Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942004000500004
Brazilian Journal of Anesthesiology
Scientific Article

Determinação das substâncias reativas ao ácido tiobarbitúrico como indicador da peroxidação lipídica em ratos tratados com sevoflurano

Thiobarbituric acid reactive substances as an index of lipid peroxidation in sevoflurane-treated rats

Francisco José Lucena Bezerra; Adriana Augusto Rezende; Sara Jane Rodrigues; Maria das Graças Almeida

http://dx.doi.org/10.1590/S0034-70942004000500004 Braz J Anesthesiol, vol.54, n5, p.640-649, 2004
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Resumo

JUSTIFICATIVA E OBJETIVOS: O sevoflurano é um éter fluorado de baixa solubilidade sangüínea e sua biotransformação ocorre por meio do sistema enzimático hepático oxidativo que envolve o citocromo P450 2E1. A peroxidação lipídica ocorre durante o processo de biotransformação dos éteres sob ação do citocromo P450, um dos possíveis mecanismos de toxicidade hepática e renal promovida por esses compostos. O objetivo deste estudo foi determinar os níveis de substâncias reativas ao ácido tiobarbitúrico (SRAT), como indicador da peroxidação lipídica, em ratos que receberam sevoflurano, previamente tratados ou não com isoniazida, indutor enzimático do citocromo P450 2E1. MÉTODO: Foram utilizados 42 animais, distribuídos aleatoriamente em 4 grupos que receberam respectivamente: G1 - oxigênio a 100% 1 l.min-1/60 minutos por 5 dias consecutivos; G2 - sevoflurano a 4% em oxigênio a 100%, 1 l.min-1/60 minutos por 5 dias consecutivos; G3 - isoniazida (50 mg.kg-1.dia) por via intraperitoneal durante 4 dias consecutivos, em seguida foi tratado como o G1, no G4 - isoniazida 50 mg.kg-1.dia por via intraperitoneal durante 4 dias consecutivos, sendo tratado, posteriormente, como o G2. Após 12 horas do último tratamento, sacrificaram-se os animais e foi coletado o plasma para a análise das SRAT, sendo removido o lobo esquerdo do fígado e os rins para exame histológico. RESULTADOS: Os resultados mostraram aumento nas taxas de SRAT no G3 e G4, com elevação discreta em G2. O estudo histológico revelou necrose focal no fígado de ratos pré-tratados com isoniazida (G3). CONCLUSÕES: O sevoflurano promoveu peroxidação lipídica apenas quando associado à isoniazida.

Palavras-chave

ANESTÉSICOS, ANESTÉSICOS, ANIMAL, DROGAS, METABOLISMO

Abstract

BACKGROUND AND OBJECTIVES: Sevoflurane is a fluorinated ether with low blood solubility and biotransformed by an oxidative enzymatic liver system involving cytochrome P450 2E1. Lipid peroxidation occurs during ethers biotransformation process under action of cytochrome P450, a possible mechanism for liver and kidney toxicity promoted by such compounds. This study aimed at determining the levels of substances reactive to thiobarbituric acid (TBARS), as an index for lipid peroxidation in sevoflurane-treated rats, previously treated or not with isoniazid, enzymatic inducer of cytochrome P450 2E1. METHODS: Forty two male Wistar rats were randomly distributed in 4 groups receiving respectively: G1 - 1 L.min-1/60 minutes of 100% oxygen for 5 consecutive days; G2 - 4% sevoflurane in 1 L.min-1/60 minutes of 100% oxygen for 5 consecutive days; G3 - intraperitoneal isoniazid (50 mg.kg-1/day) for 4 consecutive days and then treated as G1; G4 - intraperitoneal isoniazid (50 mg.kg-1/day) for 4 consecutive days and then treated as G2. Animals were sacrificed 12 hours after the last treatment, plasma was collected for TBARS analysis and the liver left lobe and both kidneys were removed for histological evaluation. RESULTS: Results have shown increased TBARS levels in G3 and G4, with mild increase in G2. Histological evaluation has revealed focal liver necrosis in rats pretreated with isoniazid (G3). CONCLUSION: Sevoflurane has promoted lipid peroxidation only when associated to isoniazid.

Keywords

ANESTHETICS, ANESTHETICS, ANIMAL, DRUGS, METABOLISM

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