A study of effect of Nigella sativa oil in paracetamol induced hepatotoxicity in albino rats

Background: Acetaminophen (paracetamol) toxicity is a common cause of drug‑induced hepatotoxicity in children and adults. Specific treatment of paracetamol induced hepatitis is available in the form of N‑acetylcysteine only. Nigella sativa (NS) is used for the treatment of various ailments. Many studies have shown that NS plant has hepatoprotective potential. Hence, this study study was carried out to explore the prophylactic and therapeutic effect of NSoil against hepatotoxicity induced by paracetamol.Methods: Hepatotoxicity was induced in rats by paracetamol and it was assessed using biochemical parameters such as serum (Sr.) alanine aminotransferase (ALT), Sr. aspartate aminotransferase (AST), Sr. bilurubin, Sr. alkaline phosphatase, and Sr. total protein. In addition, histopathological score was also assessed. The therapeutic and prophylactic effect of NSoil administration on paracetamol induced hepatotoxicity was investigated by using above mentioned biochemical and histopathological parameters.Results: Paracetamol administration leads to rise in serum liver enzymes ad fall in Sr. total protein levels. NS oil has heptoprotective effect. NS oil significantly reversed changes in serum levels of AST, ALT, alkaline phophatase, bilurubin, and total protein produced by paracetamol. Furthermore, histopathological changes produced by paracetamol were reversed.Conclusion: This study demonstrated that NS oil has hepatoprotective effect.NS oiladministration can prevent or reverse the hepatotoxicity induced by paracetamol

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

HEPATOPROTECTIVE EVALUATION OF EPALTES DIVARICATA (L.) CASS. WHOLE PLANT EXTRACTS AGAINST PARACETAMOL-INDUCED HEPATOTOXICITY IN RATS

Objective: The plant of Epaltes divaricata (L.) Cass. Traditionally used for jaundice. The present work aimed to investigate the hepatoprotective activity of alcohol and aqueous extract of the whole plant against paracetamol-induced hepatotoxicity in rats to substantiate its traditional use.Methods: The alcohol and aqueous (200 and 400 mg/kg) extract of Epaltes divaricata prepared by cold maceration were administered orally to the animals with hepatotoxicity induced by paracetamol (1000 mg/kg). Silymarine (40 mg/k) was given as reference standard. Hepatoprotective activity was assessed by estimating marker enzymes and by histopathological studies.Results: Both alcohol and aqueous (200 and 400 mg/kg) extract treatment significantly restored the paracetamol-induced elevations in levels of serum enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphate (ALP) and total bilirubin in a dose-dependent manner. Histopathological examination revealed that the treatment attenuated the paracetamol-induced damage to the liver. The hepatoprotective effect of both extracts was comparable to that of the standard hepatoprotective agent, silymarin.Conclusion: The alcohol and aqueous extract of E. divaricata exhibited hepatoprotective effect against paracetamol-induced liver damage in rats. This study also validated their traditional medicinal use in jaundice

Drug Hepatotoxicity: Environmental Factors

Drug-induced liver injury presents as various forms of acute and chronic liver disease. There is wide geographic variation in the most commonly implicated agents. Smoking can induce cytochrome P450 enzymes but this does not necessarily translate into clinically relevant drug-induced liver injury. Excessive alcohol consumption is a clear risk factor for intrinsic hepatotoxicity from acetaminophen and may predispose to injury from antituberculosis medications. Understanding of the role of infection, proinflammatory states, disorders of coagulation, and the hepatic clock in predisposing patients to drug-induced liver injury is evolving. More study focusing specifically on environmental risk factors predisposing patients to drug-induced liver injury is needed

Studies in acute liver failure

Acute liver failure (ALF) is a devastating condition with a high associated mortality rate. Paracetamol hepatotoxicity remains the leading cause of ALF in the developed world. The studies outlined in this thesis explore the current management of ALF, and systematically review the prognostic tests currently used in paracetamol-induced ALF. Using a database of over 900 acute liver injury patients, the impact of unintentional paracetamol overdose is retrospectively analysed, demonstrating a strong association between this mode of paracetamol overdose and adverse clinical outcomes, including the requirement for emergency orthotopic liver transplantation.Current prognostic tests for severe paracetamol-induced hepatotoxicity have been criticised for their relatively low sensitivity, with the result that not all patients who might benefit from tertiary level care are identified. This thesis demonstrates that the development of the Systemic Inflammatory Response Syndrome (SIRS) or extrahepatic organ failure is strongly associated with death following paracetamol overdose. Due to their very high sensitivity in this condition, both the SIRS and Sequential Organ Failure Assessment scores have potential as future gatekeepers to improve the triage of paracetamol overdose patients, thereby delivering tertiary level care to those most likely to require emergency transplantation.A greater understanding of the pathophysiological links between the initial hepatic injury and development of the SIRS could help to identify novel biomarkers for ALF, and help guide future therapeutic avenues. Using serum samples from a prospectively collected cohort of acute liver injury patients, this thesis identifies two novel biomarkers, serum ferritin and the long pentraxin PTX3, which show a strong association with outcome following paracetamol hepatotoxicity. These biomarkers illustrate the importance that the innate immune system plays in the pathogenesis of paracetamol-induced ALF, and identifies several exciting areas for future cellular and animal-based studies

Study of evaluation of hepatoprotective potential of lycopene in rat models of paracetamol and antitubercular drugs (isoniazid + rifampicin) induced hepatotoxicity

Background: The exact role of lycopene has not been studied in the past for its hepatoprotective effects. Hence it was decided to explore its anti-oxidant and anti-inflammatory properties in acute and chronic models of drug- induced hepatotoxicity with the aim to evaluate hepatoprotective potential in rat models of paracetamol and antitubercular drugs (isoniazid + rifampicin) induced hepatotoxicity.Methods: The study was carried out in 70 Wistar rats in two phases. In phase I, models of paracetamol and anti-tubercular drugs induced hepatotoxicity were standardized in 22 Wistar rats and in phase II, hepatoprotective potential of lycopene was evaluated in paracetamol and anti-tubercular drugs induced hepatic damage using 48 Wistar rats. The effects of lycopene were compared with silymarin.Results: There was a significant (p <0.05) reduction in serum bilirubin levels with silymarin and lycopene 10mg/kg treated groups signifying protection against hepatic damage, while vehicle control and lycopene 5mg/kg treated groups had high bilirubin values. Similarly, significant (p <0.001) reduction in the levels of serum transaminases were observed with all the treatment groups though more evident in the positive control and lycopene 10mg/kg treated groups.Conclusions: The results of the present study prove that lycopene exerts hepatoprotective effect against paracetamol and anti-tubercular drugs induced hepatic damage in rats. Lycopene needs to be evaluated in other models of hepatotoxicity and further studies are required to delineate its mechanism of action. Lycopene could be a potential hepatoprotective for clinical use in future

Hepatoprotective activity of fruit extract of Garcinia pedunculata

The objective of this study was to explore the hepatoprotective activity of fruits of Garcinia pedunculata in paracetamol-induced liver toxicity in rats. Paracetamol-induced hepatotoxicity was evaluated by an increase in serum transaminases and alkaline phosphatase activity. Histopathological observation showed extensive disturbance in the liver cytoarchitecture in comparison to normal control liver sections. Pre-treatment with aqueous extract of fruits of G. pedunculata prevented the paracetamol-induced increase in serum transaminases, alkaline phosphatase and histopathological changes. Based on the above observation it can be concluded that G. pedunculata pretreatment exhibited significant hepatoprotective activity against paracetamol-induced hepatotoxicity

HEPATOPROTECTIVE ACTIVITY OF SPHAERANTHUS AMARANTHOIDES WHOLE PLANT IN PARACETAMOL INDUCED HEPATOTOXICITY IN RATS

Objective: To evaluate the protective effect of ethanol extract of whole plant of Sphaeranthus amaranthoides against paracetamol induced hepatotoxicity in albino wistar rats.Methods: Liver damage was induced by administration of paracetamol orally at a dose of 2 g/kg body weight. Protective effect of the extract was determined by assessing the levels of serum enzymes like AST, ALT, ALP, total protein, total bilirubin, liver Malondialdehyde and glutathione levels. The extract was standardized by HPTLC method.Results: Administration of ethanol extract at 400 mg/kg b. wt showed significant (***P<0.001) reduction in elevated serum enzyme levels compared to paracetamol induced animals. Paracetamol induced liver toxicity decreased the liver glutathione level and increased the MDA level. The results of our study showed that ethanol extract at 400 mg/kg significantly increased glutathione content and decreased the MDA level indicating the protective role of Sphaeranthus amaranthoides ethanol extract against paracetamol induced liver toxicity.Conclusion: Sphaeranthus amaranthoides whole plant possesses potent hepatoprotective activity against paracetamol induced hepatotoxicity.Â