Hepatoprotective Effect of Silymarin and Propolis in Chemically Induced Chronic Liver Injury in Rats

Hashem, Aml; Taha, Nabil M.; Mandour, Abdelwahab; Lebda, Mohamed A.; Balbaa, Mahmoud; Morshedy, Amany S. El

doi:10.5455/ajvs.212142

Cited by 6 publications

(8 citation statements)

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“…It was reported that in DEN induced hepatocarcinogens caused elevation in AFP level (which is widely used as tumor marker for diagnosis of HCC) associated with the increment in tumor growth and progression (Murugan et al,2015). Similarity, Hashem et al (2016) reported that a significant increase in AFP level was shown in DEN+CCl4 group. The increase in serum AFP concentration has been used as a clinical marker in the diagnosis and monitoring of HCC (Tork et al,2015).…”

Section: Resultssupporting

confidence: 79%

“…Similarity, Hemieda et al (2016) showed that treatment with DENA/CCl4 elevate the values of serum ALT, AST and ALP activities and total bilirubin level and markedly decreased serum total proteins and albumin concentrations. Also, Hashem et al (2016) confirmed that administration of DEN/CCl4 significantly increased liver weight, relative liver weight, AST, ALT and ALP while, body weight, total protein, albumin and A/G ratio were markedly decreased. Furthermore, Liver is the main site of DEN metabolism, the generation of ROS in the liver is recognized as an important contributor in DEN-induced damage (Faten et al,2014).…”

Section: Resultssupporting

confidence: 59%

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Moringa olifera Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Hussein

Abdel-Aal

Mady

2018

Benha Veterinary Medical Journal

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Moringa olifera was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of moringa olifera on Diethylnitrosamine (DEN) induced Hepatocellular carcinoma in rats. Fourty five male albino rats were divided into three groups. Group (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosoamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b.wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN then treated with moringa at a dose level of (500 mg/kg b.wt/orally) dissolved in distilled water for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis of liver tissue revealed significant upregulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with moringa olifera to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. These findings suggest the potential efficacy of moringa as an additional chemopreventive agent in treatment of hepatocellular carcionoma via initiation of tumor suppressor gene (P53) and modulating the metabolic activation of detoxification Enzyme (cytochrome P450 2E1) and antiinflammatory effect.

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Section: Resultssupporting

confidence: 79%

Section: Resultssupporting

confidence: 59%

Moringa olifera Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Hussein

Abdel-Aal

Mady

2018

Benha Veterinary Medical Journal

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“…It was reported that in DEN induced hepatocarcinogens caused elevation in AFP level (which is widely used as tumor marker for diagnosis of HCC) associated with the increment in tumor growth and progression (Murugan et al, 2015). Similarity, Hashem et al (2016) reported that a significant increase in AFP level was showen in DEN+CCl4 group. The increase in serum AFP concentration has been used as a clinical marker in the diagnosis and monitoring of HCC (Tork et al, 2015).…”

Section: Discussionsupporting

confidence: 76%

“…Similarly, Hemieda et al (2016) showed that treatment with DENA/CCl4 elevate the values of serum ALT, AST and ALP activities and total bilirubin level and markedly decreased serum total proteins and albumin concentrations. Also, Hashem et al (2016) confirmed that administration of DEN/CCl4 significantly increased liver weight, relative liver weight, AST, ALT and ALP while, body weight, total protein, albumin and A/G ratio were markedly decreased. Furthermore, Liver is the main site of DEN metabolism, the generation of ROS in the liver is recognized as an important contributor in DEN-induced damage (Faten et al, 2014).…”

Section: Discussionsupporting

confidence: 59%

Lycopene Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Hussein

EL-senosi

Hajjar

2018

Benha Veterinary Medical Journal

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Lycopene was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of Lycopene on diethylnitrosamine (DEN)-induced hepatocarcinogensis in rats. Forty-five male albino rats were divided into three groups. Group I (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b. wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN+CCl4 as in group II then treated with lycopene at a dose of (20 mg/kg b.wt/orally) dissolved in tween-80% for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with lycopene to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. Lycopene was able to mitigate liver tissue damage induced by DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level and ameliorate all serum liver function parameters. These findings suggested, the potential efficacy of lycopene as an additional chemo preventive agent in treatment of hepatocellular carcinoma by modulating the apoptosis, anti-inflammatory and detoxification effects.

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“…Also, it reduced iNOS, COX-2, and Bax and enhanced the expression of Bcl-2 and PCNA [139] . Further, the silymarin and propolis hepatoprotective effect in CCL4 hepatotoxicity in rats is mediated through antioxidant properties [140] . In vivo studies on rats, showed that LF causes portal fibrosis, sinusoidal congestion, and infiltration with periductal inflammatory cells.…”

Section: Studies Reporting the Drawbacks Of Leflunomide On The Livermentioning

confidence: 99%

Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review

Alamri

Elmeligy

Albalawi

et al. 2021

International Immunopharmacology

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Leflunomide (LF) represents the prototype member of dihydroorotate dehydrogenase (DHODH) enzyme inhibitors. DHODH is a mitochondrial inner membrane enzyme responsible for catalytic conversion of dihydroorotate into orotate, a rate-limiting step in the de novo synthesis of the pyrimidine nucleotides. LF produces cellular depletion of pyrimidine nucleotides required for cell growth and proliferation. Based on the affected cells the outcome can be attainable as immunosuppression, antiproliferative, and/or the recently gained attention of the antiviral potentials of LF and its new congeners. Also, protein tyrosine kinase inhibition is an additional mechanistic benefit of LF, which inhibits immunological events such as cellular expansion and immunoglobulin production with an enhanced release of immunosuppressant cytokines. LF is approved for the treatment of autoimmune arthritis of rheumatoid and psoriatic pathogenesis. Also, LF has been used off-label for the treatment of relapsing-remitting multiple sclerosis. However, LF antiviral activity is repurposed and under investigation with related compounds under a phase-I trial as a SARS CoV-2 antiviral in cases with COVID-19. Despite success in improving patients’ mobility and reducing joint destruction, reported events of LF-induced liver injury necessitated regulatory precautions. LF should not be used in patients with hepatic impairment or in combination with drugs elaborating a burden on the liver without regular monitoring of liver enzymes and serum bilirubin as safety biomarkers. This study aims to review the pharmacological and safety profile of LF with a focus on the LF-induced hepatic injury from the perspective of pathophysiology and possible protective agents.

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Hepatoprotective Effect of Silymarin and Propolis in Chemically Induced Chronic Liver Injury in Rats

Cited by 6 publications

References 0 publications

Moringa olifera Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Moringa olifera Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Lycopene Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review

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