Yüksek dozda parasetamolün dişi sıçanların tiroid bezi üzerine olumsuz etkileri
Year 2020,
, 311 - 319, 03.12.2020
Banu Eren
,
Sare Ulubay
,
Dilek Sağır
,
Burcu Demirel Yılmaz
,
Sevcan Mercan
Abstract
Amaç: Bu çalışmanın amacı, etki mekanizması henüz tam olarak bilinmeyen ancak bilinçsizce kullanılan bir analjezik olan parasetamolün tiroid bezi üzerinde toksisiteye neden olup olmadığını belirlemektir.
Gereç ve Yöntem: Toplam 25 adet dişi Wistar albino rat kontrol (K), Parasetamol 7 gün (P7), parasetamol 14 gün (P14), Parasetamol 21 gün (P21) ve parasetamol 28 gün (P28) olarak 5 gruba ayrıldı. Parasetamol gruplarındaki sıçanlara sakrifiye edilecekleri güne kadar gavaj ile 750 mg/kg/gün parasetamol verildi. Çıkarılan tiroid bezlerine rutin histolojik prosedürler uygulandı. Tiroid dokusu kesitleri morfometrik ve histopatolojik olarak değerlendirildi.
Bulgular: Parasetamol verilen grupların tiroid dokusu kesitlerinde folikül epitel hücrelerinde sitoplazmik vakuolizasyon, folikül ve kolloid yapılarında bozulma saptandı. P7 grubuna ait folikül çap ölçümü ortalaması kontrol grubuna kıyasla anlamlı azaldı (p<0,05). Tüm parasetamol gruplarında folikül epitel yüksekliği ortalaması kontrol grubuna kıyasla anlamlı olarak arttı (p<0.05).
Sonuç: Bu sonuçlar, yüksek dozda parasetamolün kullanım süresine bağlı olarak tiroid bezi üzerinde toksik etkilere neden olduğunu göstermektedir.
Supporting Institution
Ondokuz Mayıs Üniversitesi
Project Number
PYO.FEN.1904.15.001
Thanks
Ondokuz Mayıs Üniversitesi Proje Yönetim Ofisi Koordinatörlüğü’ne destekleri için teşekkür ederiz.
References
- Ajith TA, Hema U, Aswathy MS. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status, Food Chem Toxicol. 2007; 45(11):2267-72.
- Emet M, Yayla M. Asetaminofen (Parasetamol) Zehirlenmesi. Turkiye Klinikleri J Emerg Med-Special Topics. 2016; 2.1: 51-7.
- Küçükardalı ,Cinan, U, Acar HV, Özkan S, Top C, Nalbant S, Danacı M. Comparison of the Therapeutic Efficacy of 4Methylpyrazole and N-Acetylcysteine on Acetaminophen (Paracetamol) Hepatotoxicity in Rats. Current Medical Research and Opinion. 2002; 18(2): 78-81.
- Pacifici GM, Allegaert K. Clinical Pharmacology of Paracetamol in Neonates: A Review. Current Therapeutic Research. 2015; 77: 24-30.
- Tripathi D, Trilochana Y. Combined Hepatoprotective Effect of Leaves and Flowers of Bassia latifolia Roxb in Paracetamol Hepatotoxic Rats. Indian Journal of Research in Pharmacy and Biotechnology (IJRPB). 2019; 7(4). https://doi.org/10.31426/ijrpb. 2019.7.4.7411.
- Udom GJ, Yemitan OK, Umoh EE, Mbagwu HO, Ukpe EE, Thomas PS. Hepatoprotective Properties of Ethanol Seed Extract of Citrus paradisi Macfad (Grape Fruit) Against Paracetamol-Induced Hepatotoxicity in Wistar Rats. Journal of Herbal Drugs (An International Journal on Medicinal Herbs) 8(4), 219-225.
- Fadda L, Ali HM, Aldrees GA, Alquraishi NM. Nano ubiquinone: Promising candidate for treatment of renal toxicity induced by over dose of paracetamol. Toxicology reports, 2019; 6, 712-717.
- El-Maddawy ZK, El-Sayed YS. Comparative analysis of the protective effects of curcumin and N-acetyl cysteine against paracetamol-induced hepatic, renal, and testicular toxicity in Wistar rats. Environmental Science and Pollution Research, 2018; 25(4), 3468-3479.
- Battal D. Postmortem rat serum ve dokularında parasetamol dağılımı ve stabilitesinin araştırılması, Doktora Tezi, Çukurova Üniversitesi, Sağlık Bilimleri Enstitüsü, Adli Tıp ABD, Adana, 2009.
- Kolgazi M. Asetaminofen ile oluşturulan karaciğer hasarı patojenezinde nitrik oksit sentaz (nos) ve siklooksijenaz (cox) sistemlerinin rolünün araştırılması, Doktora Tezi, Marmara Üniversitesi, Sağlık Bilimleri Enstitüsü, Fizyoloji Anabilim Dalı, İstanbul, 2013.
- Majeed SK, Ramadhan MA, Monther W. Long-term toxicological effects of paracetamol in rats, Iraqi Journal of Veterinary Sciences. 2013; 27 (1): 65-70.
- Yılmaz I, Cetın A, Bılgıc Y. Hepatoprotective effects of apricot against acetaminophen induced acute hepatotoxicity in rats. Am J Pharma Sci. 2015; 3.2: 44-48. DOI:10.12691/ajps-3-2-3
- Ibrahim IR. Effect of Paracetamol and caffeine in structure and function of thyroidgland in male rats. Journal of College of Education for Pure Science. 2011; 1(5), 89-102.
- Ashour O.M., Sawan A.S. Celecoxib toxicity on rat’s thyroid gland, El-Mınıa Med. Bul. 2009; Vol. 20, No. 1.
- Abeer S.M., Fayroz E.I.N. Effect of chlorpyrifos on thyroid gland of adult male albino rats, Egypt. J. Histol. 2010; Vol. 33, No. 3: 441 – 450.
- Gedikli S. Kronik stresin adrenal bez ve tiroid bezi üzerine etkilerinin morfometrik ve histokimyasal yöntemlerle sıçan modeli üzerinde araştırılması, Yüksek Lisans Tezi, Atatürk Üniversitesi, Sağlık Bilimleri Enstitüsü, Erzurum, 2010.
- Karabulut-bulan Ö., Koyutürk M., Bolkent Ş., Yanardağ R., Tabakoğlu-oğuz A., Sıçan tiroid bezinde kadmiyum hasarına karşı c vitamini, e vitamini ve selenyumun kombine kullanımının etkileri, Cerrahpaşa Tıp Dergisi.2004; 35 (4).
- Manal A.H., Marwa S. Lycopene reduces deltamethrin effects induced thyroid toxicity and DNA damage in albino rats, The Journal of Basic & Applied Zoology. 2013; 66; 155–163.
- Gerard AC, Xhenseval V, Colin IM, Many MC, Denef JF. Evidence for coordinated changes between vascular endothelial growth factor and nitric oxide synthase III immunoreactivity, the functional status of the thyroid follicles, and the microvascular bed during chronic by low iodine and propylthiouracyl in old mice. Eur J Endocrinol. 2000; 142: 651660
- Silva JE. Thyroid hormone control of thermogenesis and energy balance. Thyroid 1995;5:481–492.
- Danforth E Jr, Burger A. The role of thyroid hormones in the control of energy expenditure. Clin Endocrinol Metab 1984;13:581–595.
- Riis ALD, Gravholt CH, Djurhuus CB, Nørrelund H, Jørgensen JOL, Weeke J et al. Elevated regional lipolysis in hyperthyroidism. J Clin Endocrinol Metab. 2002;87:4747–4753.
- Muller MJ, Seitz HJ. Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism. Klin Wochenschr 1984;62:49–55.
- Riis ALD, Jørgensen JOL, Ivarsen P, Frystyk J, Weeke J, & Møller, N. Increased protein turnover and proteolysis is an early and primary feature of shortterm experimental hyperthyroidism in healthy women. J Clin Endocrinol Metab 2008;93:3999–4005.
- Muller MJ, Seitz HJ. Thyroid hormone action on intermediary metabolism. Part III. Protein metabolism in hyper- and hypothyroidism. Klin Wochenschr 1984;62:97–102.
- Peterson, M. E., C. A. Castellano, and Mark Rishniw. "Evaluation of body weight, body condition, and muscle condition in cats with hyperthyroidism." Journal of veterinary internal medicine 30.6 (2016): 1780-1789.
Adverse effects of high-dose paracetamol on thyroid gland of female rats
Year 2020,
, 311 - 319, 03.12.2020
Banu Eren
,
Sare Ulubay
,
Dilek Sağır
,
Burcu Demirel Yılmaz
,
Sevcan Mercan
Abstract
Aim: The aim of this study is to determine whether paracetamol, an analgesic whose mechanism of action is not yet fully known but used unconsciously, causes toxicity on the thyroid gland.
Materials and Methods: A total of 25 female Wistar albino rats divided into five groups as Control (C), Paracetamol 7 days (P7), Paracetamol 14 days (P14), Paracetamol 21 days (P21) and Paracetamol 28 days (P28). The Paracetamol groups were given 750 mg/kg/day paracetamol via oral gavage administration until the day they were sacrificed. Routine histological procedures were applied to the removed thyroid glands. Thyroid tissue sections were evaluated morphometrically and histopathologically.
Results: Cytoplasmic vacuolization and deterioration in follicle and colloid structures were detected in follicular epithelial cells in thyroid tissue sections of groups given paracetamol. The mean of follicle diameter measurement of the P7 group was significantly decreased compared to the control group (p<0.05). In all paracetamol groups, the mean follicular epithelium height increased significantly compared to the control group (p<0.05).
Conclusion: These results show that high doses of paracetamol cause toxic effects on the thyroid gland depending on the duration of use.
Project Number
PYO.FEN.1904.15.001
References
- Ajith TA, Hema U, Aswathy MS. Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status, Food Chem Toxicol. 2007; 45(11):2267-72.
- Emet M, Yayla M. Asetaminofen (Parasetamol) Zehirlenmesi. Turkiye Klinikleri J Emerg Med-Special Topics. 2016; 2.1: 51-7.
- Küçükardalı ,Cinan, U, Acar HV, Özkan S, Top C, Nalbant S, Danacı M. Comparison of the Therapeutic Efficacy of 4Methylpyrazole and N-Acetylcysteine on Acetaminophen (Paracetamol) Hepatotoxicity in Rats. Current Medical Research and Opinion. 2002; 18(2): 78-81.
- Pacifici GM, Allegaert K. Clinical Pharmacology of Paracetamol in Neonates: A Review. Current Therapeutic Research. 2015; 77: 24-30.
- Tripathi D, Trilochana Y. Combined Hepatoprotective Effect of Leaves and Flowers of Bassia latifolia Roxb in Paracetamol Hepatotoxic Rats. Indian Journal of Research in Pharmacy and Biotechnology (IJRPB). 2019; 7(4). https://doi.org/10.31426/ijrpb. 2019.7.4.7411.
- Udom GJ, Yemitan OK, Umoh EE, Mbagwu HO, Ukpe EE, Thomas PS. Hepatoprotective Properties of Ethanol Seed Extract of Citrus paradisi Macfad (Grape Fruit) Against Paracetamol-Induced Hepatotoxicity in Wistar Rats. Journal of Herbal Drugs (An International Journal on Medicinal Herbs) 8(4), 219-225.
- Fadda L, Ali HM, Aldrees GA, Alquraishi NM. Nano ubiquinone: Promising candidate for treatment of renal toxicity induced by over dose of paracetamol. Toxicology reports, 2019; 6, 712-717.
- El-Maddawy ZK, El-Sayed YS. Comparative analysis of the protective effects of curcumin and N-acetyl cysteine against paracetamol-induced hepatic, renal, and testicular toxicity in Wistar rats. Environmental Science and Pollution Research, 2018; 25(4), 3468-3479.
- Battal D. Postmortem rat serum ve dokularında parasetamol dağılımı ve stabilitesinin araştırılması, Doktora Tezi, Çukurova Üniversitesi, Sağlık Bilimleri Enstitüsü, Adli Tıp ABD, Adana, 2009.
- Kolgazi M. Asetaminofen ile oluşturulan karaciğer hasarı patojenezinde nitrik oksit sentaz (nos) ve siklooksijenaz (cox) sistemlerinin rolünün araştırılması, Doktora Tezi, Marmara Üniversitesi, Sağlık Bilimleri Enstitüsü, Fizyoloji Anabilim Dalı, İstanbul, 2013.
- Majeed SK, Ramadhan MA, Monther W. Long-term toxicological effects of paracetamol in rats, Iraqi Journal of Veterinary Sciences. 2013; 27 (1): 65-70.
- Yılmaz I, Cetın A, Bılgıc Y. Hepatoprotective effects of apricot against acetaminophen induced acute hepatotoxicity in rats. Am J Pharma Sci. 2015; 3.2: 44-48. DOI:10.12691/ajps-3-2-3
- Ibrahim IR. Effect of Paracetamol and caffeine in structure and function of thyroidgland in male rats. Journal of College of Education for Pure Science. 2011; 1(5), 89-102.
- Ashour O.M., Sawan A.S. Celecoxib toxicity on rat’s thyroid gland, El-Mınıa Med. Bul. 2009; Vol. 20, No. 1.
- Abeer S.M., Fayroz E.I.N. Effect of chlorpyrifos on thyroid gland of adult male albino rats, Egypt. J. Histol. 2010; Vol. 33, No. 3: 441 – 450.
- Gedikli S. Kronik stresin adrenal bez ve tiroid bezi üzerine etkilerinin morfometrik ve histokimyasal yöntemlerle sıçan modeli üzerinde araştırılması, Yüksek Lisans Tezi, Atatürk Üniversitesi, Sağlık Bilimleri Enstitüsü, Erzurum, 2010.
- Karabulut-bulan Ö., Koyutürk M., Bolkent Ş., Yanardağ R., Tabakoğlu-oğuz A., Sıçan tiroid bezinde kadmiyum hasarına karşı c vitamini, e vitamini ve selenyumun kombine kullanımının etkileri, Cerrahpaşa Tıp Dergisi.2004; 35 (4).
- Manal A.H., Marwa S. Lycopene reduces deltamethrin effects induced thyroid toxicity and DNA damage in albino rats, The Journal of Basic & Applied Zoology. 2013; 66; 155–163.
- Gerard AC, Xhenseval V, Colin IM, Many MC, Denef JF. Evidence for coordinated changes between vascular endothelial growth factor and nitric oxide synthase III immunoreactivity, the functional status of the thyroid follicles, and the microvascular bed during chronic by low iodine and propylthiouracyl in old mice. Eur J Endocrinol. 2000; 142: 651660
- Silva JE. Thyroid hormone control of thermogenesis and energy balance. Thyroid 1995;5:481–492.
- Danforth E Jr, Burger A. The role of thyroid hormones in the control of energy expenditure. Clin Endocrinol Metab 1984;13:581–595.
- Riis ALD, Gravholt CH, Djurhuus CB, Nørrelund H, Jørgensen JOL, Weeke J et al. Elevated regional lipolysis in hyperthyroidism. J Clin Endocrinol Metab. 2002;87:4747–4753.
- Muller MJ, Seitz HJ. Thyroid hormone action on intermediary metabolism. Part II: Lipid metabolism in hypo- and hyperthyroidism. Klin Wochenschr 1984;62:49–55.
- Riis ALD, Jørgensen JOL, Ivarsen P, Frystyk J, Weeke J, & Møller, N. Increased protein turnover and proteolysis is an early and primary feature of shortterm experimental hyperthyroidism in healthy women. J Clin Endocrinol Metab 2008;93:3999–4005.
- Muller MJ, Seitz HJ. Thyroid hormone action on intermediary metabolism. Part III. Protein metabolism in hyper- and hypothyroidism. Klin Wochenschr 1984;62:97–102.
- Peterson, M. E., C. A. Castellano, and Mark Rishniw. "Evaluation of body weight, body condition, and muscle condition in cats with hyperthyroidism." Journal of veterinary internal medicine 30.6 (2016): 1780-1789.