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Protective role of zinc pretreatment in hepatotoxicity induced by halothane

Published online by Cambridge University Press:  01 October 2008

C. Unsal
Affiliation:
Selcuk University, Meram Medical Faculty, Department of Anesthesiology and Reanimation, Konya, Turkey
J. B. Celik*
Affiliation:
Selcuk University, Meram Medical Faculty, Department of Anesthesiology and Reanimation, Konya, Turkey
H. Toy
Affiliation:
Selcuk University, Meram Medical Faculty, Department of Pathology, Konya, Turkey
H. Esen
Affiliation:
Selcuk University, Meram Medical Faculty, Department of Pathology, Konya, Turkey
S. Otelcioglu
Affiliation:
Selcuk University, Meram Medical Faculty, Department of Anesthesiology and Reanimation, Konya, Turkey
*
Correspondence to: Jale Bengi Celik, Department of Anesthesiology, Meram Medical Faculty, Selcuk University, 42080 Konya, Turkey. E-mail: celikcet@hotmail.com; Tel: +533 5656838; Fax: +90 0332 223 6181
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Summary

Background and objective

This study was designed to determine the protective effects of zinc on halothane-induced hepatotoxicity.

Methods

Forty-five male Sprague-Dawley rats were divided into three groups. The halothane group received normal drinking water and diet; the zinc-halothane group received 227 mg L−1 zinc sulphate in the drinking water and diet for 2 weeks; and the control group received normal diet and water. At the end of 2 weeks, rats were housed in an anaesthesia box and 1 MAC (minimum alveolar concentration) halothane was administered at 6 L min−1 in room air for 2 h. This was repeated 48 h later. After the rats were sacrificed, we measured alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, glutathione-S-transferase, serum electrolytes and bilirubin in samples. The degree of liver toxicity was assessed by light microscopic examination.

Results

We demonstrated a reduction of alanine aminotransferase, aspartate amino transferase, glutathione-S-transferase levels and a reduction in liver damage in the zinc-halothane group.

Conclusion

The study concludes that zinc has the potential to alleviate the toxic effects of halothane in rat liver.

Type
Original Article
Copyright
Copyright © European Society of Anaesthesiology 2008

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References

1.Yamada, T, Nomura, T, Miki, Y, Kanda, S, Sasaki, J. Histochemical and immunohistochemical changes in rat hepatocytes after halothane exposure. J Anesth 2002; 16: 138144.CrossRefGoogle ScholarPubMed
2.Schimidt, CC, Suttner, SW, Piper, SN, Nagel, D, Blodt, J. Comparison of the effects of desflurane and isoflurane anaesthesia on hepatocellular function assessed by alpha glutathione S-transferase. Anaesthesia 1999; 54: 12041219.Google Scholar
3.Sidhu, P, Garg, ML, Morgenstern, P, Vogt, J, Butz, T, Dhawan, DK. Role of regulating the levels of hepatic elements following nickel toxicity in rats. Biol Trace Elem Res 2004; 102: 161172.CrossRefGoogle ScholarPubMed
4.Bettger, JW, O’Dell, BL. Critical physiological role of zinc in the structure and function of biomembranes. Life Sci 1981; 28: 14251438.CrossRefGoogle ScholarPubMed
5.Sidhu, P, Garg, ML, Dhawan, DK. Protective role of zinc in nickel induced hepatotoxicity in rats. Chem Biol Interact 2004; 150: 199209.CrossRefGoogle ScholarPubMed
6.Odaka, Y, Takahashi, T, Yamasaki, A et al. Prevention of halothane induced hepatotoxicity by hemin pretreatment. Biochem Pharmacol 2000; 59: 871880.CrossRefGoogle ScholarPubMed
7.Warholm, M, Guttenberg, C, Bohr, CV, Mannervik, B. Glutathione S transferase from human liver. Methods Enzymol 1985; 113: 499504.CrossRefGoogle ScholarPubMed
8.Elliot, RH, Strunin, L. Hepatotoxicity of anaesthetics. Br J Anaesth 1993; 70: 339348.CrossRefGoogle Scholar
9.Benjamin, SB, Goodman, ZD, Ishak, KG, Zimmerman, HJ, Irey, NS. The morphologic spectrum of halothane induced hepatic injury. Analysis of 77 cases. Hepatology 1985; 5: 11631171.CrossRefGoogle ScholarPubMed
10.Ray, DC, Drummond, GB. Halothane hepatitis. Br J Anaesth 1991; 67: 8499.CrossRefGoogle ScholarPubMed
11.Dhawan, D, Goel, A, Gautam, CS. Effects of zinc intake on liver enzymes in toxicity carbon tetrachloride induced liver injury. Med Sci Res 1992; 20: 5556.Google Scholar
12.Dhawan, DK, Goel, A. Protective role of zinc on rat liver function in long term toxicity induced by carbon tetrachloride. J Trace Elem Exp Med 1994; 7: 19.Google Scholar
13.Vanhaecke, T, Lindros, KO, Oinonen, T, Vercrusse, A, Rogiers, V. Effect of long-term Ethanol exposure on the acinar distribution of hepatic glutathione S-transferase. Drug Metab Dispos 2000; 28: 14701474.Google ScholarPubMed
14.Ahmed, S, Rahman, A, Saleem, M, Athar, M, Sultana, S. Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress. Hum Exp Toxicol 1999; 18: 691698.CrossRefGoogle ScholarPubMed
15.Kharasch, DC, Hankins, K, Fenstamaker, K, Cox, K. Human halothane metabolism, lipid peroxidation, and cytochromes P4502A6 and P4503A4. Eur J Clin Pharmacol 2000; 55: 853859.CrossRefGoogle ScholarPubMed
16.Sharp, JH, Trudell, JR, Cohen, EN. Volatile metabolites and decomposition products of halothane in man. Anesthesiology 1979; 50: 28.CrossRefGoogle ScholarPubMed
17.Johnson, ME, Sill, JC, Uhl, CB, Van Dyke, RA. Effect of halothane on hypoxic toxicity and Glutathione status in cultured rat hepatocytes. Anesthesiology 1993; 79: 10611065.CrossRefGoogle ScholarPubMed
18.Schieble, TM, Costa, AK, Heffel, DF, Trudell, JR. Comparative toxicity of halothane, isoflurane, hypoxia and phenobarbital induction in monolayer cultures of rats hepatocytes. Anesthesiology 1988; 68: 485494.CrossRefGoogle Scholar
19.de Groot, H, Noll, T. Halothane hepatotoxicity: relation between metabolic activation, hypoxia, covalent binding, lipid peroxidation and liver cell damage. Hepatology 1983; 3: 601606.CrossRefGoogle ScholarPubMed
20.Stehbens, WE. Oxidative stress, toxic hepatitis, and antioxidants with particular emphasis on zinc. Exp Mol Pathol 2003; 75: 265276.CrossRefGoogle ScholarPubMed
21.Sato, N, Fujii, K, Yuge, O, Morio, M. The association of halothane-induced lipid peroxidation with the anaerobic metabolism of halothane: an in vitro study in guinea pig liver microsomes. Hiroshima J Med Sci 1990; 39: 16.Google Scholar
22.Awad, JA, Horn, J-L, IIRoberts, J, Franks, JJ. Demonstration of halothane-induced hepatic lipid peroxidation in rats by quantification of F2-isoprotones. Anesthesiology 1996; 84: 910916.CrossRefGoogle Scholar
23.Minoda, Y, Kharasch, ED. Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6). Anesthesiology 2001; 95: 509514.CrossRefGoogle ScholarPubMed
24.Dhawan, DK, Goel, A. Further evidence for zinc as a hepatoprotective agent in rat liver toxicity. Exp Mol Pathol 1996; 63: 110117.CrossRefGoogle Scholar
25.Leonard, TB, Hewit, WR, Dent, JG, Morgan, DG. Serum alanine aminotransferase (ALT) as a quantitative indicator of hepatocyte necrosis. Toxicologist 1986; 6: 184188.Google Scholar