Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Methanol Extract of<i>Muntingia calabura</i>L. Leaves

Mahmood, Nur Diyana; Mamat, Siti Syariah; Kamisan, Farah Hidayah; Yahya, Farhana; Kamarolzaman, Mohamad Fauzi Fahmi; Nasir, Nurliana; Mohtarrudin, Norhafizah; Tohid, Siti Farah Md; Zakaria, Zaki Yamani

doi:10.1155/2014/695678

Cited by 54 publications

(59 citation statements)

References 40 publications

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“…These results indicate that captopril has hepatoprotective effects when evaluated through paracetamol induced toxicity model 14 . This result is in line with the study of Elena et al 12 and Nora…”

Section: Discussionmentioning

confidence: 62%

“…It is also known that many drugs and toxins can cause hepatotoxicity. Paracetamol is an over the counter drug that is reported to cause hepatotoxicity if taken in overdose 14 . Paracetamol is metabolized by cytochrome P-450 to N-acetyl-p-benzo-quinoneimine (NAPQI).…”

Section: Discussionmentioning

confidence: 99%

“…In one of the previous studies captopril is reported to enhance total glutathione content as well as glutathione peroxidase and glutathione reductase activities in various mouse tissues 12 . However, according to another study captopril decreased the activity of both glutathione peroxidase and glutathione reductase 13 Therefore, it was decided to evaluate the histopathological effects of captopril using paracetamol induced toxicity model 14 .…”

Section: Discussionmentioning

confidence: 99%

“…The administration of Paracetamol or normal saline was performed 24 hours after the last administration of captopril. After 48 hours of hepatic injury induction, the animals were then sacrificed and the liver was removed for histopathological studies 14,15 . …”

Section: High Dose Paracetamol (3000 Mg/kg)mentioning

confidence: 99%

“…The tissues were processed and embedded in paraffin wax and sectioned. Sections were stained with Haematoxylin and Eosin (H&E) dye for microscopic observation of histological changes in the liver 14,15 .…”

Section: Histological Studymentioning

confidence: 99%

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Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Al-Shaikh

Mudawi

Yassin

et al. 2016

AJPRHC

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Many patients may administered medications like captopril (ACE inhibitor) for treatment of chronic diseases and may also take Paracetamol as an Over The Counter (OTC) drug which may interact with captopril. Therefore, the aim of this study is to evaluate of the hepatoprotective effect of captopril on liver toxicity induced by low and high dose of paracetamol in rats. This study was conducted in two phases: first study for low dose of paracetamol (300 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were treated orally either 0.9 % Normal Saline (NS), captopril 20 mg/kg, paracetamol 300 mg/kg or captopril 20 mg/kg plus paracetamol 300 mg/kg for 10 consecutive days. Second study for single high dose of paracetamol (3000 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were pretreated orally either 0.9 % Normal Saline (NS) or captopril 20 mg/kg for 7 consecutive days followed by single oral administration of Paracetamol 3000 mg/kg or normal saline. The administration of Paracetamol or normal saline was performed 24 hours after the last administration of captopril. After 48 hours of hepatic injury induction, the animals were then sacrificed and the liver was removed for histopathological studies. Low dose (300 mg/kg) for 10 days and high single dose (3000 mg/kg) of paracetamol produced hepatotoxic effects. While captopril 20 mg/kg showed marked protection against changes induced by low and high dose of paracetamol on the liver.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: High Dose Paracetamol (3000 Mg/kg)mentioning

confidence: 99%

Section: Histological Studymentioning

confidence: 99%

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Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Al-Shaikh

Mudawi

Yassin

et al. 2016

AJPRHC

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Hepatoprotective effects of Juglans regia on carbon tetrachloride‐induced hepatotoxicity: In silico/in vivo approach

Pandey,

Thapa,

Kaundinnyayana

et al. 2024

Food Science & Nutrition

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Juglans regia L. is a well‐known therapeutic plant in Nepal, employed in traditional medicine for treating liver ailments. This study aimed to evaluate the in vivo and in silico liver‐protective effects of J. regia extract using a carbon tetrachloride (CCl4)‐induced hepatic damage rat model. Healthy male rats were randomly divided into six groups: normal control (distilled water 10 mL/kg), toxic control (distilled water 10 mL/kg), standard test (silymarin 100 mg/kg), and three groups receiving oral J. regia extracts (125, 250, and 500 mg/kg/day) for seven days. On the eighth day, carbon tetrachloride (CCl4) was administered intraperitoneally (i.p.) (1.5 mL/kg in 1:1 olive oil ratio for all groups, except the normal control). Rats were sacrificed on the ninth day, and blood was collected retro‐orbitally for liver blood injury tests and histopathological studies. Molecular docking was performed against cytochrome P450 2E1 (CYP450 2E1) enzyme for 16 selected phytoconstituents. J. regia, at doses of 125, 250, and 500 mg/kg, significantly reduced liver enzyme levels (alanine aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin), while increasing serum albumin. Histological analysis revealed mitigation of carbon tetrachloride (CCl4)‐induced liver injury, reducing fatty degeneration and necrosis. Molecular docking supported the findings, with Beta‐sitosterol and Betulinic acid exhibiting the best binding affinity of −9.2 and −9.1 kcal/mol, respectively. In conclusion, result suggests that J. regia showed dose‐dependent hepatoprotective activity in CCl4‐induced hepatotoxicity and it could be utilized as a promising hepatoprotective agent. This study suggests the hepatoprotective potential of J. regia bark extracts, emphasizing the need for further clinical validation.

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Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

Vangaveti

Das

Kumar

2020

J Biochem & Molecular Tox

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The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500 mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor‐alpha, prostaglandin E2), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)‐2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose‐dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX‐2 and iNOS immunoreactivity scores, further strengthened these findings. The hepatoprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long‐term CsA treatment to maintain their liver and kidney functions.

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Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Methanol Extract ofMuntingia calaburaL. Leaves

Cited by 54 publications

References 40 publications

Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Hepatoprotective effects of Juglans regia on carbon tetrachloride‐induced hepatotoxicity: In silico/in vivo approach

Metformin and silymarin afford protection in cyclosporine A induced hepatorenal toxicity in rat by modulating redox status and inflammation

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