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Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats.
J Appl Toxicol. 2009 Mar; 29(2):156-64.JA

Abstract

Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Nogueira CW
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil. criswn@quimica.ufsm.br
Borges LP
No affiliation info available
Souza AC
No affiliation info available

MeSH

Administration, OralAlanine TransaminaseAnimalsAscorbic AcidAspartate AminotransferasesBenzene DerivativesBilirubinCarbon TetrachlorideCarbon Tetrachloride PoisoningCatalaseCreatinineDrug SynergismDrug-Related Side Effects and Adverse ReactionsLipid PeroxidationLiverMaleOrganoselenium CompoundsPorphobilinogen SynthaseRatsRats, WistarThiobarbituric Acid Reactive SubstancesUreagamma-Glutamyltransferase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18989868

Citation

Nogueira, Cristina W., et al. "Oral Administration of Diphenyl Diselenide Potentiates Hepatotoxicity Induced By Carbon Tetrachloride in Rats." Journal of Applied Toxicology : JAT, vol. 29, no. 2, 2009, pp. 156-64.
Nogueira CW, Borges LP, Souza AC. Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats. J Appl Toxicol. 2009;29(2):156-64.
Nogueira, C. W., Borges, L. P., & Souza, A. C. (2009). Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats. Journal of Applied Toxicology : JAT, 29(2), 156-64. https://doi.org/10.1002/jat.1394
Nogueira CW, Borges LP, Souza AC. Oral Administration of Diphenyl Diselenide Potentiates Hepatotoxicity Induced By Carbon Tetrachloride in Rats. J Appl Toxicol. 2009;29(2):156-64. PubMed PMID: 18989868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats. AU - Nogueira,Cristina W, AU - Borges,Lysandro Pinto, AU - Souza,Ana Cristina Guerra, PY - 2008/11/8/pubmed PY - 2009/7/29/medline PY - 2008/11/8/entrez SP - 156 EP - 64 JF - Journal of applied toxicology : JAT JO - J Appl Toxicol VL - 29 IS - 2 N2 - Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4. SN - 1099-1263 UR - https://www.unboundmedicine.com/medline/citation/18989868/Oral_administration_of_diphenyl_diselenide_potentiates_hepatotoxicity_induced_by_carbon_tetrachloride_in_rats_ L2 - https://doi.org/10.1002/jat.1394 DB - PRIME DP - Unbound Medicine ER -