scholarly journals HEPATOPROTECTIVE EFFECT OF MELATONIN ON PARACETAMOL INDUCED HEPATOTOXICITY IN ALBINO RATS

2021 ◽  
pp. 102-105
Author(s):  
DEEPAK SHANKARAPPA ◽  
LOURDU JAFRIN A ◽  
JAYAPRIYA B ◽  
MAHARANI B
Keyword(s):  
Liver Injury ◽  
Liver Function Tests ◽  
Vital Role ◽  
Hepatoprotective Effect ◽  
Albino Rats ◽  
Toxic Metabolite ◽  
Drug Induced ◽  
Alternative Drug ◽  
Acetyl Cysteine ◽  
Dunnett's Test

Objective: Liver is the most important organ involved in the biotransformation of drugs and hence also a prime site for drug-induced liver injury (DILI). Among the hepatotoxic drugs, paracetamol which is commonly used is a major offender, leading to about 40% of DILI. N-acetyl cysteine is commonly used to manage paracetamol poisoning. However, it has its own disadvantages. This study has been designed to probe into the possibility of an alternative drug for paracetamol-induced hepatotoxicity. The objective is to study the hepatoprotective effect of melatonin on paracetamol-induced hepatotoxicity in albino rats. Materials and Methods: After prior approval from the IAEC, 36 albino rats were divided into six groups of six each. Each group received distilled water, paracetamol, paracetamol+N-acetyl cysteine, paracetamol+melatonin, and paracetamol+melatonin+N-acetyl cysteine, respectively. The liver function tests and histopathology of the liver of all the groups were compared. One-way ANOVA and post hoc Dunnett’s test were used. Results: Melatonin alone and in combination with N-acetyl cysteine is found to have significant hepatoprotective effect in paracetamol-induced acute liver injury. Conclusion: The main reason for hepatotoxicity is depletion of glutathione which is essential for conjugating the toxic metabolite N acetyl-p- benzoquinonimine (NAPQI) and CYP2E1 is playing the vital role of being the rate limiting enzyme initiating the cascade of events leading to acetaminophen hepatotoxicity. This is postulated to be reversed by melatonin.

scholarly journals Hepatoprotective effect of DL-methionine on diclofenac-induced hepatotoxicity in albino rats: an experimental study

2018 ◽  
Vol 6 (3) ◽  
pp. 802 ◽  
Author(s):  
Ervilla Dass ◽  
Bhagya Manoj Sattigeri
Keyword(s):  
Liver Injury ◽  
Diclofenac Sodium ◽  
Normal Liver ◽  
Concomitant Administration ◽  
Positive Control ◽  
Hepatoprotective Effect ◽  
Albino Rats ◽  
Histopathological Study ◽  
Drug Induced ◽  
Control Drug

Background: Liver is the main detoxifying organ, which is affected by most of the drugs and xenobiotic agents that could result in liver damage. The present study was designed to evaluate the hepatoprotective effect of DL-Methionine against experimentally induced liver injury in albino rats.Methods: Hepatotoxicity was induced by administering high doses of positive control drug Diclofenac sodium in albino rats, which was confirmed by estimating Liver Function Tests. Hepatoprotective effect was determined by administering DL- Methionine concomitantly with positive control drug. Albino rats were administered with DL-Methionine (700 mg/kg and 1400 mg/kg) respectively as a single oral dose, concomitantly with positive control drug Diclofenac sodium (96 mg/kg and 240 mg/kg) respectively. After 24-hours of post-treatment, serum levels of the liver enzymes were evaluated to demonstrate the hepatoprotective effect of DL-Methionine on drug-induced hepatotoxicity, and all the liver samples were examined for the histopathological study.Results: Significant increase in serum transaminase enzymes were observed by the positive control drug Diclofenac sodium. There was significant reduction in the serum transaminases on concomitant administration of DL-Methionine with Diclofenac sodium. Liver injury induced by positive control drug; and its protection with DL-Methionine was revealed by histopathological study. The combination of Diclofenac sodium and DL-Methionine showed no significant histopathological difference when compared to the normal liver section.Conclusions: The results reveal that, DL-Methionine significantly prevented the rise in transaminases levels produced by hepatotoxic doses of the positive control drug.

scholarly journals STANDARDIZATION OF MODEL OF INDUCTION OF HEPATOTOXICITY WITH ANTI-TUBERCULOSIS DRUGS IN WISTAR ALBINO RATS

2017 ◽  
Vol 10 (6) ◽  
pp. 150
Author(s):  
Sarita M Kapgate ◽  
Abhijit B Patil
Keyword(s):  
Liver Injury ◽  
Animal Studies ◽  
Hepatic Injury ◽  
Albino Rats ◽  
Histopathological Changes ◽  
First Line ◽  
Drug Induced ◽  
Significant Development ◽  
Reported Study ◽  
Wistar Albino Rats

Objective: The objective of the study to standardize the model of hepatotoxicity induced by ATT drugs in Wistar Albino rats. Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), the first line drugs used in the treatment of tuberculosis (TB) associated with the potential adverse effect. Numerous animal studies were reported endeavoring induction and cure of anti-TB (ATT) drug-induced hepatotoxicity using herbal and chemical drugs. However, the previous reported study failed to replicate where Wistar albino rats were treated with INH, RMP, and PZA and had shown the significant development of liver injury. Hence in present paper, aimed to develop a standardize model of induction of hepatotoxicity with ATT drugs.Methods: Wistar rats were treated with ATT drugs in combination in various doses up to 4-8 weeks. Total nine experiments were conducted to achieve successful hepatotoxicity. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were the biochemical parameters of assessment. Histopathological changes in the liver were also examined.Results: No evidence of any liver injury or an inflammatory infiltrate has been observed as had been reported in the previous studies. Rather decrease in serum ALT levels has been observed by researcher. In short, hepatic injury cannot be developed with the doses used in previous reported papers. The successful attempt to induce hepatotoxicity can be achieved with the doses of INH - 100, RMP - 300, PZA - 700 mg/kg. The findings were confirmed by the raised ALT, AST, and ALP levels compared with baseline. The histopathological changes also support the findings.Conclusion: The dose of INH - 100, RMP – 300 and PZM - 700 mg/kg. Succeeds to induce hepatotoxicity in Wistar albino rats and Swiss albino mice as well.

Thyrotoxic hepatitis

2017 ◽  
Vol 63 (1) ◽  
pp. 46-50
Author(s):  
Dmitrij V. Pikulev ◽  
Aleksej V. Klemenov
Keyword(s):  
Liver Injury ◽  
Clinical Symptoms ◽  
Correct Diagnosis ◽  
Clinical Signs ◽  
Rare Condition ◽  
Liver Function Tests ◽  
Biliary Cirrhosis ◽  
Liver Pathology ◽  
Drug Induced ◽  
Clinical Variants

In most cases, liver pathology in hyperthyroidism is confined to asymptomatic changes in laboratory indices, while clinical signs are much rarer. Three clinical variants of liver pathology in patients with hyperthyroidism can be differentiated: drug-induced hepatitis that develop in response to administration of thyrostatic agents (mainly propylthiouracil); concomitant autoimmune liver diseases (autoimmune hepatitis, primary biliary cirrhosis), and hepatopathies as a direct manifestation of thyrotoxicosis (thyrotoxic hepatitis). Thyrotoxic hepatitis is a rare condition difficult to diagnose. The variety of etiological factor of liver pathology in hyperthyroidism, universal clinical symptoms, and the lack of specific histological markers make it difficult to make a correct diagnosis. A clinical case of Graves’ disease complicated with severe thyrotoxic hepatitis, the edema-ascites syndrome and hyperbilirubinemia is reported. The patient was diagnosed with thyrotoxic hepatitis after all other reasons for liver pathology have been ruled out. The concomitant thyrogenic myocardiodystrophy, cardiomegaly and atrial fibrillation required ruling out the diagnosis of cardiogenic liver injury and made diagnosing more difficult. Normalization of the thyroid status in patients receiving mercazolyl therapy was accompanied by alleviation of clinical symptoms of hepatitis and the positive dynamics of the indices of liver function tests. A brief review of the data on clinical variants and mechanisms of liver injury in patients with thyrotoxicosis is presented.

scholarly journals A Patient with Nafcillin-Associated Drug-Induced Liver Failure

2017 ◽  
Vol 11 (3) ◽  
pp. 564-568 ◽  
Author(s):  
Qin Rao ◽  
Isaiah Schuster ◽  
Talal Seoud ◽  
Kevin Zarrabi ◽  
Nirvani Goolsarran
Keyword(s):  
Liver Injury ◽  
Liver Function ◽  
Liver Failure ◽  
Acute Liver Injury ◽  
Early Recognition ◽  
Antibiotic Use ◽  
Liver Function Tests ◽  
The United States ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient’s lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient’s liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

scholarly journals Hepatoprotective effect of aqueous extract of Melothria perpusilla against carbon tetrachloride induced liver injury in albino rats

2017 ◽  
Vol 5 (3) ◽  
pp. 806 ◽  
Author(s):  
Nokul S. Yengkhom ◽  
Ngangom Gunindro ◽  
Sania M. Kholi ◽  
Rakesh S. Moirangthem ◽  
Bharati D. Rajkumari
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Aqueous Extract ◽  
Liquid Paraffin ◽  
Herbal Medicines ◽  
Modern Medicine ◽  
Hepatoprotective Effect ◽  
Albino Rats ◽  
Group Iii ◽  
Group I

Background: In absence of reliable hepatoprotective drug in modern medicine, the traditional herbal medicines have been emphasized. Present study was designed to assess hepatoprotective effect of aqueous extract of Melothria perpusilla (AEMP) against carbon tetrachloride (CCl4) induced liver injury.Methods: Five groups of animals with 6 rats in each were treated for 7 days.  Group I received 1% gum acacia in distilled water (1 ml/200 g p.o.) daily.  Group II, III, IV and V received CCl4 in liquid paraffin (1 ml/kg s.c.) on day 2, 4 and 6. Group III, IV and V were treated respectively with silymarin (100 mg/kg p.o.), AEMP- 200 and 400 mg/kg p.o. daily. On day 8, liver injury was assessed by measuring serum ALT, AST, ALP and bilirubin.Results: ALT, AST, ALP and bilirubin were significantly reduced in groups receiving both CCl4 and AEMP when compared with CCl4 treated group.Conclusions: AEMP produced hepatoprotective effect against CCl4 induced liver injury.

Quercetin Modulates Nrf2 and NF-κB/TLR-4 Pathways to Protect against Isoniazid and Rifampicin Induced Hepatotoxicity in vivo

2021 ◽  
Author(s):  
Sukumaran Sanjay ◽  
Chandrashekaran Girish ◽  
Pampa Ch Toi ◽  
Zachariah Bobby
Keyword(s):  
Liver Injury ◽  
Liver Function Tests ◽  
Treated Group ◽  
Hepatic Necrosis ◽  
Drug Induced ◽  
Rifampicin Treatment ◽  
Nrf2 Activation ◽  
Ifn Γ ◽  
Endogenous Antioxidant

Isoniazid and rifampicin are crucial for treating tuberculosis (TB); however, they can cause severe hepatotoxicity leading to liver failure. Therapeutic options are limited and ineffective. We hypothesized that prophylaxis with quercetin attenuates isoniazid and rifampicin induced liver injury. We randomly divided Wistar rats into seven groups (n=6). The animals received isoniazid and rifampicin or were co-treated with quercetin or silymarin for 28 days. The protective effect of quercetin was assessed using liver function tests and liver histology. NRF2 and NF-κB pathways were explored to elucidate the mechanism of action. Quercetin co-administration prevented the elevation of ALT, AST, ALP and bilirubin compared to isoniazid and rifampicin treatment alone. In the histological analysis, we observed that quercetin prophylaxis lessened the severity of hepatic necrosis and inflammation compared to the anti-TB drug treated group. Quercetin attenuated anti-TB drug induced oxidative stress by increasing NRF2 activation and expression, boosting endogenous antioxidant levels. Additionally, quercetin blocked inflammatory mediators HMGB-1 and IFN-γ, inhibiting activation of the NF-κB/TLR-4 axis. Quercetin protects against anti-TB liver injury by activating NRF2 and blocking NF-κB/TLR-4.

Prednisolone: role in amoxicillin–clavulanate-induced cholestatic liver injury

2021 ◽  
Vol 14 (4) ◽  
pp. e239488
Author(s):  
Melvin Qiyu Lee ◽  
Royale Chigozie ◽  
Irfan Khan ◽  
Gerard O'Mara
Keyword(s):  
Liver Injury ◽  
Liver Function Tests ◽  
Hepatocellular Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
The Us ◽  
Common Causes ◽  
Amoxicillin Clavulanate ◽  
The Common ◽  
Cholestatic Liver Injury

A 68-year-old patient presented with symptoms of a urinary tract infection. A deterioration in the patient’s liver function tests (LFTs) was noted 1 week following completion of a course of amoxicillin–clavunalate. This progressively worsened, reaching its peak by day 30. Our investigations excluded other possible causes for deranged LFTs and there was no improvement of same despite reduced dosing of potentially hepatotoxic medications.A trial of 30 mg/day prednisolone was commenced, resulting in an immediate and progressive improvement in LFTs to baseline over a period of 22 days and an improvement in constitutional symptoms such as tiredness and poor appetite. Drug-induced liver injury (DILI) is one of the common causes of acute hepatitis and a leading cause of acute liver failure in the US and Europe. Patterns of DILI can be generally divided into: (1) hepatocellular injury, (2) cholestatic injury and (3) mixed injury.

scholarly journals Optimizing diagnostic approach to drug-induced liver injury

2018 ◽  
Vol 12 (3) ◽  
pp. 180-189 ◽  
Author(s):  
Maria Giovanna Minissale ◽  
Maurizio Soresi ◽  
Massimo Galia ◽  
Francesco Agnello ◽  
Lydia Giannitrapani ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Abdominal Ultrasound ◽  
Liver Function Tests ◽  
Accurate Method ◽  
Focal Lesions ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Drug-induced liver injury (DILI) is often a trial even to expert clinicians, because sometimes diagnosis is not easy to be made. Guidelines of the American College of Gastroenterology (ACG) yielded in 2014, help to better understand the problem. The diagnosis of DILI is made through a detailed evaluation of clinical, serological, radiological and histological aspects. Biochemical data include liver function tests that allow to assess the pattern of damage, such as hepatocellular, cholestatic and mixed liver injury; serological data include testing for major and possibly minor hepatotropic viruses, non-organ specific autoantibodies. Clinical scenario might include jaundice, nausea, vomiting and extra-hepatic manifestations such as fever, pruritus, rash and eosinophilia. Investigation of the potential culprit drugs should involve firstly the temporal relationship between intake of the medication and onset of symptoms, thus the improvement after drug withdrawal. Overall, to complete the diagnostic evaluation, an abdominal ultrasound can be performed, as well as measurement of liver stiffness by transient elastography, and finally liver biopsy, which still represents the most accurate method to definitely assess liver damage. Sometimes, in such cases, computed tomography scan and magnetic resonance could help in the diagnosis of cases presenting with focal lesions of the liver, with cholestatic-like disease or vascular alterations, such as veno-occlusive disease. DILI diagnostic criteria help clinicians thinking of liver injury induced by drug, excluding other causes of liver disease. According to severity of liver damage and type of drug, it is possible to carefully predict the patient’s outcome.

Sign in / Sign up

Export Citation Format

Share Document