Paracetamol-induced Hepatotoxicity Research Articles

Oxindole derivatives alleviate paracetamol-induced nephrotoxicity and hepatotoxicity: biochemical, histological, and computational expressions.

Oxindole is a nature-derived heteroaromatic nucleus with a history of preclinical uses in various conditions. In this study, oxindole derivatives, 6-chloro-3-(3-hydroxybenzylidene) indolin-2-one (3OH) and 6-chloro-3-(4-hydroxybenzylidene) indolin-2-one (4OH) were evaluated for nephroprotective and hepatoprotective effects. Paracetamol-induced nephrotoxicity and hepatotoxicity model was used in mice. Tissue histology and serum biochemistry were carried out to further support in vivo activity. Compound 3OH reduced serum urea and creatinine levels by 51.8% and 64.6%, respectively (p < 0.0001). Excretion of creatinine by 3OH 10mg was 52.8% as compared to silymarin. In case of urinary excretion of urea, the significant rise in excretion was observed in 4OH 15mg (30.4%; p < 0.05) and 3OH 10mg group (29.24%; p < 0.05). The compound 3OH exhibited restorative pattern of the renal tissues with slight inflammatory infiltrations. In case of hepatoprotective activity, 3OH reduced (59.9%; p < 0.0001) serum ALT at 5mg even more than silymarin and all other doses of oxindole derivatives. In case of serum AST, all treatment groups produced significant (p < 0.0001) reduction except 3OH 15mg.Computational studies supported the results as both derivatives were found to have promising interactions with enzymes at lower binding energies. Compound 3OH which possesses a hydroxyl group based on aromatic ring at meta position was the most successful drug candidate throughout this study. In a nutshell, the selected compounds elicited significant nephroprotective and hepatoprotective-like effects in mice.

Hepatoprotective Effect of Padina gymnospora in Albino Wistar Rat; A Biochemical and Histopathological Studies

The methanolic extract of brown algae, Padina gymnospora (PG) was tested for hepatoprotective properties against paracetamol (acetaminophen, APAP)-induced liver damage in male albino Wistar rat through in-vitro model. Liver is damaged by the variation of serum enzymatic and biochemical markers, such as serum glutamate oxaloacetate transaminase (SGOT or AST), serum glutamate pyruvate transaminase (SGPT or ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), bilirubin, albumin, and lipid peroxidation and antioxidant status were measured by SOD and SDH. The study found that PG caused dose-dependent histopathological changes in the liver and kidney of the rats. While low doses caused minimal alterations, higher doses resulted in significant tissue damage. This suggests that, despite its therapeutic potential, careful consideration is needed regarding dosage to ensure safety. Acute toxicity studies revealed that the LD50 value exceeded 3 g/kg body weight. These results indicate that the methanolic extract of PG contains active compounds with antioxidant, anti-inflammatory, detoxification support, liver regeneration, cholesterol regulation, prevention of liver fibrosis and hepatoprotective effects against high doses of paracetamol-induced hepatotoxicity [Fig. 1].

Paracetamol-induced hepatotoxicity after normal therapeutic doses in the Hong Kong Chinese population.

Paracetamol is generally safe at normal therapeutic doses of ≤4 g/day in adults. However, paracetamol-induced hepatotoxicity after normal therapeutic doses use has been reported. We investigated the epidemiology of this adverse drug reaction in the Hong Kong Chinese population. This territory-wide retrospective observational study included adult patients with suspected paracetamol-induced hepatotoxicity after normal therapeutic doses use from January 2011 to June 2022. We evaluated the demographic characteristics; paracetamol dose, duration, and reason for use; preexisting hepatotoxicity risk factors; laboratory findings; and their relationship with clinical outcomes. We identified 76 patients (median age: 74 years, 23 males) with suspected paracetamolinduced hepatotoxicity after normal therapeutic doses use. There were 14 cases with significant clinical outcomes (five deaths and nine cases of acute hepatic failure), with an incidence of 1.2 cases per year. For patients with significant clinical outcomes, they were significantly older (age >80 years), had a lower body weight (<50 kg), exposed to longer durations (>2 days) and higher daily doses (>3 g), and with higher proportion of malnutrition. Paracetamol-induced hepatotoxicity can occur at normal therapeutic doses in the Hong Kong Chinese population. The identified risk factors are consistent with international guidelines regarding susceptible patients. Considering the widespread local use of paracetamol and low incidence of severe hepatotoxicity, the current dosage recommendations are considered safe for the general population. For susceptible patients, a reduced maximum dose of ≤3 g/day is recommended, with liver function and serum paracetamol monitoring in place.

Exploring the phytochemicals, antioxidant properties, and hepatoprotective potential of Moricandia sinaica leaves against paracetamol-induced toxicity: Biological evaluations and in Silico insights.

Thirteen components were identified in the methanol extract of Moricandia sinaica leaves (MSLE) through analysis utilizing HPLC-ESI-MS/MS., including flavonoids, anthocyanins, phenolic acids, and fatty acids. The methanol extract of M. sinaica leaves contained total phenolics and flavonoids (59.37 ± 2.19 mg GAE/g and 38.94 ± 2.72 mg QE/g), respectively. Furthermore, it revealed in vitro antioxidant properties as determined by the DPPH and FRAP assays, with respective IC50 values of 10.22 ± 0.64 and 20.89 ± 1.25 μg/mL. The extract exhibited a notable hepatoprotective effect in rats who experienced paracetamol-induced hepatotoxicity. When a dose of 250 mg/kg was given, there was a 52% reduction in alanine transaminase and a 30% reduction in aspartate transaminase compared to the group with the disease. Furthermore, it demonstrated a 3.4-fold, 2.2-fold, and 2.6-fold increase in superoxide dismutase, non-protein sulfhydryl, and glutathione peroxidase, respectively. In addition, it demonstrated a 68% decrease in lipid peroxide levels compared to the group with paracetamol-induced condition. The verification was conducted using a histological study, which identified improved liver histology with a small number of distended hepatocytes. Moreover, in silico studies focused on the enzymes NADPH oxidase, butyrylcholinesterase, and tyrosinase as the targets for the major compounds. In conclusion, MSLE showed promising hepatoprotective and antioxidant activities due to its richness in antioxidant metabolites.

Investigating the Protective Effects of Ascorbic Acid Against Paracetamol-induced Liver Toxicity in Wistar Rats

Paracetamol is one of the most widely used analgesics and antipyretics but can cause severe liver damage at high doses. This study explores the potential protective effects of ascorbic acid (vitamin C) against paracetamol-induced hepatotoxicity in Wistar rats. For this experimental study, 25 mature male Wistar rats, weighing 140–180g, were divided into five groups: Group 1 stands for the Normal Control. Group 2 received 25 mg of PCM for 21 days, whereas Group 3 received 500 mg of ascorbic acid. Furthermore, after PCM was given, rats in groups 4 and 5 were given 500 mg and 1000 mg of ascorbic acid, respectively. Following PCM and Ascorbic acid treatment, biochemical parameters and histoarchitectural studies were examined. Histopathological examination of liver tissue was performed to evaluate cellular architecture and damage. Results indicated that treatment with ascorbic acid significantly mitigated the elevation of liver enzymes and histopathological changes compared to the paracetamol-only group. In conclusion, the research underscores the potential role of ascorbic acid in safeguarding liver function.

Hepatoprotective potential of coconut inflorescence sap against paracetamol induced toxicity in hep G2 cell lines

Coconut Inflorescence Sap (CIS) is the sweet, oyster-white colored, non-fermented juice obtained from the immature inflorescence of the Coconut tree. Acetaminophen (N-acetyl-p-aminophenol, or paracetamol) is one of the most frequently used drugs worldwide as an antipyretic or analgesic. HepG2 cell lines were used as an experimental model for studying in vitro hepatotoxicity induced by Paracetamol. The present study aims to identify biologically active compounds of CIS using LCMS analysis and to elucidate the ameliorative potential of CIS in alleviating paracetamol-induced hepatotoxicity. LC-MS analysis revealed the presence of 17 bioactive compounds. HepG2 cells were pretreated with Paracetamol (20 mM) for inducing toxicity, and Silymarin at a concentration of 50 μg/ml was used as a standard drug. The morphological analysis and MTT assay showed effective recovery from toxicity in cells treated with CIS in a dose-dependent manner. CIS at 25 μg/ml potentially showed the highest percentage of inhibitory activity against the toxicity induced by paracetamol. The treatment with paracetamol significantly increased the indicators of liver toxicity - LDH, SGOT, SGPT, and Glut.S Transferase in the media.CIS administration also increased the total protein levels, SOD, and Catalase activity. The morphological analysis, MTT assay, cytocompatibility studies, determination of enzymatic activities, etc., confirms the significant hepatoprotective efficacy of CIS.

The Antiulcer and Hepatoprotective Effects of Euphorbia hirta Petroleum Ether, Chloroform and Ethanolic Extracts on Paracetamol-induced Ulcerated Wistar Rats

Background: Hepatic and gastric diseases are two of the most common ailments in people. Numerous researches have been conducted to evaluate the effectiveness of herbal remedies in the treatment of hepatitis and stomach ulcers. Objective: The study aimed to determine the antiulcer and hepatoprotective activities of Euphorbia hirta petroleum ether, chloroform and ethanolic extracts on paracetamol-induced ulcerated Wistar rats. Materials and Methods: Euphorbia hirta was collected from the area of Salem, Tamil Nadu, India. The air-dried whole plant was crushed, and 500 g of the powder and petroleum ether, chloroform and ethanol were used for continuous extraction by the Soxhlet device. Phytochemical analysis of the extract was done by conventional and GC-MS analysis. Nine sets of six male Wistar rats, each weighing between 150 and 200 g, were used in this study. The standard control group, Group I, received only 1% v/v tween 80. Group II, negative control, received saline (1 ml/kg p.o.). Group III animals were given silymarin (200 mg/kg p.o.) and paracetamol (2 g/kg), which served as the standard of care. Animals in groups IV, V, VI, VII, VIII, and IX received two separate doses (200 and 400 mg/kg) of petroleum ether, chloroform, and ethanolic extracts of Euphorbia hirta L. Liver tissue was taken for histological investigation and placed in a 10% formalin solution. The liquid supernatant of liver cells was used to measure antioxidant parameters, such as catalase, superoxide dismutase, and LPO. Results: Phytochemical and GC-MS examination confirmed Euphorbia hirta extracts to have different biologically active phytoconstituents, like alkaloids, carbohydrates, glycosides, phenolic, flavonoids, tannin, sterols and alkaloids. Euphorbia hirta has been found to significantly protect against paracetamolinduced ulcer and hepatotoxicity compared to the negative control. A significant (p &lt; 0.001) reduction in SGPT, SGOT, ALP, DB and TB levels in the EEEH 400 mg/kg extract-treated group was observed compared to the paracetamol group. The PEEH extract exhibited no significant decrease in all biochemical parameters compared to the negative control. However, the standard drug showed a significant (p &lt; 0.001) decrease when compared to the negative control. SGPT, ALP, and DB levels demonstrated a significant (p &lt; 0.01) reduction with EEEH 200 mg/kg. The PEEH extract induced no significant decrease in all biochemical parameters compared to the negative control, and the chloroform extract of 200 mg/kg showed a less significant (p &lt; 0.05 &amp; p &lt; 0.01) difference compared to the negative control. The histopathology study confirmed EEEH 200 mg/kg to show good hepatoprotective activity. Conclusion: The findings have demonstrated Euphorbia hirta ethanolic extract to have effective antiulcer capabilities, and a decrease in LPO activity along with an increase in SOD, CAT, and LPO content have been observed, thereby leading to reduced oxidative stress. The antioxidant activity of Euphorbia hirta extract as a free radical scavenger and the hepatoprotective effect of the ethanolic extract have been indicated by the results of liver enzymes, DB and TB, and histology of liver tissue. More research is needed to recommend Euphorbia hirta as an effective supplement to treat paracetamol-induced ulcers and hepatotoxicity.

Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.

Mitigating of Paracetamol-induced Hepatotoxicity in Albino Mice Using Boerhaavia diffusa Extracts

Boerhaavia diffusa, renowned for its therapeutic efficacy in chronic liver diseases, operates through multifaceted mechanisms to uphold internal homeostasis. Its pivotal roles encompass modulation of intermediary metabolism of macromolecules, synthesis of crucial plasma proteins, enzymatic activities, and bile excretion.In this investigation, we aimed to evaluate the hepatoprotective potential of Boerhaavia diffusa against paracetamol-induced hepatotoxicity in rats. Our study revealed promising outcomes as the extracts obtained from Boerhaavia diffusa demonstrated a significant hepatoprotective role in albino rats subjected to hepatotoxicity induced by paracetamol administration. During the study, the animals were administered doses of 1g/kg b.wt and 2 g/kg b.wt of the plant extracts. Following paracetamol administration, conspicuous changes were observed in hepatocyte biochemical markers, indicative of hepatotoxicity. However, treatment with Boerhaavia diffusa extracts ameliorated these alterations, underscoring their potential to mitigate paracetamol-induced liver injury. These findings underscore the significant hepatoprotective properties inherent in the plant extracts derived from Boerhaavia diffusa. which can be utilized as a potential therapeutic avenue for the management of paracetamol-induced liver damage. These findings hold promise for the development of novel therapeutic interventions aimed at safeguarding liver health and mitigating the adverse effects of hepatotoxic insults.

Paracetamol overdose causing acute kidney injury without hepatotoxicity: a case report

BackgroundParacetamol is a widely used analgesic and antipyretic. Paracetamol-induced hepatotoxicity is well known, but nephrotoxicity without hepatotoxicity is rarely seen.Case presentationWe present a case of acute kidney injury without hepatotoxicity in paracetamol overdose. A 15-year-old girl was admitted 48 h after she had taken 10 g of paracetamol. She was complaining of abdominal pain and vomiting. Her blood level of creatinine was 1.20 mg/dL on admission, with a peak at 3.67 mg/dL 3 days later. The liver blood tests and blood paracetamol level were negative. She did not receive N-acetyl cysteine and was treated with intravenous fluid (crystalloid). The ultrasonography of the kidneys was normal. Her renal function returned almost to baseline 7 days after admission. It was concluded that the diagnosis was an acute kidney injury caused by acute tubular necrosis due to paracetamol overdose.ConclusionThis case shows that nephrotoxicity can occur without hepatotoxicity in paracetamol overdose.

Attenuation of paracetamol-induced hepatotoxicity in Ajuga bracteosa extract treated mice

Ajuga bracteosa (Ab) has tremendous medicinal value with long-established disease curing potential. The present study aimed to assess the hepatoprotective potential of Ab extracts in paracetamol-induced hepatotoxicity in mice. Group I (normal control) were treated with saline 1 ml/kg BW orally for 7 days while Group II (toxicant control) received saline 1 ml/kg BW for 6 days and Paracetamol (1000 mg/kg BW) on day7of the treatment. Group III received Standard drug silymarin (100 mg/kg BW) for 6 days and Paracetamol (1000 mg/kg BW) on day 7of treatment. Groups IV andV were administered with methanol extract (ME) 200 mg/kg BW and aqueous extract (AE) 1000 mg/kg BW for 6 days and Paracetamol (1000 mg/kg BW) on day 7th of the study. Both extracts showed hepatoprotective potential against the toxic effects of paracetamol, evidenced by serum analysis of biomarkers involved in liver injury and histopathological findings. Hepatotoxic mice pretreated with Ab plant extract or silymarin exhibited significant decrease in ALP, AST, and ALT enzyme level while GSH levels were markedly increased. According to histological observations, groups treated with PCM (toxicant control) showed significant necrosis and lymphocyte infiltration, while groups treated with silymarin and Ajuga bracteosa plant extract showed preservation of the normal liver structural features. The phytochemical analysis of ME and AE of Ab showed the presence of glycosides, phenolic compounds, tannins, fats, saponins, flavonoids, terpenes, oils, and fats. The antioxidant activity of these two extracts was determined by nitric oxide assay, DPPH assay, and ferric reducing power assay. The methanolic extract exhibited the highest antioxidant potential (78.09 ± 0.0806). The antioxidant potential of aqueous extract was 73.08 ± 0.248. The reducing power for methanolic extract and ascorbic acid (standard) 500 μg/ml was 0.933 and 0.987 respectively. The anti-inflammatory activity of both extracts was demonstrated by in vitro methods, namely albumin denaturation, proteinase inhibition, and membrane stabilization assays. The study suggests that Ab extracts have competence for attenuating inflammation, oxidants, and hepatotoxicity.

The ameliorative effect of methanol extract of Ricinodendron heudelotii (Baill.) leaves on paracetamol-induced hepatotoxicity in Wistar rats

Plants are a rich source of antioxidants that are produced naturally. Therefore, this study was aimed to evaluate the effect of the plant Ricinodendron heudelotii (Baill.) in the attenuation of paracetamol (PCM) hepatotoxicity in Wistar rats. Twenty-four male albino Wistar rats weighing between 200 and 250 g were divided into four groups, with six rats each. Group 1 served as the control group, receiving just distilled water. Groups 2 and 3 received orally 250 mg/kg bwt/day PCM and 300 mg/kg bwt/day methanol extract of Ricinodendron heudelotii (Baill.) leaves for two weeks, respectively. For group 4, the Ricinodendron heudelotii (Baill.) leaf extract was pre-administered for 1 week before receiving 300 mg/kg bwt/day Ricinodendron heudelotii (Baill.) leaves extract and 250 mg/kg bwt/day PCM for 2 weeks. As a marker of liver damage, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue reduced glutathione (GSH) concentration, superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase activities were utilized to determine antioxidant state, while malondialdehyde (MDA) concentration was employed as a lipid peroxidation indicator. When compared to the control group, the activities of serum AST, ALT, SOD, and MDA levels were considerably (p < 0.05) higher in the PCM group, although GSH level and GST and catalase activities were significantly lower. In comparison to the PCM group, co-administration of PCM with Ricinodendron heudelotii (Baill.) extract decreased serum AST and ALT activities. This study shows that the leaf extracts of Ricinodendron heudelotii (Baill.) protects Wistar rats’ livers from PCM-induced oxidative stress by increasing antioxidant enzymes.

Investigating the hepatoprotective properties of thymol against paracetamol-induced hepatotoxicity

The current research investigates thymol, a compound known for its antioxidant, antimicrobial, antifungal, antidiabetic, and analgesic properties, to assess its potential to protect the liver and determine how it might mitigate liver damage induced by paracetamol. For this study, the experimental animals were divided into five different groups, including a vehicle control group, a negative control group with paracetamol-induced liver damage, a positive control group treated with silymarin, and two groups treated with thymol in addition to paracetamol exposure. Liver function tests, histopathological analysis, and assessment of the activities of antioxidant enzymes were performed to assess the hepatoprotective effects of thymol treatment. Results revealed that treatment with thymol significantly restored the liver function markers to their normal values, including serum enzyme levels and lipid profiles, in paracetamol-induced liver damage. The histopathological examination demonstrated enhanced structural integrity of hepatocytes, decreased instances of necrotic cell death, and reduced infiltrated inflammatory cells in the groups treated with thymol. Furthermore, thymol treatment effectively increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) quantities in liver tissues. Overall, these results suggest that thymol has significant protective effects against paracetamol-induced liver toxicity through multiple mechanisms, including restoration of liver function, attenuation of oxidative stress, and preservation of hepatocyte integrity.

Unveiling the molecular basis of paracetamol-induced hepatotoxicity: Interaction of N-acetyl-p-benzoquinone imine with mitochondrial succinate dehydrogenase

Background and aimN-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. MethodMolecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. ResultThe molecular binding affinity score for APAP and NAPQI with SDH was predicted −6.5 and −6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. ConclusionThis study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.

Paracetamol-induced hepatotoxicity in a malnourished patient: A case report

Abstract Acetaminophen, an analgesic and antipyretic with a favorable safety profile, is used globally. However, excessive doses can lead to severe hepatotoxicity and acute liver failure. We present a case report that describes the unfortunate demise of a 48-year-old male patient with colon carcinoma who developed severe hepatotoxicity attributed to the administration of paracetamol following right radical hemicolectomy. Despite the patient receiving paracetamol at a dosage below the recommended limit under medical supervision, he experienced a rapid deterioration in liver function, leading to a cascade of life-threatening complications. The intricate interplay between medication administration and patient-specific factors emphasizes the ongoing need for the medical community to evolve and optimize treatment strategies for improved patient outcomes.

A Comparison of the Protective Effect of Pyridoxine and N-Acetylcysteine in Paracetamol Induced Hepatotoxicity in Rats

Paracetamol is a common over the counter drug. Paracetamol-induced hepatotoxicity results in over 300,000 hospitalizations each year and accounts for up to 42% of all cases of acute liver failure. N-acetylcysteine (NAC) is a potential antidote to manage paracetamol toxicity. Objective: To investigate the effects of pyridoxine, alone and in combination with NAC in repairing paracetamol-induced liver damage in male Wister rats. Methods: A single oral dose of paracetamol (650 mg/kg) was administered to Wistar rats to induce hepatotoxicity. The hepato-protective effects of NAC at a dose 300 mg/kg, and pyridoxine (200 mg/kg) were evaluated using standard liver function tests and histopathological along with serum glutathione levels. Results: The administration of pyridoxine and NAC resulted in a significant decrease in AST, ALT, and total bilirubin levels and the reversal of histopathological changes. Conversely, administering NAC and pyridoxine in combination yielded significant changes except for the glutathione level. Conclusions: The study concluded that pyridoxine may be used as a potential hepatoprotective drug in paracetamol-induced hepatotoxicity. In combination with NAC, it showed protective effects in paracetamol-induced hepatoxicity.

Counteracting Paracetamol-Induced Hepatotoxicity with Black Shallot Extract: An Animal Model Investigation

Counteracting Paracetamol-Induced Hepatotoxicity with Black Shallot Extract: An Animal Model Investigation

Hepatoprotective Effects of a Chemically-Characterized Extract from Cistus ladanifer: In Vivo and in Silico Investigations

Background: Liver damage is indicated by histopathological and metabolic dysfunction. There has been increasing interest in natural hepatoprotective agents from medicinal herbs. The medicinal plant Cistus ladanifer widely used in phytotherapy was selected for this study. Objectives: The work aims to investigate the hepatoprotective effects of Cistus ladanifer leaf extracts in vivo against the paracetamol-induced hepatotoxicity mice and in silico using the docking method. The chemical composition of the extracts was also studied. Materials and methods: The paracetamol-induced hepatotoxicity mice were treated with aqueous and methanolic extracts of Cistus ladanifer at two doses of 150 and 300 mg/kg body. The serum levels of aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, urea, and creatinine in mice-induced hepatotoxicity were measured to evaluate the hepatoprotective activity of the extracts. The histopathological alterations were also investigated. The chemical profile of methanolic and aqueous C. ladanifer extracts was determined using GC-MS. The Human Cytochrome P450 2E1(CYP2E1) was presented as a protein target and the docking was studied using Maestro version 11.5 software developed by Schrodinger, LLC. Results: The administration of C. ladanifer extracts showed hepatic protection at an oral dose of 150 and 300 mg/kg for the aqueous extract and only at 150 mg/kg for the methanolic one. The aqueous extract at both doses and the methanolic extract at 150 mg/kg didn’t occur any biochemical or histological alterations. However, the methanolic extract showed hepatic toxicity at 300 mg/kg. Various compounds were identified in the methanolic and the aqueous extracts, probably responsible of the hepatoprotective activity. The in silico study has also shown that some molecules present in both extracts presented a good affinity in the active site of Cytochrome P450 2E1 (CYP2E1). Conclusion: The results deserve more attention as C. ladanifer can be considered a source of pharmacological compounds with hepatoprotective effects. Further detailed investigation is needed to deepen the study.

Flaxseed Lignan Alleviates the Paracetamol-Induced Hepatotoxicity Associated with Regulation of Gut Microbiota and Serum Metabolome.

This study examined the protective effect of flaxseed lignans on liver damage caused by an overdose of paracetamol (PAM). The findings demonstrated that administering 800 mg/kg/d flaxseed lignan prior to PAM significantly decreased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBi) levels, while it increased liver superoxide dismutase (SOD) and glutathione (GSH) levels in mice. Flaxseed lignan renovated the gut microbiota dysbiosis induced by PAM by promoting the proliferation of sulfonolipid (SL) producing bacteria such as Alistipes and lignan-deglycosolating bacteria such as Ruminococcus while inhibiting the growth of opportunistic pathogen bacteria such as Acinetobacter and Clostridium. Furthermore, flaxseed lignan modulated the serum metabolomic profile after PAM administration, specifically in the taurine and hypotaurine metabolism, phenylalanine metabolism, and pyrimidine metabolism. The study identified eight potential biomarkers, including enterolactone, cervonyl carnitine, acutilobin, and PC (20:3(5Z, 8Z, 11Z)/20:0). Overall, the results suggest that flaxseed lignan can alleviate PAM-induced hepatotoxicity and may be beneficial in preventing drug-induced microbiome and metabolomic disorders.

Protective Effect of Black Seed and Lettuce Oils Against Paracetamol-Induced Hepatotoxicity in Rats.

&lt;b&gt;Background and Objective:&lt;/b&gt; The liver is one of the organs that play an essential role in the human body, including supporting metabolism, immune functions, digestive system, detoxification, storage of vitamins and other functions. This investigation aimed to study the protective effects of black seed and lettuce oil against hepatotoxicity as induced by paracetamol in experimental rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; Twenty male Sprague-Dawley albino rats weighing 150±5 g were divided randomly into four groups (5 rats each) and distributed as follows; 1st group was controlled negative (C -ve group), 2nd group controlled positive (orally administered with 500 mg/kg b.wt., paracetamol), 3rd and 4th groups were orally administered with black seed oil and lettuce oil at a dose of 1 mL/kg b.wt., each) as a preventive dose. All rats were sacrificed and blood was collected for biochemical analysis and then statistically analyzed. &lt;b&gt;Results:&lt;/b&gt; The rat administered with black seed and lettuce oils enhanced body weight gain, food intake and feed efficiency ratio. Moreover, exhibited a significant reduction in the liver enzymes AST, ALT, ALP and TBIL. Meanwhile, black seed and lettuce oils significantly improved kidney functions, lipid profiles and some immune biomarkers including creatine kinase (CK), Creatine Kinase-MB (CK-MB) and Lactate Dehydrogenase (LDH). &lt;b&gt;Conclusion:&lt;/b&gt; This study revealed that the oils of black seed (&lt;i&gt;Nigella sativa&lt;/i&gt;) and lettuce (&lt;i&gt;Lactuca sativa&lt;/i&gt;) have a protective role in improving body weight gain, food intake, feed efficiency ratio, liver enzymes, kidney functions, lipid profiles and some immune biomarkers against paracetamol-induced hepatotoxicity in experimental rats.