Reduction of acute hepatic damage induced by acetaminophen after treatment with diphenyl diselenide in mice.
In this study, the authors evaluated the ability of diphenyl diselenide (PhSe)(2) to reverse acute hepatic failure induced by acetaminophen (APAP) in mice. The animals received an APAP dose of 600 mg/kg intraperitoneally (i.p.), and then 1 hour later, they received 15.6 mg/kg i.p. of (PhSe)(2). Three hours after (PhSe)(2) administration, the animals were sacrificed and blood and liver samples were collected for analysis. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), 2',7'-dichlorofluorescein (DFC), catalase activity (CAT), and myeloperoxidase (MPO) activity were determined in the liver. A methyl-tetrazolium reduction (MTT) assay was also performed on the liver. Histopathological studies were conducted in all groups. Exposure of animals to APAP induced oxidative stress, increased lipid peroxidation (LPO), and the generation of reactive species, reduced the levels of GSH, and caused an increase in the MPO activity. Treatment with (PhSe)(2) reduced LPO and the formation of reactive species and inhibited the processes of inflammation, reducing the hepatic damage induced by APAP. The results of this study show that (PhSe)(2) is a promising therapeutic option for the treatment of acute hepatic failure.
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS, Brasil.
Edovando J F
EJ
da Rosa
Michele Hinerasky
MH
da Silva
Nelson Rodrigues
NR
Carvalho
Jessika Cristina
JC
Bridi
João Batista
JB
da Rocha
Sara
S
Carbajo-Pescador
Jose Luiz
JL
Mauriz
Javier
J
González-Gallego
Félix Alexandre Antunes
FA
Soares
D000082:Acetaminophen / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D020011:Protective Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D000082:Acetaminophen; D002374:Catalase; D009195:Peroxidase; D005978:Glutathione; D019803:Glutathione Disulfide