Evaluation of Hepatoprotective Effect of Vanillin in Isoniazid-Rifampicin Induced Hepatocellular Damage

The aim of this study was to evaluate the effect of Vernonia amygdalina leaf extract (VALE) on the carbon tetrachloride-induced hepatotoxicity (CCl4) in broiler chickens. A total of 360-day-old broilers were divided into 4 treatments of 90 birds each consisting of 6 replicates of 15 birds each. The treatments were birds offered 1 mL/kg BW saline (control group), 100 mg/kg BW VALE, 1 mL/kg BW CCl4 (CCl4-treated group), and 100 mg/kg BW VALE + 1 mL/kg BW CCl4 (VALE + CCl4 group). Blood samples were collected at 42 days of age and analyzed for the liver enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and selected biochemical parameters. The experiment was laid out in a completely randomized design. The results obtained showed that VALE had the potential to mitigate the adverse effects of CCl4 on protein and lipid metabolism as reflected in the low serum malondialdehyde (MDA) levels, which is a marker of lipid peroxidation. The aqueous extract of Vernonia amygdalina (VA) at a dose of 100 mg/kg body weight showed a moderate hepatoprotective effect by reducing serum AST levels (p < 0.05). The levels of serum AST, ALP, ALT, and GGT were significantly increased in CCl4-treated birds compared to the control group, reflecting carbon tetrachloride-induced liver damage. The VALE + CCl4 group showed a significantly higher amount of ALP compared to birds treated with carbon tetrachloride, suggesting a hepatoprotective effect. To conclude, Vernonia amygdalina aqueous extract can be used to confer protection against hepatotoxicity, which can induce severe hepatocellular damage in birds.

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An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage

10.1101/815241 ◽

2019 ◽

Author(s):

Zhang-He Goh ◽

Jie Kai Tee ◽

Han Kiat Ho

Keyword(s):

Herbal Product ◽

Complementary Therapy ◽

Hepatoprotective Effect ◽

Proof Of Concept ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Nutraceutical Compounds ◽

Hepatocellular Damage ◽

Drug Regimens

AbstractTuberculosis remains a significant infectious lung disease that affects millions of patients worldwide. Despite numerous existing drug regimens for tuberculosis, Drug-Induced Liver Injury is a major challenge that limits the effectiveness of these therapeutics. Two drugs that form the backbone of the commonly administered quadruple antitubercular regimen, i.e. pyrazinamide (PZA) and isoniazid (INH), are associated with such hepatotoxicity. The problem is compounded by the lack of safe and effective alternatives to the antitubercular regimen. Consequently, current research largely focuses on exploiting the hepatoprotective effect of nutraceutical compounds as complementary therapy. Silibinin, a herbal product widely believed to protect against various liver diseases, potentially provides a useful solution given its hepatoprotective mechanisms. In our study, we identified silibinin’s role in mitigating PZA- and INH-induced hepatotoxicity and elucidated a deeper mechanistic understanding of silibinin’s hepatoprotective ability. 25 μM silibinin preserved the viability of human foetal hepatocyte line LO2 when co-administered with 80 mM INH and decreased apoptosis induced by a combination of 40 mM INH and 10 mM PZA by reducing oxidative damage to mitochondria, proteins, and lipids. Taken together, this proof-of-concept forms the rational basis for the further investigation of silibinin’s hepatoprotective effect in subsequent preclinical studies and clinical trials.Graphical Abstract

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An Evaluation of the In Vitro Roles and Mechanisms of Silibinin in Reducing Pyrazinamide- and Isoniazid-Induced Hepatocellular Damage

International Journal of Molecular Sciences ◽

10.3390/ijms21103714 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3714

Author(s):

Zhang-He Goh ◽

Jie Kai Tee ◽

Han Kiat Ho

Keyword(s):

Herbal Product ◽

Complementary Therapy ◽

Hepatoprotective Effect ◽

Proof Of Concept ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Nutraceutical Compounds ◽

Hepatocellular Damage ◽

Drug Regimens

Tuberculosis remains a significant infectious lung disease that affects millions of patients worldwide. Despite numerous existing drug regimens for tuberculosis, drug-induced liver injury is a major challenge that limits the effectiveness of these therapeutics. Two drugs that form the backbone of the commonly administered quadruple antitubercular regimen, that is, pyrazinamide (PZA) and isoniazid (INH), are associated with such hepatotoxicity. Yet, we lack safe and effective alternatives to the antitubercular regimen. Consequently, current research largely focuses on exploiting the hepatoprotective effect of nutraceutical compounds as complementary therapy. Silibinin, a herbal product widely believed to protect against various liver diseases, potentially provides a useful solution given its hepatoprotective mechanisms. In our study, we identified silibinin’s role in mitigating PZA- and INH-induced hepatotoxicity and elucidated a deeper mechanistic understanding of silibinin’s hepatoprotective ability. Silibinin preserved the viability of human foetal hepatocyte line LO2 when co-administered with 80 mM INH and decreased apoptosis induced by a combination of 40 mM INH and 10 mM PZA by reducing oxidative damage to mitochondria, proteins, and lipids. Taken together, this proof-of-concept forms the rational basis for the further investigation of silibinin’s hepatoprotective effect in subsequent preclinical studies and clinical trials.

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Hepatoprotective Effect of Drynaria quercifolia Fronds Hydroalcoholic Extract and Isolated Constituent against CCl4-Induced Hepatocellular Damage

British Journal of Pharmaceutical Research ◽

10.9734/bjpr/2013/3620 ◽

2013 ◽

Vol 3 (4) ◽

pp. 563-578 ◽

Cited By ~ 1

Author(s):

Pradeep Kamboj

Keyword(s):

Hepatoprotective Effect ◽

Hydroalcoholic Extract ◽

Hepatocellular Damage

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Early Development of Drug-Induced Hepatic Necrosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066942 ◽

1971 ◽

Vol 29 ◽

pp. 576-577

Author(s):

F. G. Zaki ◽

E. Detzi ◽

C. H. Keysser

Keyword(s):

Early Development ◽

Hepatic Necrosis ◽

Screening Tests ◽

Dense Matrix ◽

Sprague Dawley ◽

Electron Microscopic ◽

Drug Induced ◽

Hepatocellular Damage ◽

Sprague Dawley Rats ◽

Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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