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The Effects of Thiopenthone Sodium and Propofol on Rat Liver

Year 2014, Volume: 5 Issue: 2, 36 - 44, 30.08.2014

Abstract

Aim: This study was conducted to investigate the histopathological and biochemical effects of propofol and sodium thiopental, which are intravenous anaesthetics used in surgical operations on rat liver.
Material–Method: There were three study groups each consisting of nine animals: Control (n=9), propofol (n=9) and sodium thiopental (n=9) group. Propofol (20 mg / kg / day, i.p) and sodium thiopental (60 mg / kg / day, i.p) were administered with one day interval for 20 days.
Findings: At the end of the study, liver tissues were taken for histological examination and for biochemical analysis. There was a significantly increase in MDA level in propofol exposed group, when compared with the controls and this was statistically significant. We found significant damage in histological sections in paralel to biochemical findings. These histological changes hepatocyte degeneration, vascular congestion and mononuclear cell infiltration in different sites and bile duct proliferation observed in propofol and this was statistically significant. MDA levels were significantly increased in sodium thiopental given group. Also, SOD and CAT activities were prominent in this group. Also, more histological changes like hepatocyte degeneration, vascular congestion and mononuclear cell infiltration in different sites were observed in sodium thiopental and this was statistically significant.
Results: As a result, we can say that these intravenous anaesthetic agents may cause dose dependent damage in liver tissue. For this reason, we think that one must take care of the administration duration and dose levels of the anaesthetics during surgical operations.


Key Words: Propofol, Thiopental sodium, liver, oxidative damage.

References

  • Reves JG, Flezzani P, Kissin I. Pharmacology of Anesthetic Induction Drugs. Cardiac Anesthesia. Kaplan SA (ed) 2 nd Ed. Grune and Stratton Inc. Orlando 1987.
  • Trevor AJ, Miller RD. General Anesthetics. Basic and Clinical Pharmacology. Ed. Katzung Bg. 7 th Ed. Connecticut, Appleton & Lange, 1998: 409-423.
  • Aitkenhead AR, Smith G (editor). Intravenous Anesthetic Agents.texbook of Anesthesia. 2 nd Ed. Churchil Livingstone edinburgh, 1990.
  • Rang, H.P., Dale, M.M., Ritter, J.M., Gardner, P., 1995. General Anesthetic Agents. Pharmacology. 3 th Ed. Churchil Livingstone, New York. Inc., 532-547.
  • Sear JW. Toxicity of Intravenous Anaesthetics. British Journal of Anaesthesia, 1987; 59: 24-45.
  • Marshall BE, Longnecker DE. General Anesthetics. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Eds. In Chief: Hardman JG, Limbird LE. 9 th Ed. New York, The McGraw-Hill Companies, İnc. 1996: 307-329.
  • Song D, Chung F, Wong J, et al. The Assesment of Postural Stability after Ambulatory Anesthesia: A Comparison of Desflurane with Propofol. Anesth Analg. 2002; 94: 60-64.
  • Angelini G, Ketzler JT, Coursin DB. Use of Propofol and Other Non-Benzodiazepine Sedatives in the Intensive Care Unite. Crit Care Clin. 2000; 17: 863-880.
  • Collins VJ. Principles of Anesthesiology: General and Regional Anesthesia. 3 rd Ed. Pennsylvania. Lea & Febiger 1993; 651-786.
  • Barash PG, Cullen BF, Stoelting RK. Clinical Anesthesia. Phladelphia. JP Lippincott 1989: 227-53.
  • Dundee LW. Intravenous Anesthesia. 2 nd Ed. Hong kong Longman Group, 1988: 160-183.
  • Reves JG, Glass PSA, Lubarsky DA. Nonbarbiturade Intravenous Anesthetics. In:Miller RD. Ed. Anesthesia, 5 th Ed. New York, Churchil Livingstone, 1999: 228-72.
  • Aun CST,. New Intravenous Agents. Br J anaesth 1999; 83: 29-41.
  • Leuwer M, Haeseler G. Interaction of Phenol Derivatives with Ion channels. Eur J Anaesth. 2002; 19: 1-8.
  • Friederich P, Benzenberg D, Urban BW. Ketamine and Propofol Differently Inhibit Human Neuronal K+ Channels. Eur J Anaesth. 2002; 18: 177-183.
  • Yamazaki M, Nagakawa T,Hatakeyama N, et al. The Effects of Propofol on Neuronal and Endothelial Control of Insitu Rat Mesenteric Vascular Smooth Muscle Transmembrane Potentials. Anesth Analg. 2002; 94: 892- 897.
  • Kushikata T, Hirota K, Yoshida H, et al. Alpha-2 Adrenireceptor Activity Affects Propofol- Induced Sleep Time. Anesth Analg. 2002; 201-206.
  • Okutomi T, Nomto K, Nakamura K, Goto F. Autogenous Production of Hydroxyl Radicals From Thiopental. Acta Anaesthesiol Scand. 1995; 39(3): 338-342.
  • Abidova, S.S. The Effects of Propofol and Ketamine on the Lipid Metabolism and Peroxidation in Rats. Klinicheskaya Farmakologiya, 2002; 65(6): 48.
  • Salman H, Bergman M, Bessler H, Alexandrova S, Beilin B, Djaldetti M. Effect of Sodium Thiopentone Anesthesia on the Phagocytic Activity of Rat Peritoneal Macrophages. Life Science, 1998; 63(25): 2221-2226.
  • Lowry OH, Rosenbrough NJ, Farr AL, Radall RJ. Protein Measurement with the Folin Phenol Reagent. J Biol Chem. 1951; 193: 265-275.
  • Drapper HH, Hadley M. Melondialdehyde Determination as Index of Lipid Peroxidation. Methods Enzymol. 1990; 186: 421-431.
  • Sun Y, Oberley LW, Ying L. A Simple Method for Clinical Assay of Superoxide Dismutase. Clin Chem. 1988; 34: 497-500.
  • Aebi Y. Catalase in vitro. Methods Enzymol. 1984; 105: 121-126.
  • Abdel-Wahhab MA, Nada SA, Arbid MS. Ochratoxicosis: Preventation of Developmental Toxicity by L-Methionine in Rats. J Applied Toxicol. 1999; 19: 7-12.
  • Fee JPH, McCaugghey W. Clarke RSJ, Wllace WFM. Sedative Drugs. In: Anaesthetic Physiology and Pharmacology. Churchill Livingston, New York. 1997; 191- 206.
  • Stephen B, Kyle L, Yong X, Cynthia A, Donald E, Earl F, James E. Role of Oxidative Stres in the :Mechanism of Dieldrin’s Hepatotoxicity. Annals of Clinical and Laboratory Science. 1997; 27(3): 196-208.
  • Spallholz JE. Selenium and Glutation Peroxidase: Essential Nutritient and Antioxidant Component of the Immun System. Adv. Exp. Med. Biol. 1990; 262: 145-158.
  • Özcan O, Karaöz E, Sarsılamz M, Ozan H, Sınav A, Oba G. Sıçanlarda Karbontetraklorür Hepatotoksisitesine Karşı E Vitamininin Etkisi. Doğa Tr J of Medical Sci. 1992; 16: 45-54.
  • Bleecker J, Lison D, Abeele KV, Willems J, Reuck J. Acut and Subacut Orgnophosphate Poisoning in Rat. Neuro Toxicology. 1994; 15(2): 341-348.
  • Bushnell PJ, Kelly KL, Ward TR. Repeated Inhibition of Cholinesterase by Chorpyrifos in Rats: Behavioral, Neurochemical and Phamacological Indices of Tolerance. J. Pharmacol Exp Ther. 1994; 270(1): 15-25.
  • Niwa Y, Ishimato K, Kanoh T. Induction of Superoxide Dismutase in Leukocytes by Paraquat: Correlation with Age and Possible Predictor of Longevity. Blood. 1990; 76: 835-841.
  • The Effect of Propofol Anesthesia on Free Radical-Induced Lipid Peroxidation in the Rat Liver. Eur J Anaesthesiol. 1993; 10(4): 261-266.
  • Bao YP, Williamson G, Tew D, Plumb GW, Lambert N, Jones JG, Menon DK. Antioxidant Effects of Propofol in Human Hepatic Microsomes: Concentration Effects and Clinical Relevance. British Journal of Anaesthesia, 1998; 81(4): 584
  • Salman H, Bergman M, Bessler H, Alexandrova S, Beilin B, Djaldetti M. Effect of Sodium Thiopentone Anesthesia on the Phagocytic Activity of Rat Peritoneal Macrophages. Life Science, 1998; 63(25): 2221-2226.
  • Bjorkman S, Redke F. Clearance of Fentanyl, Alfentanil, Methohexitone, Thiopentone and Ketamine in Relation to Estimated Hepatic Blood Flow in Several Animal Species : Application to Prediction of Clearance in man. J Pharm Pharmacol. 2000; 52(12): 203-204.
  • Novelli GP, Marsili M, Lorenzi P. Influence of Liver Metabolism on the Actions of Althesin and Thiopentone. Br. J Anaesth. 1975; 47(9): 913-916.
  • Blunnie WP, Zacharias M, Dundee JW, et al. Liver Enzyme Studies with Continuous Intravenous Anaesthesia. Anahesthesia, 1981; 36(2): 152-156.
  • Fassoulaki A, Andreopoulou K, Williams G, Pateras CH. The Effect of Single and Repeated Doses of Thiopentone and Fentanyl on Liver Function in the Rat. Anahesthesiaand Intensive Care. 1986; 14(2): 145-147.
  • Chen TL, Wu CH, Chen TG, Tai YT, Chang HC, Lin CJ. Effects of Propofol on Functional Activities of Hepatic and Extrahepatic Conjugation Enzyme Systems. British Journal of Anaesthesia, 2000; 84(6): 771.

Sıçan Karaciğeri Üzerine Tiyopental Sodyum ve Propofolün Etkileri

Year 2014, Volume: 5 Issue: 2, 36 - 44, 30.08.2014

Abstract

Amaç: Bu çalışma sıçan karaciğeri üzerine cerrahi operasyonlarda kullanılan intravenöz anestezik ajanlardan propofol ve tiyopental sodyumun histopatolojik ve biyokimyasal etkilerini incelemek amacıyla yapılmıştır.
Materyal Metod: Deney grupları kontrol (n=9), propofol (n=9) ve tiyopental sodyum (n=9) şeklinde gruplandırılmıştır. Propofol (20 mg / kg / gün, ip) ve tiyopental sodyum (60 mg / kg / gün, ip) bir gün ara ile 20 gün boyunca uygulanmıştır.
Bulgular: Çalışmanın sonunda, karaciğer dokuları histopatolojik ve biyokimyasal analizler için alınmıştır. Propofol verilen grup, kontrol grubu ile karşılaştırıldığında Malondialdehit (MDA) düzeyinin istatistiksel olarak anlamlı bir artış gösterdiği görülmüştür. Biyokimyasal bulgulara paralel olarak histolojik kesitlerde de önemli yapısal değişiklikler gözlenmiştir. Bu değişiklikler, hepatosit dejenerasyonu, vasküler konjesyon, mononükleer hücre infiltrasyonu ve safra kanalı proliferasyonu şeklindedir. Tiyopental sodyum uygulanan grupta da MDA düzeylerinde anlamlı bir artış gözlenmiştir. Superoksit Dismutaz (SOD) ve Katalaz (CAT) aktivite değerleri hem propofol hem de tiyopental sodyum grubunda artış göstermiştir. Dolayısıyla bu gruplarda oluşan antioksidan savunma sistemi MDA'nın yükselmesi ile lipit peroksidatif hasarı engelleyememiştir. Ayrıca, tiyopental sodyum grubunda da hepatosit dejenerasyonu, vasküler konjesyon ve mononükleer hücre infiltrasyonu gibi histolojik değişiklikler gözlenmiştir.
Sonuç: Sonuç olarak bu intravenöz anestezik ajanların doza bağlı olarak karaciğer dokusunda hasar meydana getirdiğini söyleyebiliriz. Bu nedenle ameliyatlarda kullanılırken dozuna ve uygulama süresine dikkat edilmesi gerektiğini düşünmekteyiz.


Anahtar Kelimeler: Propofol, Tiyopental sodyum, karaciğer, osdidatif hasar

References

  • Reves JG, Flezzani P, Kissin I. Pharmacology of Anesthetic Induction Drugs. Cardiac Anesthesia. Kaplan SA (ed) 2 nd Ed. Grune and Stratton Inc. Orlando 1987.
  • Trevor AJ, Miller RD. General Anesthetics. Basic and Clinical Pharmacology. Ed. Katzung Bg. 7 th Ed. Connecticut, Appleton & Lange, 1998: 409-423.
  • Aitkenhead AR, Smith G (editor). Intravenous Anesthetic Agents.texbook of Anesthesia. 2 nd Ed. Churchil Livingstone edinburgh, 1990.
  • Rang, H.P., Dale, M.M., Ritter, J.M., Gardner, P., 1995. General Anesthetic Agents. Pharmacology. 3 th Ed. Churchil Livingstone, New York. Inc., 532-547.
  • Sear JW. Toxicity of Intravenous Anaesthetics. British Journal of Anaesthesia, 1987; 59: 24-45.
  • Marshall BE, Longnecker DE. General Anesthetics. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Eds. In Chief: Hardman JG, Limbird LE. 9 th Ed. New York, The McGraw-Hill Companies, İnc. 1996: 307-329.
  • Song D, Chung F, Wong J, et al. The Assesment of Postural Stability after Ambulatory Anesthesia: A Comparison of Desflurane with Propofol. Anesth Analg. 2002; 94: 60-64.
  • Angelini G, Ketzler JT, Coursin DB. Use of Propofol and Other Non-Benzodiazepine Sedatives in the Intensive Care Unite. Crit Care Clin. 2000; 17: 863-880.
  • Collins VJ. Principles of Anesthesiology: General and Regional Anesthesia. 3 rd Ed. Pennsylvania. Lea & Febiger 1993; 651-786.
  • Barash PG, Cullen BF, Stoelting RK. Clinical Anesthesia. Phladelphia. JP Lippincott 1989: 227-53.
  • Dundee LW. Intravenous Anesthesia. 2 nd Ed. Hong kong Longman Group, 1988: 160-183.
  • Reves JG, Glass PSA, Lubarsky DA. Nonbarbiturade Intravenous Anesthetics. In:Miller RD. Ed. Anesthesia, 5 th Ed. New York, Churchil Livingstone, 1999: 228-72.
  • Aun CST,. New Intravenous Agents. Br J anaesth 1999; 83: 29-41.
  • Leuwer M, Haeseler G. Interaction of Phenol Derivatives with Ion channels. Eur J Anaesth. 2002; 19: 1-8.
  • Friederich P, Benzenberg D, Urban BW. Ketamine and Propofol Differently Inhibit Human Neuronal K+ Channels. Eur J Anaesth. 2002; 18: 177-183.
  • Yamazaki M, Nagakawa T,Hatakeyama N, et al. The Effects of Propofol on Neuronal and Endothelial Control of Insitu Rat Mesenteric Vascular Smooth Muscle Transmembrane Potentials. Anesth Analg. 2002; 94: 892- 897.
  • Kushikata T, Hirota K, Yoshida H, et al. Alpha-2 Adrenireceptor Activity Affects Propofol- Induced Sleep Time. Anesth Analg. 2002; 201-206.
  • Okutomi T, Nomto K, Nakamura K, Goto F. Autogenous Production of Hydroxyl Radicals From Thiopental. Acta Anaesthesiol Scand. 1995; 39(3): 338-342.
  • Abidova, S.S. The Effects of Propofol and Ketamine on the Lipid Metabolism and Peroxidation in Rats. Klinicheskaya Farmakologiya, 2002; 65(6): 48.
  • Salman H, Bergman M, Bessler H, Alexandrova S, Beilin B, Djaldetti M. Effect of Sodium Thiopentone Anesthesia on the Phagocytic Activity of Rat Peritoneal Macrophages. Life Science, 1998; 63(25): 2221-2226.
  • Lowry OH, Rosenbrough NJ, Farr AL, Radall RJ. Protein Measurement with the Folin Phenol Reagent. J Biol Chem. 1951; 193: 265-275.
  • Drapper HH, Hadley M. Melondialdehyde Determination as Index of Lipid Peroxidation. Methods Enzymol. 1990; 186: 421-431.
  • Sun Y, Oberley LW, Ying L. A Simple Method for Clinical Assay of Superoxide Dismutase. Clin Chem. 1988; 34: 497-500.
  • Aebi Y. Catalase in vitro. Methods Enzymol. 1984; 105: 121-126.
  • Abdel-Wahhab MA, Nada SA, Arbid MS. Ochratoxicosis: Preventation of Developmental Toxicity by L-Methionine in Rats. J Applied Toxicol. 1999; 19: 7-12.
  • Fee JPH, McCaugghey W. Clarke RSJ, Wllace WFM. Sedative Drugs. In: Anaesthetic Physiology and Pharmacology. Churchill Livingston, New York. 1997; 191- 206.
  • Stephen B, Kyle L, Yong X, Cynthia A, Donald E, Earl F, James E. Role of Oxidative Stres in the :Mechanism of Dieldrin’s Hepatotoxicity. Annals of Clinical and Laboratory Science. 1997; 27(3): 196-208.
  • Spallholz JE. Selenium and Glutation Peroxidase: Essential Nutritient and Antioxidant Component of the Immun System. Adv. Exp. Med. Biol. 1990; 262: 145-158.
  • Özcan O, Karaöz E, Sarsılamz M, Ozan H, Sınav A, Oba G. Sıçanlarda Karbontetraklorür Hepatotoksisitesine Karşı E Vitamininin Etkisi. Doğa Tr J of Medical Sci. 1992; 16: 45-54.
  • Bleecker J, Lison D, Abeele KV, Willems J, Reuck J. Acut and Subacut Orgnophosphate Poisoning in Rat. Neuro Toxicology. 1994; 15(2): 341-348.
  • Bushnell PJ, Kelly KL, Ward TR. Repeated Inhibition of Cholinesterase by Chorpyrifos in Rats: Behavioral, Neurochemical and Phamacological Indices of Tolerance. J. Pharmacol Exp Ther. 1994; 270(1): 15-25.
  • Niwa Y, Ishimato K, Kanoh T. Induction of Superoxide Dismutase in Leukocytes by Paraquat: Correlation with Age and Possible Predictor of Longevity. Blood. 1990; 76: 835-841.
  • The Effect of Propofol Anesthesia on Free Radical-Induced Lipid Peroxidation in the Rat Liver. Eur J Anaesthesiol. 1993; 10(4): 261-266.
  • Bao YP, Williamson G, Tew D, Plumb GW, Lambert N, Jones JG, Menon DK. Antioxidant Effects of Propofol in Human Hepatic Microsomes: Concentration Effects and Clinical Relevance. British Journal of Anaesthesia, 1998; 81(4): 584
  • Salman H, Bergman M, Bessler H, Alexandrova S, Beilin B, Djaldetti M. Effect of Sodium Thiopentone Anesthesia on the Phagocytic Activity of Rat Peritoneal Macrophages. Life Science, 1998; 63(25): 2221-2226.
  • Bjorkman S, Redke F. Clearance of Fentanyl, Alfentanil, Methohexitone, Thiopentone and Ketamine in Relation to Estimated Hepatic Blood Flow in Several Animal Species : Application to Prediction of Clearance in man. J Pharm Pharmacol. 2000; 52(12): 203-204.
  • Novelli GP, Marsili M, Lorenzi P. Influence of Liver Metabolism on the Actions of Althesin and Thiopentone. Br. J Anaesth. 1975; 47(9): 913-916.
  • Blunnie WP, Zacharias M, Dundee JW, et al. Liver Enzyme Studies with Continuous Intravenous Anaesthesia. Anahesthesia, 1981; 36(2): 152-156.
  • Fassoulaki A, Andreopoulou K, Williams G, Pateras CH. The Effect of Single and Repeated Doses of Thiopentone and Fentanyl on Liver Function in the Rat. Anahesthesiaand Intensive Care. 1986; 14(2): 145-147.
  • Chen TL, Wu CH, Chen TG, Tai YT, Chang HC, Lin CJ. Effects of Propofol on Functional Activities of Hepatic and Extrahepatic Conjugation Enzyme Systems. British Journal of Anaesthesia, 2000; 84(6): 771.
There are 40 citations in total.

Details

Primary Language English
Journal Section Original Article
Authors

DİLEK Bayram

MERAL Öncü This is me

NURTEN Özçelik

HACI Yılmaz This is me

EFKAN Uz This is me

ALPASLAN Gökçimen

MELTEM Özgöçmen

Publication Date August 30, 2014
Submission Date December 10, 2013
Published in Issue Year 2014 Volume: 5 Issue: 2

Cite

Vancouver Bayram D, Öncü M, Özçelik N, Yılmaz H, Uz E, Gökçimen A, Özgöçmen M. The Effects of Thiopenthone Sodium and Propofol on Rat Liver. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2014;5(2):36-44.

SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.