fraction, ethyl acetate extract A. stechmanniana, in which five compounds (abietic acid, oplopanone, oplodiol, hydroxydavanone, linoleic acid) could attenuate mice livers damage caused by alcohol intragastration, reduce the degree of oxidative stress, and serum AST and ALT, respectively. Furthermore, abietic acid and hydroxydavanone exhibited best protective effect against alcohol-stimulated L-O2 cells injury among five bioactive compounds. Network pharmacology and bioinformatics analysis suggested that abietic acid and hydroxydavanone exhibiting drug likeliness characteristics, were the principal active compounds acting on liver injury treatment, primarily impacting to cell proliferation, oxidative stress and inflammation-related PI3K-AKT signaling pathways. Both of them displayed strong binding energies with five target proteins (HRAS, HSP90AA1, AKT1, CDK2, NF-κB p65) via molecular docking. Western blotting results further supported the predication with up-regulation of protein expressions of CDK2, and down-regulation of HRAS, HSP90AA1, AKT1, NF-κB p65 by abietic acid and hydroxydavanone. CONCLUSION: Alcohol-induced liver injury protection by A. stechmanniana was verified in vivo and in vitro expanded its traditional use, and its two major bioactive compounds, abietic acid and hydroxydavanone exerted hepatoprotective effect through the regulation of PI3K-AKT signaling pathway.

Should high-dose N-acetylcysteine be given in cases of massive paracetamol overdoses: A narrative review.

N-acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20-21 h). The subject is further complicated because "massive overdoses" and "high-risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high-dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49-3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08-0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p = 0.043). There are no solid evidence to support that treatment with high-dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high-dose NAC regimen should be included in clinical practice.

Targeting SIRT1/AMPK/Nrf2/NF-кB by sitagliptin protects against oxidative stress-mediated ER stress and inflammation during ANIT-induced cholestatic liver injury.

Intrahepatic cholestasis is a common clinical form of hepatobiliary injury characterized by the intrahepatic accumulation of toxic bile acids. Besides its antidiabetic activity, the dipeptidyl peptidase IV inhibitor sitagliptin (SG) has been recently assigned diverse pharmacological activities and therapeutic potential against different disorders owing to its emerging antioxidant and anti-inflammatory properties. The current study explored the potential hepatoprotective effect of SG on α-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and investigate its possible targeted signaling pathways. Mice received SG (10 and 20 mg/kg) for four consecutive days, two days before and after a single oral administration of ANIT (75 mg/kg). Our results revealed that SG administration remarkably prevented ANIT-induced histopathological lesions in the liver and maintained hepatic functions and oxidative/antioxidant balance. Ultimately, SG counteracted the inflammatory response in the liver, as indicated by the marked suppression of hepatic expression of NF-κB, TNF-α, and IL-6. Moreover, it inhibited the endoplasmic reticulum (ER) stress response in the liver. These beneficial effects of SG were accompanied by upregulation of SIRT1, p-AMPK, and Nrf2 expressions while downregulating keap1 expression in the liver. In conclusion, this study is the first to demonstrate the ability of SG to protect against ANIT-induced CLI through modulating multiple signaling cascades, including SIRT1/AMPK, Nrf2/keap1, and NF-кB, which resulted in enhanced antioxidant capacity and repressed inflammatory and ER stress responses in the liver.

Assessment of high-dose acetylcysteine in acute high-risk paracetamol (acetaminophen) ingestion.

BACKGROUND: Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 µmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine. METHODS: Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 µmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L. RESULTS: We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067-42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25-9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89-8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant. DISCUSSION: Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data. CONCLUSIONS: Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion.

Christensenella minuta Alleviates Acetaminophen-Induced Hepatotoxicity by Regulating Phenylalanine Metabolism.

Acetaminophen (APAP)-induced liver injury (AILI), even liver failure, is a significant challenge due to the limited availability of therapeutic medicine. Christensenella minuta (C. minuta), as a probiotic therapy, has shown promising prospects in metabolism and inflammatory diseases. Our research aimed to examine the influence of C. minuta on AILI and explore the molecular pathways underlying it. We found that administration of C. minuta remarkably alleviated AILI in a mouse model, as evidenced by decreased levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and improvements in the histopathological features of liver sections. Additionally, there was a notable decrease in malondialdehyde (MDA), accompanied by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and superoxide dismutase (SOD) activity. Furthermore, there was a significant reduction in inflammatory markers (IL6, IL1ß, TNF-α). C. minuta regulated phenylalanine metabolism. No significant difference in intestinal permeability was observed in either the model group or the treatment group. High levels of phenylalanine aggravated liver damage, which may be linked to phenylalanine-induced dysbiosis and dysregulation in cytochrome P450 metabolism, sphingolipid metabolism, the PI3K-AKT pathway, and the Integrin pathway. Furthermore, C. minuta restored the diversity of the microbiota, modulated metabolic pathways and MAPK pathway. Overall, this research demonstrates that supplementing with C. minuta offers both preventive and remedial benefits against AILI by modulating the gut microbiota, phenylalanine metabolism, oxidative stress, and the MAPK pathway, with high phenylalanine supplementation being identified as a risk factor exacerbating liver injury.

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

OBJECTIVE: The 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. METHODS: Thirty-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). RESULTS: α-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. CONCLUSION: Resveratrol 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.

Protection against α-Amanitin-induced liver toxicity: Efficacy of pomegranate seed oil and black cumin oil.

The consumption of mushrooms containing α-Amanitin (α-A) can lead to severe liver damage. In this study, toxicological experiments were conducted to confirm the protective effects of pomegranate seed oil (PSO) and black cumin oil (BCO) against α-A-induced hepatotoxicity. Rats exposed once to α-A (3 mg/kg bw, i.p.) or saline alone (0.1 ml, i.p.) were either left untreated or treated with PSO or BCO at a dose of 2 ml/kg bw/day by oral gavage on the same day, and the treatment was continued for 7 days. Serum aminotransferases (ALT and AST), alkaline phosphatase (ALP) and total protein levels were measured and the active caspase 3 (cl-caspase 3) was evaluated by western blotting in the liver. Serum ALT, AST and ALP levels tended to decrease in the α-A exposed group, but no statistically significant difference was found compared to the saline group (p > 0.05). PSO and BCO did not affect serum liver function tests in rats exposed to saline or α-A. α-A toxicity was demonstrated by a significant decrease in serum total protein level (p < 0.05), a significant increase in liver cl-caspase 3 expression (p < 0.05), and structural liver damage mainly characterized by mononuclear inflammation and steatosis. When α-A exposed rats were treated with BCO, the increase in cl-caspase 3 was not inhibited, on the contrary BCO increased cl-caspase 3 in healthy rats (p < 0.05). PSO significantly ameliorated α-A-induced cl-caspase 3 increase and inflammatory histopathology in the liver. Both PSO and BCO completely prevented α-A-induced protein degradation. The findings indicate that PSO and BCO may protect liver functions against α-A-induced hepatotoxicity, encouraging future comprehensive studies to test them at different doses and frequency.

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Investigation of the effect of Myricetin on Cisplatin-induced liver hepatotoxicity.

OBJECTIVE: Cisplatin, a widely used anticancer agent, induces hepatotoxicity alongside organ damage. Understanding Cisplatin's toxicity mechanism and developing preventive measures are crucial. Our study explores Myricetin, a flavonoid, for its protective effects against Cisplatin-induced hepatotoxicity. METHODS: In our study, a total of 32 Wistar albino male rats were utilized, which were categorized into four distinct groups: Control, Myricetin, Cisplatin, and Myricetin+Cisplatin. For the histological assessment of hepatic tissues, hematoxylin-eosin and periodic acid Schiff staining were employed, alongside immunohistochemical measurements of TNF-α, interleukin-17, and interleukin-6 immunoreactivity. Additionally, aspartate transaminase and alanine transaminase values were examined by biochemical analysis. RESULTS: In the histological evaluation of the tissues, a normal healthy cell structure and a strong periodic acid Schiff (+) reaction were observed in the hepatocyte cells in the tissues of the Control and Myricetin groups, while intense eosinophilia, minimal vacuolization, congestion, and sinusoidal expansions were observed in the hematoxylin-eosin stainings, and a decrease in the positive reaction in the periodic acid Schiff staining was observed in the Cisplatin group. Consistent with these histological findings, an increase in TNF-α, interleukin-17, and interleukin-6 expressions (p<0.0001) and a concomitant increase in aspartate transaminase and alanine transaminase values were observed in the Cisplatin group. In the group protected by Myricetin, a significant improvement was observed in all these histological and biochemical values. CONCLUSION: Cisplatin induces notable histopathological alterations in the liver. In this context, Myricetin exhibits the potential to alleviate Cisplatin-induced damage by modulating histological parameters and biochemical processes.

Co-administration of either curcumin or resveratrol with cisplatin treatment decreases hepatotoxicity in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Background: Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Materials and Methods: Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Results: Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Conclusion: Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Phytolacca Dodecandra (L' Herit) (Phytolaccaceae) Methanol Root Extract Protects Liver from Acetaminophen-Induced Injury in Rats.

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury.