Evaluation of the role of the antioxidant silymarin in modulating the in vivo genotoxicity of the antiviral drug ribavirin in mice

Noshy, Magda M.; Hussien, Nahed Ahmed; El-Ghor, Akmal A.

doi:10.1016/j.mrgentox.2012.12.012

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…This finding agrees with other investigations, which showed that silymarin is a potent antioxidant and might act as an antigenotoxic agent. 32,33 The renal system is one most damaged by Pb exposition. This study also showed that Pb induced renal toxicity, as evidenced by histopathological changes that were consistent with the observations of other investigators.…”

Section: Discussionmentioning

confidence: 99%

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Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats

et al. 2015

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We studied the effect of silymarin and dimercaptosuccinic acid (DMSA), a chelating agent that was administered individually or in combination against lead (Pb) toxicity in rats. Wistar rats (200 ± 20) were randomly divided into five groups. Group A served as a control. Groups B–E were exposed to 2000 ppm of lead acetate in drinking water for 8 weeks. Group B served as a positive control. Group C received silymarin (100 mg kg−1 orally) for 8 weeks. Group D received DMSA (75 mg kg−1 orally) once daily for the last 5 days of treatment. Group E received DMSA and silymarin as groups C and D, respectively. The effect of Pb was evaluated and accordingly the treatments on blood lead levels (BLLs), renal system, and genotoxic effects were calculated using comet assay. The BLLs were significantly increased following the exposition of lead acetate. The administration of silymarin and DMSA provided reduction in BLLs. Silymarin and DMSA provided significant protection on the genotoxic effect of Pb. The toxic effect of Pb on kidneys was also studied. Our data suggest that silymarin and DMSA improve the renal histopathological lesions.

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Section: Discussionmentioning

confidence: 99%

“…This finding agrees with other investigations, which showed that silymarin is a potent antioxidant and might act as an antigenotoxic agent. 32,33…”

Section: Discussionmentioning

confidence: 99%

Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats

et al. 2015

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“…Animals were administered selenomethionine (60 µg/kg, cumulative dose 600 µg/kg) (groups 3, 6, 9) or D-Pt (50 mg/kg, cumulative dose 500 mg/kg) (groups 4,7,10) per os every second day, starting from 2nd till 20th day of tumor inoculation. The chemotherapy scheme was developed based on NCI recommendations ( 20 ) and other studies describing combined use of anticancer drugs and antioxidants ( 21 , 22 ). Mice from the first (control) and second (NK/Ly lymphoma, untreated) groups received simultaneously the equivalent volume of 0.9% sodium chloride solution in a similar mode.…”

Section: Methodsmentioning

confidence: 99%

Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice

et al. 2016

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AimTo investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphoma-bearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone.MethodsThe hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, De Ritis ratio, and coenzyme A fractions by McDougal assay. Glutathione level in animal tissues was measured with Ellman reagent, and the activity of glutathione reductase, transferase, and peroxidase was measured using standard biochemical assays.ResultsD-pantethine (500 mg/kg) and, to a lower extent, selenomethionine (600 µg/kg) partially reduced the negative side effects (leukocytopenia and erythropenia) of Dx (5 mg/kg) in NK/Ly lymphoma bearing animals on the 14th day of their treatment. This increased animal survival time from 47-48 to 60+ days and improved the quality of their life. This ability of D-pantethine and selenomethionine was realized via hepatoprotective and immunomodulating activities. D-pantethine also restored the levels of acid-soluble and free CoA in the liver of tumor-bearing animals, while selenomethionine caused the recovery of glutathione peroxidase levels in the liver, which was significantly diminished under Dx treatment. Both compounds decreased glutathione level in the liver, which was considerably induced by Dx.ConclusionsAntioxidants selenomethionine and D-pantethine partially reversed the negative side effects of Dx in NK/Ly lymphoma-bearing mice and significantly increased the therapeutic efficiency of this drug in tumor treatment.

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“…Single strand conformational polymorphism polymerase chain reaction (SSCP-PCR) was carried out to screen mutations in the mitochondrial D-loop. First mitochondrial DNA was extracted from the liver and kidney tissues based on the protocol described by Noshy et al (2013), by gently homogenizing a small amount of tissue in cold homogenization buffer (100 mM Tris-HC1, pH 7.4, 250 mM sucrose, 10 mM EDTA), and centrifuged to remove nuclei and cellular debris. The supernatant was further centrifuged for 10 min at 4°C at 10,500 rpm (10,000 × g) then the mitochondrial pellet was resuspended in high-salt buffer (10 mM Tris-HCl pH 7.6, 10 mM KCl, 10 mM MgCl2, 0.4 M NaCl and 2 mM EDTA).…”

Section: Screening Mutations In Mitochondrial D-loop Using Sscp-pcrmentioning

confidence: 99%

Amelioration of cobalt oxide nanoparticles induced genomic and mitochondrial DNA damage and oxidative stress by omega-3 co-administration in mice

Mohamed

Hussien

2018

Caryologia

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Increased human exposure to cobalt oxide nanoparticles (CoO-NPs) because of their widespread use in many industrial and medical applications makes the study of genotoxicity and mutagenicity necessary. Therefore, this study was conducted to assess the genomic and mitochondrial DNA damage induction by CoO-NPs and the possible protective role of omega-3 in mice. The simultaneous administration of omega-3 significantly reduced DNA damage caused by CoO-NPs, which was evaluated by restoring the normal intact appearance of genomic DNA running on the agarose gel and normalizing fractionated DNA. The elevated malondialdehye (MDA) level and the reduced catalase (CAT) and glutathione peroxidase (Gpx) activities by CoO-NPs oral administration were normalized by omega-3 co-administration. Moreover, the omega-3 co-administration reduced the incidence of mutations induced by CoO-NPs in mitochondrial D-loop from 67% to 33%. We concluded that genomic and mitochondrial DNA damage and oxidative stress caused by CoO-NPs was mitigated by omega-3 co-administration.

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Evaluation of the role of the antioxidant silymarin in modulating the in vivo genotoxicity of the antiviral drug ribavirin in mice

Cited by 12 publications

References 42 publications

Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats

Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats

Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice

Amelioration of cobalt oxide nanoparticles induced genomic and mitochondrial DNA damage and oxidative stress by omega-3 co-administration in mice

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