Paracetamol-induced Hepatotoxicity In Rats Research Articles

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

<b>Background and Objective:</b> 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. <b>Materials and Methods:</b> 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. <b>Results:</b> 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). <b>Conclusion:</b> This study revealed that the oils of black seed (<i>Nigella sativa</i>) and lettuce (<i>Lactuca sativa</i>) 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.

Ethanolic Extract of Citrus Sinensis Peel Markedly Mitigate Paracetamol-Induced Hepatotoxicity in Rats

Background: Herbal medicines have historically been crucial for enhancing human health. Previous studies have highlighted the antioxidant properties of various parts of Citrus sinensis. In light of widespread reliance on plant-based remedies, this study focuses on a particular herbal medicine, Citrus sinensis, known for its rich content of vitamin C, pectins, phenolic compounds, and flavonoids. Objective: This research aims to investigate the hepatoprotective potential of the ethanolic extract of Citrus sinensis peel in vivo, particularly focusing on its antioxidant capabilities. Methods: The study utilized biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and total proteins to assess the hepatoprotective action of the Citrus sinensis peel extract in serum of Wistar albino rats. The rats were divided into five groups, with varying treatments including a control group, a paracetamol-induced hepatotoxicity group, and groups receiving different doses of the Citrus sinensis extract. Results: Treatment with the ethanolic extract of Citrus sinensis peel at doses of 200 mg/kg and 400 mg/kg significantly mitigated the paracetamol-induced elevation of serum levels of AST, ALT, ALP, bilirubin, and total proteins. These improvements were comparable to those observed with the standard drug, silymarin. Conclusion: The study confirms the hepatoprotective effects of Citrus sinensis peel extract against paracetamol-induced liver damage. This protection was evident both biochemically and histopathologically, suggesting the potential therapeutic utility of Citrus sinensis in liver disorders.

The Hepatoprotective Effect of Omega-7 Against Paracetamol-Induced Hepatotoxicity in Male Rats

Abstract Paracetamol toxicity, whether accidental or not is a worldwide issue that leads to hepatotoxicity, acute liver failure, as well as irreversible liver injury requiring liver transplantation. Omega-7 is a monounsaturated fatty acid with a number of beneficial properties. The aim of the present study was to assess the potential protective role of omega-7 fatty acid against hepatotoxicity induced by paracetamol in male rats. Thirty male Rats were separated into five groups (six rats in each group) and received the following treatment: group 1 received liquid paraffin orally via gavage tube for seven days successively, group 2 received liquid paraffin orally via gavage tube for seven days successively, and on day eight, rats received a single intraperitoneal injection of paracetamol (500 mg/kg/day), group 3 received omega-7 (300 mg/kg/day) orally via gavage tube for seven days successively, group 4 received omega-7 (100 mg/kg/day) orally via gavage tube for seven days successively, and on day eight, rats received a single intraperitoneal injection of paracetamol (500 mg/kg/day), group 5 received omega-7 (300 mg/kg/day) orally via gavage tube for seven days successively, and on day eight, rats received a single intraperitoneal injection of paracetamol (500 mg/kg/day). On day nine, rats have been sacrificed by cervical dislocation and liver homogenate samples were collected for analysis. This study showed that there was a significant decrease in hepatic superoxide dismutase, catalase, glutathione-peroxidase and glutathione levels, accompanied with significant increase in hepatic malondialdehyde level in paracetamol group compared to the negative control group. However, administration of omega-7 resulted in significant increase in hepatic superoxide dismutase, catalase and glutathione levels and significant decrease in hepatic malondialdehyde level compared to paracetamol group. In conclusion, omega-7 has a protective effect on paracetamol-induced hepatotoxicity in rats. Keywords: Antioxidant, Hepatotoxicity, Omega-7, Oxidative stress, Paracetamol.

Antioxidative and Anti-Inflammatory Protective Effects of Fucoxanthin against Paracetamol-Induced Hepatotoxicity in Rats.

Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause hepatotoxicity and acute liver injury. The most common cause of drug-induced liver injury (DILI) in Saudi Arabia and worldwide is paracetamol overdose. Fucoxanthin (FUC) is an allenic carotenoid that is found in edible brown seaweeds, and it has antioxidant and anti-inflammatory effects. Several studies have shown the potential therapeutic effects of FUC in diabetes, cancers, and inflammatory disorders. This study aims to investigate the protective effect of FUC against PAC-induced acute liver injury in rats. FUC was administered (100, 200, and 500 mg/kg, p.o.) for 7 days, and then the liver injury was induced by the administration of PAC (2000 mg/kg, oral). Blood and liver tissue samples were collected from PAC-positive untreated, treated, and negative control rats. Biochemical and inflammatory parameters in the blood were measured. In addition, RT-PCR, Western blotting, and immunohistochemistry were performed for liver tissue. The serum levels of liver biomarkers (ALT, AST, and ALP) increased after PAC-induced liver toxicity; FUC-treated rats showed lower levels compared to the positive control. There was an increase in the expression of TNF-α, IL-1, IL-6, NF-kB, INF-γ, and iNOS and a decrease in IL-10, IL-22, and IL-10R expression after the FUC treatment of injured liver rats. For the hepatic inflammation and PAC-toxicity-induced oxidative stress genes and proteins, FUC-treated rats (100, 200, and 500 mg/kg) showed a reduction in the expression of oxidative stress genes. These results showed that FUC protected the liver against PAC-induced injury through antioxidant and anti-inflammatory actions. However, further clinical studies are required to confirm the findings.

Investigation of In-vivo antioxidant and hepatoprotective potential of ethanolic extracts of Bombax insigne (Sw.) K. Schum on Swiss albino Rat

Medicinal plants are frequently used in traditional medicine and about 80% peoples of developing countries use this traditional therapy to treat their ailments. Bombax insigne (Sw.). K. Shcum is a large deciduous tree, locally known as Bon or Pahari shimul or Tula gachh. The present study was designed to investigate the antioxidant and hepatoprotective potential of ethanolic extract of B. insigne fresh bark. In-vivo antioxidant activity tests were performed by determining the lipid peroxidation and catalase concentration of the homogenized liver of Swiss albino rats receiving two doses (1.5 and 3 gm/kg body weight) of the plant extract with 750 mg/kg body weight of paracetamol. For liver function tests (LFT), total 35 rats were taken and divided into five groups containing seven animals in each. Group I received distilled water; group II received only paracetamol. Group III received paracetamol with silymarin. Group IV and V both were treated with paracetamol along with two doses of B. insigne extract. To evaluate the hepatoprotective potential, seven liver test markers such as total protein, albumin, total bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) of rats were considered. Test’s result for antioxidant activity demonstrated that the plant extract could inhibit the level of lipid peroxidation (LPO) induced by paracetamol. Enhancement of the level of the antioxidant enzyme catalase (CAT) was also observed. Paracetamol-induced hepatotoxicity in rats, as judged by the raised total protein, albumin, total bilirubin, serum enzymes, ALT, AST, ALP, GGT, were significantly prevented by the treatment with the extracts at different doses, demonstrating the hepatoprotective action of B. insigne. Histopathological observation also confirmed the hepatoprotective potential of B. insigne. Livers those were challenged with paracetamol exhibits the dishevelment of normal hepatic cells with centrilobular necrosis, inflammatory encroachment of lymphocytes and fatty changes were significantly protected by plant extract. The results of the present study suggested that B. insigne has antioxidant and hepatoprotective potential.

Formulation and development of Oral herbal liquid dosage form with its quality evaluation parameters

The present work deals with the formulation and development of oral herbal liquid dosage and its comparative study with marketed dosage for quality evaluation parameters. We have used different Poly-herbs for the formulation of syrup because they expressed high effectiveness in a vast number of diseases. As aforementioned the therapeutic effect of herbal medicines is exerted due to the presence of different constituents and the effects are further potentiated when compatible herbals are formulated together in PHFs (Poly-herbal formulations). PHF show compatible effect with those of standard allopathic drugs. We had tested its Quality control pre and post-formulation evaluation parameters. The Quality control tests for developed herbal syrup include: Physical appearance (Color, Odor, and Taste), Clarity tests, solubility tests, pH, Density, Viscosity, Specific gravity, Refractive index, FTIR study of active constituent used in herbal syrup. This syrup is also tested for acute oral toxicity study (LD50), Antioxidant activity by using Nitric oxide free radical scavenging method, and hepato-protective activity by using paracetamol-induced hepatotoxicity in rats. From the obtained results, we concluded that formulated poly-herbal syrup passed all quality control tests and also proved its effectiveness. The formulation F2 and F3 were the best poly-herbal formulation and it was selected for further study. In hepato-protective activity, F2 formulation when compared with the standard formulation of silymarin have shown good results.

Role of cryopreserved placenta extract in prevention and treatment of paracetamol-induced hepatotoxicity in rats

Background/Aim: Drug-induced liver injury is one of the major causes of acute liver failure. Under current circumstances of the pandemic of COVID-19, the use of paracetamol which has a proven hepatotoxic effect has increased. This prompts the search for novel agents with hepatoprotective properties. The purpose of this article was to evaluate the hepatoprotective activity of cryoextract of the placenta (CEP) on the model of paracetamol-induced hepatitis. Methods: The study was performed on 28 male rats. Acute drug liver damage was modelled by intragastric administration of paracetamol twice at a dose of 1250 mg/kg. Results: The development of paracetamol-induced hepatitis in rats was accompanied by a 71.3 % increase (p < 0.001) in the content of active products of thiobarbituric acid (TBA-AP) in liver homogenates as compared with intact animals. Besides, there was a 2.1-fold (p < 0.001) increase of ALT activity, a 58.8 % increase (p < 0.001) of AST activity and a 4.2-fold (p < 0.001) increase of the concentration of total bilirubin as compared with intact rats. The use of cryopreserved placenta extract showed significant hepatoprotection in a rat model of paracetamol-induced hepatitis. This was demonstrated by a 2.3-fold (p < 0.01) increase of the antioxidant-prooxidant index, a significant (p < 0.001) decrease of activity of ALT (by 44.0 %) and AST (by 29.6 %), as well as by a decrease of direct bilirubin level by 52.5 % (p < 0.001) in animals treated with CEP as compared with rats without treatment. Conclusion: The development of acute paracetamol-induced hepatitis in rats was associated with activation of lipid peroxidation processes in liver tissues, while CEP showed marked hepatoprotective activity in paracetamol-induced hepatitis in rats.

Effects of <i>Sarcocephalus latifolius</i> Fruits Extract on Paracetamol-Induced Liver Damage in Wistar Rats

Background and Aim: Sarcocephalus latifolius is a medicinal plant commonly used in traditional medicine to treat various diseases. The aim of the present study is to evaluate the hepatoprotective activity of Sarcocephalus latifolius fruits aqueous extract against paracetamol-induced liver damage in rats. Material and Methods: Aqueous extract of Sarcocephalus latifolius fruits at doses of 100, 250 and 500 mg/kg were administered orally to rats with paracetamol-induced hepatotoxicity (1 g/kg). The treatment with the extract and paracetamol lasted 7 days. Silymarin (50 mg/kg) was given as reference control. All tested drugs were administered orally. Results: Our results show that the Sarcocephalus latifolius fruits extract induced a significant reduction (p Conclusion: Aqueous extract of Sarcocephalus latifolius fruits has hepatoprotective activity against paracetamol-induced hepatotoxicity in rats. But it would be important to evaluate the activity of aqueous extract of Sarcocephalus latifolius fruits on oxidative stress parameters in vivo in rats.

Assessment of Hepatoprotective and Antioxidant Activities of Ethanolic Extract of Tephrosia villosa in Albino Rats

<p style="text-align: justify;"><strong>Objectives: </strong>To Study the hepatoprotective and antioxidant activity of the whole plant, ethanolic extract of <em>Tephrosia villosa</em> (EETV). <strong>Methods: </strong>Hepatoprotective effect of EETV is studied against carbon tetrachloride (CCl₄) and paracetamol-induced hepatotoxicity in rats. Individual rats received EETV doses of 200 and 400 mg/kg (w/w) for seven days, respectively. On the 7^th day, induced hepatotoxicity in all rats of all groups by 1.25 ml/kg (i.p) CCl₄and paracetamol 1gm/kg/p.o. Determining effects of ETEV on antioxidant activity, SGOT, SGPT, ALP, and direct bilirubin were, and also performed a histopathological exam of the liver sections. Results: The extract prevented the exhaustion of glutathione and catalase levels and increased lipid peroxidation levels against CCl₄ induced and Paracetamol liver injury in rats. By histopathological evidence, EETV also significantly decreased biochemical levels of liver enzymes with high hepatoprotection at 200 mg/kg. <strong>Conclusion: </strong>Present study results strongly reveal that EETV has hepatoprotective and antioxidant activity against CCl₄ and paracetamolinduced hepatic impairment in experimental animals. <p style="text-align: justify;"><strong>Key words: </strong><em>Tephrosia villosa,</em> Hepatoprotective, Antioxidant, Carbon tetrachloride, Paracetamol, Silymarin.

Biofunctional significance of multi-herbal combination against paracetamol-induced hepatotoxicity in Wistar rats.

A multi-herbal combination (MHC) of five herbs, namely Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. was assessed against the paracetamol-induced acute hepatotoxicity in female Wistar rats. The animals were randomly assorted into seven groups with six animals in each group. The rats were pre-treated with MHC (50, 100, and 200 mg/kg bw) and silymarin (50 mg/kg bw) once daily for seven consecutive days via oral route followed by administration of paracetamol (3 g/kg bw) on day 7, an hour after the last administration of MHC and silymarin. It was observed that MHC administration significantly (p ≤ 0.05) overturned the paracetamol-induced increase in serum liver function biomarkers (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin), phase I reaction enzymes (NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), and oxidant biomarkers (lactate dehydrogenase, lipid peroxidation, lipid hydroperoxides, and protein content). MHC administration also reinstated the paracetamol-induced significant decrease (p ≤ 0.05) in haematological indices (haematocrit, haemoglobin, red and white blood cells, and platelets), phase II reaction enzymes (glutathione-S-transferase and DT-diaphorase), membrane-bound enzymes (Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase), and antioxidant biomarkers (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Overall, MHC at 200 mg/kg bw dose significantly (p ≤ 0.05) sheltered the red blood cells from the assault of free radicals, stabilized the structural and functional integrity of hepatocytes, hindered acetaminophen (APAP) biotransformation to its toxic metabolites, and endorsed conjugating abilities to detoxify toxic entities. Furthermore, MHC significantly (p ≤ 0.05) activated enzymatic machinery to scavenge/inhibit the formation of reactive oxygen species, regulated nucleic acid metabolism, surface potential, and membrane fluidity, attenuated tissue breakdown, quenched peroxyl radicals, and provided protection against tissue injury. The necroinflammatory scores revealed strong evidence of MHC (200 mg/kg bw) effectiveness against the paracetamol-induced hepatotoxicity in rats at p ≤ 0.05. The synergistic effect of major inherent phytoconstituents (kaempferol, ellagic acid, and gallic acid), detected by HPLC-PDA, in MHC might have overturned the paracetamol-induced biochemical toxic alterations in rat liver.

Protective effects of resveratrol and avocado oil against paracetamol-induced hepatotoxicity in rats

This study sought to assess the protective effects of resveratrol and avocado oil in relation to paracetamol-induced hepatotoxicity in rats. The rats were divided into five groups, namely the control, paracetamol (600 mg/kg), resveratrol (RES; 10 mg/kg) + paracetamol, avocado oil (AVO; 200 mg/kg) + paracetamol, and RES + AVO + paracetamol groups. The hepatoprotective activity was evaluated by measuring biochemical parameters such as the total antioxidant status (TAS) and the total oxidant status (TOS) in each rat’s liver homogenates. Any DNA damage was assessed by means of a comet assay. The results showed that the TOS levels were significantly increased in the paracetamol group when compared with the control group. The TOS levels were found to be significantly lower in the paracetamol groups, in comparison with the RES, AVO, and RES + AVO groups. Moreover, the TAS levels significantly increased in the RES and RES + AVO groups when compared with the paracetamol group. The histopathological examination revealed necrotic areas in the rats’ livers. Pretreatment with both RES and RES + AVO was found to reverse the oxidative stress parameters, DNA damage, and necrosis induced by paracetamol. These results suggest that a combination of REV and AVO may protect against paracetamol-induced hepatotoxicity due to their antioxidant properties.

Dibenzazepine combats acute liver injury in rats via amendments of Notch signaling and activation of autophagy.

Paracetamol is a commonly used over-the-counter analgesic and antipyretic drug. Nevertheless, an overdose of paracetamol leads to hepatic necrosis that can be lethal. This study aimed to assess the potential hepatoprotective effects of dibenzazepine, a Notch inhibitor, against acute liver injury in rats via interfering with oxidative stress, inflammation, apoptosis, autophagy, and Notch signaling. Silymarin (200 mg/kg, p.o.) or dibenzazepine (2 mg/kg, i.p.) were administered to rats for 5 days before a single hepatotoxic dose of paracetamol (800 mg/kg, i.p.). Pretreatment with silymarin and dibenzazepine significantly mitigated oxidative stress, inflammatory and apoptotic markers induced by paracetamol hepatotoxicity where dibenzazepine showed greater repression of inflammation. Furthermore, dibenzazepine was found to be significantly more efficacious than silymarin in inhibiting Notch signaling as represented by expression of Notch-1 and Hes-1. A significantly greater response was also demonstrated with dibenzazepine pretreatment with regard to the expression of autophagic proteins, Beclin-1 and LC-3. The aforementioned biochemical results were confirmed by histopathological examination. Autophagy and Notch signaling seem to play a significant role in protection provided by dibenzazepine for paracetamol-induced hepatotoxicity in rats, which could explain its superior results relative to silymarin. Graphical abstract.

Hepatoprotective effect of Omega-3 PUFAs against acute paracetamol-induced hepatic injury confirmed by FTIR.

Acute paracetamol over dose-induced hepatotoxicity is considered an important medical hazard especially among women. Omega-3 long-chain polyunsaturated fatty acids (Omega-3 PUFAs) daily doses are nowadays recommended for their antioxidant and anti-inflammatory potentials. Fourier transform infrared (FTIR) spectroscopy is considered a reliable method in analyzing cellular alterations and is now efficiently used to diagnose several diseases and the efficacy of drugs even in the early stages. The aim of our study was to evaluate the hepatoprotective effect of Omega-3 PUFAs against paracetamol-induced hepatotoxicity in rats confirmed through measuring protein alterations in hepatocytes by FTIR. Rats were pretreated with Omega-3 PUFAs (50 and 100 mg/kg) for 21 days prior to oral ingestion of paracetamol. FTIR results revealed that Omega-3 PUFAs (50 mg/kg) limited the toxic effects of paracetamol by restoring the hepatic amide I to amide II ratio. In addition; biochemical analyses demonstrated that serum ALT, AST, Cholesterol, LDL-cholesterol and Il-6 levels as well as hepatic TNF-α, MDA, NOx levels were decreased. Besides; serum HDL-cholesterol level and hepatic GSH level were increased. Histopathological examinations of hepatic sections validated the hepatoprotective potential. The overall effect of this dose was comparable to those of the usual recommended hepatoprotective supplement; silymarin. In conclusion; it would be recommended to use Omega-3 PUFAs in low doses on daily bases as a hepatoprotective agent.

Assessment of antioxidant traits and protective action of Egyptian acacia pods extracts against paracetamol-induced liver toxicity in rats.

This study investigates the protective effect of Egyptian acacia pod extracts against overdose of paracetamol-induced liver damage. Egyptian acacia green and brown pods were extracted by mixture of ethanol 80%: HCl (6M) (99:1 v/v). In extracts of green and brown pods, total phenolic content in hydrolyzed ethyl acetate fraction (HEF) at pH 4, was 649.89 and 712.14mg GAE/g while antioxidant activity was 95.55% and 97.35%, both being the highest than any fraction. HEF (pH 4) in brown pods was analyzed by HPLC, there were 22 phenolic compounds rich in ethyl vanillin about 227mg/g and 11 flavonoids rich in catechin 48.70mg/g. A biological experiment was conducted using HEF (pH4) in brown pods against overdose of paracetamol in albino rats induced to hepatotoxicity. Thirty rats were divided into five groups; a control group, a paracetamol group, and the other three received paracetamol plus silymarin or two doses of HEF. Animals were received paracetamol and treated with either silymarin or HEF showed reduced levels of liver (ALT, AST, and ALP) and kidney (urea, creatinine, and uric acid) markers compared with the control group as well as reduction of oxidative stress and increment antioxidant enzyme activity in liver tissue when compared with the paracetamol group. It could be concluded that both HEF and silymarin are considerably high hepatoprotector against paracetamol-induced hepatotoxicity in rats due to their strong antioxidant activity. PRACTICAL APPLICATIONS: Both HEF and silymarin improved liver functions and exerted strong antioxidant activities. This antioxidant activity would have a positive effect against oxidative liver damage caused by parcetamol. Thus, it may be concluded that the liver plasma membranes were protected and the regenerative and reparative capacity of liver by phenolic compound in HEF treatment. The study demonstrated the HEF hepatoprotective activity and recommends using Egyptian acacia pods for treatment of liver disorders.

Evaluation of the hepatoprotective activity of various extracts of Dyschoriste littoralis nees on paracetamol-induced hepatotoxicity rats

The current investigation was to examine the hepatoprotective potential of D.littoralis Nees. (family Acanthaceae) On paracetamol-induced hepatotoxicity in rats. The aerial parts of D.littoralis Nees. The powder was concentrated with various solvents (PE, EA, and methanol) through Soxhlet concentrates and different crude concentrates utilized for hepatoprotective activity. Hepatotoxicity was induced by paracetamol (2g/kg b.wt.) on the 5th day of the investigational period and given orally. Paracetamol-induced rats to exhibit elevated activities of liver enzymes such as SGOT, SGPT, ALP, gamma-glutamyltranspeptidase (GGT), creatinine, urea, total bilirubin, total cholesterol &amp; triglyc in serum. Furthermore, Oral administration of the ethyl acetate concentrates of D.littoralis (200 mg/ kgb.wt.) given rats were significant reduction the level of SGOT, SGPT, ALP, gamma-glutamyltranspeptidase (GGT) creatinine, urea, total bilirubin, total cholesterol &amp; triglycerides when compared to other concentrates. They also significantly elevated the concentration of complete protein and albumin when compared to other concentrates. Thus, results suggested that ethyl acetate concentrates of D.littoralis could afford better hepatoprotective activity against paracetamol-induced hepatotoxicity rats.

Study on lipid peroxidation and In vivo antioxidant activity of various extract of Dyschoriste littoralis nees on paracetamol-induced hepatotoxicity rats

The current investigation was to examine the antioxidant potential of D.littoralis Nees. (family Acanthaceae) On paracetamol-induced hepatotoxicity in rats. The aerial parts of D.littoralis Nees. The powder was concentratesed with various solvents (PE, EA, and methanol) through Soxhlet concentrates and various crude concentrates utilized for hepatoprotective activity. Hepatotoxicity was induced by paracetamol (2g/kg b.wt.) on the 5th day of the investigational period and given orally. Paracetamol-induced rats to exhibit elevated activities of TBARS and reduction the enzymes levels such as Superoxide dismutase(SOD), catalase(CAD), Glutathione peroxidise (GPx), Glutathione S transferase(GST) and Glutathione (GSH) in liver and kidney. Furthermore, Oral administration of the ethyl acetate concentrates of D.littoralis (200 mg/ kgb.wt.) given rats were major reduction the level of TBARS and also significantly elevated the levels of the enzyme such as Superoxide dismutase(SOD), catalase(CAD), Glutathione peroxidise(GPx), Glutathione S transferase(GST) and Glutathione (GSH) in liver and kidney as compared to other concentrates. Thus, results suggested that ethyl acetate concentrates of D.littoralis could be afford better antioxidant effect against paracetamol-induced hepatotoxicity rats.

MRI-based preclinical discovery of DILI: A lesson from paracetamol-induced hepatotoxicity

Worldwide, drug-induced liver injury (DILI) is a major cause of hepatic failure. It is also the leading cause of withdrawal, cautionary labeling, and restricted usage of licensed drugs; therefore, European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) warn that the existing methods of assessing DILI are insufficient and that some of the translational biomarkers of hepatotoxicity must be relooked. Magnetic resonance imaging (MRI) seems to be a proper tool in elucidating the effects of DILI in both preclinical and clinical studies, providing excellent visualization of the morphology of the liver parenchyma. Therefore, herein, we propose preclinical MRI assessment of liver injury in experimental paracetamol-treated rats. Quantitative MRI clearly provides evidence of adverse effects in the liver tissue caused by a single overdose of paracetamol (1 g kg−1 and 1.5 g kg−1 b.w.). The results of the MRI were confirmed by the histopathological examination (H&E) of the rat liver specimen, however the adverse effects were not disclosed due to standard aminotransferase assays (ALT/AST) in rat blood serum. The results of our analysis demonstrate the successful application of MRI in the examination of paracetamol-induced hepatotoxicity in rats; it has a potential to serve as the early diagnostic tool for the prediction of DILI in preclinical evaluation.

Evaluation of Hepatoprotective Activity of Zanthoxylum armatum on Paracetamol-induced Liver Toxicity in Rats

The present study was carried out to identify phytochemical compounds and to study the hepatoprotective activity of Zanthoxylum armatum rhizome. Phytochemical analysis was carried out using standard procedures to quantify total alkaloid and phenolic contents. Hepatoprotective activity was determined using paracetamol-induced hepatotoxicity in rats. Zanthoxylum armatum extracts showed the presence of steroids, terpenoids, flavonoids, alkaloids, glycosides, phenols, oils, tannins and carbohydrates. The methanol extract has more phenolic and alkaloid contents than other extracts. The methanol extract at 500 mg/kg showed greater hepatoprotective activity with 66.87, 64.84, 67.95, 60.76 and 65.85 % protection on aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin and total protein enzyme levels of the liver, respectively. The results of the present study and previous reports indicated that phytochemical constituents variety in Zanthoxylum armatum and its' extracts possessed antioxidant, antibacterial and hepatoprotective activity.

PROTECTIVE EFFECT OF ACORUS CALAMUS RHIZOME IN PARACETAMOL EXPOSURE INDUCED HEPATOTOXICITY IN RATS: BIOCHEMICAL AND HISTOPATHOLOGICAL STUDY

Objective: To study the hepatoprotective activity of an aqueous and alcoholic extract of Acorus calamus rhizomes against the paracetamol induced hepatotoxicity in rats.Methods: Hepatotoxicity was induced by oral administration of paracetamol and chemical parameters such as Glutathione peroxidase, Glutathione reductase, Glutathione, Catalase, lipid peroxidation and histopathological changes in liver was studied by comparing with Silymarin, a standard hepatoprotective drug.Results: Treatment of rats with aqueous and alcoholic extract of Acoruscalamus rhizome after paracetamol administration normalized the altered levels of above parameters which may comparable with Silymarin and Vit-E. The hepatoprotective activity was confirmed by histopathological examination of the liver tissue of control and treated animals.Conclusion: Based on the result it can be concluded that Acorus calamus rhizome possesses hepatoprotective effect against paracetamol-induced hepatotoxicity in rats.

Protective effect of an L-type calcium channel blocker, amlodipine, on paracetamol-induced hepatotoxicity in rats.

Paracetamol (P), one of the most popular and commonly used analgesic and antipyretic agents, causes hepatotoxicity in overdoses. Amlodipine (AML), an L-type calcium channel blocker, has been shown to have anti-inflammatory activity by reversing the effect of calcium in the inflammation pathogenesis. In this study, the hepatoprotective activity of AML on P-induced hepatotoxicity was evaluated. Thirty male albino Wistar rats were divided into five groups: (1) control, (2) 2 g/kg of P, (3) 2 g/kg of P + 5 mg/kg of AML, (4) 2 g/kg of P + 10 mg/kg of AML, and (5) 10 mg/kg of AML. Some liver enzymes, oxidative parameters, cytokine mRNA expressions, histopathology, and immunohistochemical studies were performed in liver and blood samples. The serum levels of alanine aminotransferase and aspartate aminotransferase and the mRNA expression of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta in the liver tissues were significantly increased in the group treated with P. The superoxide dismutase and glutathione parameters decreased and malondialdehyde levels increased in the livers of the rats treated with P. All these parameters were increased with both doses of the AML similar to the control group. A histopathological examination of the liver showed that AML administration ameliorated the P-induced inflammatory liver damage. In immunohistochemical staining, the expression of TNF-α in the cytoplasm of the hepatocytes was increased in the P group but not in other treatment groups when compared to the control. In conclusion, AML treatment showed significant protective effects against P-induced hepatotoxicity by increasing the activity of antioxidants and reducing inflammatory cytokines.