Discovering the Hepatoprotective Properties of ARA290 in Acetaminophen-Induced Liver Toxicity

Acetaminophen has contributed to acute liver failure disease in more than half of the USA and Britain but as an analgesic and antipyretic it is very effective. For many decades in Europe, Middle East and Africa, Nigella sativa has been used for various medical purposes, it is part of the botanical family Ranunculaceae of Gently sloping plants, and is called black cumin seed., Nigella sativa conjugated sterols could be used as precursors to many hydrosoluble steroids for hemisynthesis. The aim of the Study is to examine the promising hepatoprotective effects of Nigella sativa against Acetaminopheninduce hepatotoxicity in mice in this experiment Forty adult male albino mice, incorporated in the experiment and Acetaminophenwas used to induce hepatotoxicity in a dose of 1 gm /kg by the oral route. A number of biochemical and histopathological tests have been used to evaluate liver damage and Nigella sativa protective effects. The result showed a significant protective effect of Nigella sativa against acetaminophenhepatotoxic effect as Nigella sativa in this study tended to normalize the serum levels of liver enzymes, and the protective effects observed clearly by the histopathological evaluation confirming that it effectively protected mouse livers against severe damage caused by acetaminophen. Conclusion in our study it shows that Nigella sativa have a very significant protective effects against acetaminophen induced liver toxicity which is recommended to be fully investigation on human especially to people on risk of acetaminophen liver toxicity

Acetaminophen has contributed to acute liver failure disease in more than half of the USA and Britain but as an analgesic and antipyretic it is very effective. For many decades in Europe, Middle East and Africa, Nigella sativa has been used for various medical purposes, it is part of the botanical family Ranunculaceae of
 
 Gently sloping plants, and is called black cumin seed., Nigella sativa conjugated sterols could be used as precursors to many hydrosoluble steroids for hemisynthesis. The aim of the Study is to examine the promising hepatoprotective effects of Nigella sativa against Acetaminopheninduce hepatotoxicity in mice in this experiment Forty adult male albino mice, incorporated in the experiment and Acetaminophenwas used to induce hepatotoxicity in a dose of 1 gm /kg by the oral route.
 A number of biochemical and histopathological tests have been used to evaluate liver damage and Nigella sativa protective effects. The result showed a significant protective effect of Nigella sativa against acetaminophenhepatotoxic effect as Nigella sativa in this study tended to normalize the serum levels of liver enzymes, and the protective effects observed clearly by the histopathological evaluation confirming that it effectively protected mouse livers against severe damage caused by acetaminophen. Conclusion in our study it shows that Nigella sativa have a very significant protective effects against acetaminophen induced liver toxicity which is recommended to be fully investigation on human especially to people on risk of acetaminophen liver toxicity

Background: Liver injury is a common reason for drugs to be withdrawn from the market. Treatment options for common liver disease are limited, and therapy with modern medicines may lack effectiveness. Caulerpa lentillifera may have strong antioxidant systems that protect the plant from oxidative damage caused by the environment.Objectives: The main objective of this study was to evaluate the hepatoprotective effect of the methanolic extract of C. lentillifera against acetaminophen-induced liver toxicity in juvenile zebrafish (Danio rerio). Methods: Juvenile zebrafish (aged 1–3 months) were exposed to 10 mikromolar and 25 mikromolar acetaminophen (N-acetyl-p-aminophenol; APAP) to induce liver damage. C. lentillifera methanolic extracts (0.01 mg/L, 0.02 mg/L and 0.03 mg/L), were concomitantly added to individual tanks containing 0.01 M or 0.025 M APAP. The positive control group was treated with N-acetylcysteine/NAC (0.01 M) and silymarin (0.01 mg/L, 0.02 mg/L and 0.03 mg/L). Hematoxylin and Eosin (H&E) staining revealed the extent of liver injury through the presence of hepatic necrosis, vacuolization, leukocyte infiltration, and ballooning. The antioxidant mechanism of hepatoprotective activity was assessed by a DPPH free radical scavenging assay.Result: C. lentillifera extracts reduced the mortality of juvenile zebrafish when simultaneously exposed to APAP. Upon histopathological examination of the liver tissue of juvenile zebrafish, the group treated with the 0.01 M APAP together with the highest concentration of C. lentillifera extract showed minimal liver injury compared to the groups exposed 0.025 M APAP. However, the DPPH free radical scavenging assay performed using 24–36 mg/mL C. lentillifera extracts showed a minimal effect on the free radical scavenging activity.Conclusion: The histopathological analysis of the liver showed that C. lentillifera extract prevented the progression of liver damage caused by APAP. The results of DPPH free radical scavenging assay indicated that the hepatoprotective activity of C. lentillifera extract might have other antioxidant mechanisms aside from free radical scavenging. In order to effectively assess the improvement in the survival rate of juvenile zebrafish, longer exposure in the treatments is recommendedKeywords: C. lentillifera; juvenile zebrafish; hepatoprotective; drug-induced liver injury (DILI)

Acetaminophen-induced liver toxicity is the most frequent precipitating cause of acute liver failure and liver transplant, but contemporary medical practice has mainly focused on patient management after a liver injury has been induced. An integrative genetic, transcriptional, and two-dimensional NMR-based metabolomic analysis performed using multiple inbred mouse strains, along with knowledge-based filtering of these data, identified betaine-homocysteine methyltransferase 2 (Bhmt2) as a diet-dependent genetic factor that affected susceptibility to acetaminophen-induced liver toxicity in mice. Through an effect on methionine and glutathione biosynthesis, Bhmt2 could utilize its substrate (S-methylmethionine [SMM]) to confer protection against acetaminophen-induced injury in vivo. Since SMM is only synthesized in plants, Bhmt2 exerts its beneficial effect in a diet-dependent manner. Identification of Bhmt2 and the affected biosynthetic pathway demonstrates how a novel method of integrative genomic analysis in mice can provide a unique and clinically applicable approach to a major public health problem.

Background: Medicinal plants are widely used in Nigeria because they are believed to be effective in the treatment of various medical conditions and are also easily accessable with minimal side effect.
 Aim: This study evaluates the prophylactic and therapeutic effects of different doses (200 mg/kg, 400 mg/kg and 800 mg/kg body weight) of Costus afer on lipid profile of 50 male albino rats.
 Methodology: The research study was divided into 2 phases with 25 rats used for each phases. The 25 rats used for each phase were randomly selected into 5 groups with each group containing 5 rats. The rats used for the prophylactic phase were induced with 800 mg/kg body weight paracetamol for liver toxicity after administration of the various concentrations of aqueous stem extract of C. afer for 28 days while those used during the therapeutic phase were administered with the various concentrations of aqueous stem extract of C. afer following confirmation of liver toxicity using 800 mg/kg body weight acetaminophen. The effect of the aqueous extract was assessed by measuring the serum concentration of total cholesterol, triglycerides and high density lipoprotein using Randox reagent, while low density lipoprotein was calculated from the other parameters. Atherogenic ratios were also computed. The result obtained from the experiment was subjected to statistical analysis using Graph pad prism version 5.3 and values were considered significant at p<0.05.
 Results: Total cholesterol, triglycerides and LDL levels were significantly (p<0.05) reduced and HDL significantly increased in the treatment groups (prophylactic and therapeutic phases) compared to the positive control. When both phases were compared, total cholesterol and triglycerides showed significant (p<0.05) difference in concentration in groups fed with 400 mg/kg, 200 mgkg while LDL-C showed significant (p<0.05) variation between the two phases only at 400 mg/kg body weight. The extracts were also found to significantly (p<0.05) reduce the atherogenic status of the albino rats in both phases of treatment and between each treatment phase.
 Conclusion: Findings from this study suggest that Costus afer possesses the ability to regulate paracetamol induced dyslipidaemia and improve the anti-atherogenic status of treated albino rats.

Aim To study the comparative effect of acetaminophen with aqueous Neem leaf extract (Azadirachta Indica) and vitamin E mediated liver toxicity on the basis of liver enzymes. Methods: A total of sixty (60) Wistar rats of either sex were divided equally into four groups. Each groupwas made up of 15 animals. Group A was the control group. Animals in Group B were treated with a single oral dose of 2 mg / kg b / w Paracetamol. Group C animals with 500 mg / kg b / w oral Neem extract for 15 days with oral administration of 2 mg / kg b / w oral Paracetamol. In Group D, animals received the same dose of Paracetamol and 100 mg / kg b / w intra-peritoneal vitamin E for 15 days, respectively. The liver enzymes ALT,AST, and ALP were then evaluated. Data was analyzed using SPSS Version 20.0 with level of significance being kept at p-value ≤0.05 Results: In the 4 groups, The ALT values were 22.8 (Group A), 100 (Group B), 29.11 (Group C), and 31.16 U/L (Group D). The AST values were 25 (Group A), 40 (Group B), 20 (Group C), and 15 (Group D) U/L. The ALP values were 220 (Group A), 445 (Group B), 242 (Group C), and 244 (Group D) U/L. There was significant increase in liver enzymes were found in Group B after induction of Paracetamol toxicity, however, hepatoprotective effects could be seen in the intervention Group C and D Conclusion: Azadirachta Indica and Vitamin E showed hepatoprotective effects on the Wistar rats that were subjected to Paracetamol Key words: Azadirachta Indicaleaf extract, Vitamin E, Paracetamol, Wistar rats

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

BackgroundPolysaccharides from seaweeds have been reported to possess biological activities with potential medicinal value. Present study was aimed to investigate hepatoprotective effect of crude sulphated polysaccharides extracted from Sargassum swartzii against acetaminophen-induced liver injury.MethodsThe polysaccharides from S. swartzii was extracted at room temperature and at 70 °C and named as EW1 and EW2. These fraction was given orally to rats at 200 mg/kg body weight. Liver injury was induced by single intraperitoneal injection of acetaminophen. Hepatic marker enzymes; alanine aminotransferases (ALT), aspartate aminotransferases (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and other biochemical parameters; glucose, triglycerides, cholesterol, urea and creatinine were estimated in serum, while hepatic glutathione (GSH) and lipid peroxidation were measured in liver tissue. Histopathology of liver tissues was also carried out.ResultsTreatment with polysaccharides EW1 & EW2 fractions significantly (p < 0.05) reduced the hepatic marker enzymes and other biochemical parameters along with increased GSH and reduced lipid peroxidation. The EW1 fraction of crude sulphated polysaccharides produced hepatoprotection more or less equivalent to silymarin (35 mg/kg), a commercial herbal drug, while some parameters showed better results than silymarin. These results were further confirmed with histology of liver.ConclusionThis study suggests that crude polysaccharides of S. swartzii has ability to protect against liver toxicity similar and/or better than silymarin (a standard drug) based on biochemical and histological findings. However toxicological studies would be recommended to evaluate any toxic effect of Sargassum swartzii.

The defense role of luteolin-β-CD-MOF against acetaminophen induced liver toxicity by regulating of bile acids metabolism and gut microbiota.

Antioxidant and hepatoprotective actions of the mold Monascus anka (also called Beni-Koji in Japan) against acetaminophen (AAP)-induced liver toxicity were investigated. Serum aspartate aminotransferase and glutathione 5-transferase (GST) activities increased by AAP (180 mg/kg, i.p.) treatment were depressed when the Beni-Koji preparation (4 ml/kg, i.p.) was given 15 and 1 hr before AAP administration. The decrease in liver cytosolic GST activity by AAP, reflecting the release of the enzyme into serum, was also blocked by the mold. Cytochrome P450 activity was inhibited by the Beni-Koji preparation. These results suggest that M. anka prevents AAP-induced liver toxicity by both antioxidant action and the inhibition of AAP metabolism.

Effectiveness of metyrapone in the treatment of acetaminophen toxicity in mice

Sa1805 - Novel Immunomodulatory Role of Aspartate and Nmda Receptor in Acetaminophen Induced Liver Toxicity and Acute Pancreatitis

Owning to changes in living pattern of humans and constant environmental changes, different life challenging diseases now exist. Traditional system has clam that some of these diseases could be cured with plant. Plants and their components are source of large amount of drugs. This study was design to examine the protective effect of Myrianthus arboreus leaves extract against acetaminophen induced liver toxicity in rats. A suspension of 750 mg/kg acetaminophen was administered once every 72 hours to induce toxicity in the rats. Oral administration of 500, 1000 and 2000 mg/kg body weight of the extract and 100 mg/kg of silymarine (reference drug) were administered for 10 days. The result of effect of pretreatment with Myrianthus aboreus leaves on the enzyme makers of tissue damage in acetaminophen induced toxicity showed significant different when compared with the result of group induced without pretreatment. The values of AST, ALT and ALP in the untreated group significantly (p&lt;0.05) increased. Elevated serum level in these enzymes revealed the integrity and functionality of the liver. Thus the increased value of these enzymes indicates damage to the liver by the induced acetaminophen. Also the values of non-enzyme markers (T.B., ALB and TG) for the treated groups decreased when compared with the untreated group. The significant different in the values between the groups pretreated with Myrianthus aboreus leaves and the untreated group showed that MA extract could protect the liver.

English

Hepatoprotective Effect of Silybon 140® on Acetaminophen induced Liver Toxicity in Nigerian Local Dogs