Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/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

Referencias

Ferreira ALA, Matsubara SL. Radicais livres: conceitos, doenças relacionadas, sistema de defesa e estresse oxidativo. Rev Ass Med Brasil. 1997;43:61-68.

Durak I, Guven T, Birey M. Halothane hepatotoxicity and hepatic free radical metabolism in guinea pigs: the effects of vitamin E. Can J Anaesth. 1996;43:741-748.

Durak I, Ozturk HS, Dikmen B. Isoflurane impairs antioxidant defence system in guinea pig kidney. Can J Anaesth. 1999;46:797-802.

Delfino J, Vale NB, Magalhães E. Estudo comparativo entre sevoflurano e halotano para cirurgia pediátrica de curta duração. Rev Bras de Anestesiol. 1997;47:10-15.

Goa KL, Noble S, Spencer CM. Sevoflurane in paediatric anaesthesia: a review. Paediatr Drugs. 1999;1:127-153.

Kenna JG, Jones RM. The organ toxicity of inhaled anesthetics. Anesth Analg. 1995;81(^sS51-S66).

Shayiq RM, Raza H, Kidwai AM. Fluoride and lipid peroxidation: a comparative study in different rat tissues. Bull Environ Contam Toxicol. 1986;37:70-76.

Dai Y, Rashba-Step J, Cederbaum AI. Stable expression of human cytochrome P4502E1 in HepG2 cells: characterization of catalytic activities and production of reactive oxygen intermediates. Biochemistry. 1993;32:6928-6937.

Bernheim F, Bernheim MLC, Wilbur KM. The reaction between thiobarbituric acid and the oxidation products of certain lipids. J Biol Chem. 1948;174:257-264.

Sato N, Fujii K, Yuge O. In vivo and in vitro sevoflurane-induced lipid peroxidation in guinea-pig liver microsomes. Pharmacol Toxicol. 1994;75:366-370.

Kundu D, Hallinan T. Fluoride or GTP-gamma-S markedly stimulate lipid peroxidation catalysed by endogenous iron in rat liver microsomes. Biochem Soc Trans. 1995;23:541S.

Ekstrom G, Ingelman-Sundberg M. Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450llE1). Biochem Pharmacol. 1989;38:1313-1319.

Arimoto T, Yoshikawa T, Takano H. Generation of reactive oxygen species and 8-hydroxy-2´-deoxyguanosine formation from diesel exhaust particle components in L1210 cells. Jpn J Pharmacol. 1999;80:49-54.

Wang J, Zeng YM, Li H. Effects of sevoflurane and halothane on contracture function, SOD activity, MDA content on isolated ischemic rat hearts. Anesthesiology. 1997;87:3A.

Allaouchiche B, Debon R, Goudable J. Oxidative stress status during exposure to propofol, sevoflurane and desflurane. Anesth Analg. 2001;93:981-985.

Wood CL, Gandolfi AJ, Van Dyke RA. Lipid biding of a halothane metabolite. Relationship to lipid peroxidation in vitro. Drug Metab Dispos. 1976;4:305-313.

Naziroglu M, Gunay C. The levels of some antioxidant vitamins, glutathione peroxidase and lipoperoxidase during anaesthesia of dogs. Cell Biochem Funct. 1999;17:207-212.

Tsuchiya M, Asada A, Kasahara E. Antioxidant protection of propofol and its recycling in erythrocyte membranes. Am J Respir Crit Care Med. 2002;165:54-60.

Kang MY, Tsuchiya M, Packer L. In vitro study on antioxidant potential of various drugs used in the perioperative period. Acta Anaesthesiol Scand. 1998;42:4-12.

Kharasch ED, Frink EJ, Artru A. Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function. Anesth Analg. 2001;93:1511-1520.

Timbrell JA, Mitchell JR, Snodgrass WR. Isoniazid hepatotoxicity: the relationship between covalent binding and metabolism in vivo. J Pharmacol Exp Ther. 1980;213:364-369.

Mitchell JR, Zimmerman HJ, Ishak KG. Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. Ann Intern Med. 1976;84:181-192.

Rice SA, Sbordone L, Mazze RI. Metabolism by rat hepatic microsomes of fluorinated ether anesthetics following isoniazida administration. Anesthesiology. 1980;53:489-493.

Walubo A, Smith P, Folb PI. The role of oxygen free radicals in isoniazida-induced hepatotoxicity. Methods Find Exp Clin Pharmacol. 1998;20:649-655.

Sarich TC, Zhou T, Adams SP. A model of isoniazid-induced hepatotoxicity in rabbits. J Pharmacol Toxicol Methods. 1995;34:109-116.

Bermejo-Alvarez MA, Rodrigues-Dintén MJ, Brime-Casanueva JI. Efectos renales de la anestesia prolongada com sevoflurane en ratas Wistar. Rev Esp Anestesiol Reanim. 1999;46:241-246.

Yesilkaya A, Ertug Z, Yegin A. Deformability and oxidant stress in the red blood cells under the influence of halothane and isoflurane anesthesia. Gen Pharmacol. 1998;31:33-36.

Saralakumari D, Rao PR. Erythrocyte glutathione metabolism in human chronic fluoride toxicity. Biochem Int. 1991;23:349-357.

Luzzatto L, Mehta A. The Metabolic Basis of Inherited Disease. 1995:225-229.

Gentz BA, Malan TP. Renal toxicity with sevoflurane: a storm in a teacup?. Drugs. 2001;61:2155-2162.

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