Protective Mechanism of Urtica Dioica on Carbon Tetrachloride-Induced Hepatic Encephalopathy in Rats

Öz

Around the world, species from the genus Urtica are commonly used because of their peripheral and central medicinal effects; this is prepared as teas. In recent years, it has become increasingly important to study the beneficial properties of derivatives of Urtica dioica (UD).  The aim of the present study was to evaluate the effects of UD against carbon tetrachloride (CCl₄) induced hepatic encephalopathy (HE). Forty-nine adult (2-months-old) male Sprague dawley rats were used in this study. The models were established by CCl₄  (1 mL/kg body weight; twice a week) given intraperitoneally for 8 weeks. The animals were euthanized by decapitation and rat brains were removed to assess histopathologic changes. Biochemical parameters were assessed in serum samples from the CCl₄-treated rats. UD extracts provided significant protection against CCl₄-induced brain damage by increasing the preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transferase (GGT) and ammonia relative to the control group. Histopathological and immunohistopathological changes of the brain tissue was observed using Hematoxylin-eosin (H&E) staining and c-Fos expression method. In the present study, the protective effect of UD on CCl₄ toxicity was demonstrated through studies of biochemistry and immunohistopathology. Administration of UD may have potential protective effects against CCl₄-induced brain toxicity.

Anahtar Kelimeler

• CCl4,Hepatic encephalopathy (HE),Rat,Urtica dioica

Urtica dioica'nın Sıçanlarda Karbon Tetraklorür ile İndüklenen Hepatik Ensefalopati Üzerine Koruyucu Mekanizması

Öz

Dünya çapında, Urtica cinsinden türler periferik ve merkezi tıbbi etkileri nedeniyle yaygın olarak kullanılmaktadır; bunlar çay olarak hazırlanır. Son yıllarda, Urtica dioica (UD) türevlerinin yararlı özelliklerini incelemek gittikçe önem kazanmıştır. Bu çalışmanın amacı, UD'nin karbon tetraklorür (CCl4) ile indüklenen hepatik ensefalopatiye (HE) karşı etkilerini değerlendirmektir. Bu çalışmada kırk dokuz yetişkin (2 aylık) erkek Sprague dawley sıçanı kullanıldı. Modeller 8 hafta boyunca intraperitoneal olarak verilen CCI₄ (1 mL / kg vücut ağırlığı; haftada iki kez) ile oluşturuldu. Hayvanlar başları kesilerek ötanazi edildi ve sıçan beyinleri histopatolojik değişiklikleri değerlendirmek için çıkarıldı. Biyokimyasal parametreler CCI₄ ile tedavi edilen sıçanlardan alınan serum örneklerinde değerlendirildi. UD ekstraktları, kontrol grubuna göre aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), glutamil transferaz (GGT) ve amonyak seviyeleri gibi biyokimyasal serum parametrelerindeki önleyici değişiklikleri arttırarak CCI₄'ün neden olduğu beyin hasarına karşı önemli bir koruma sağlamıştır. Hematoksilin-eozin (H & E) boyama ve c-fos ekspresyon metodu kullanılarak beyin dokusunun histopatolojik ve immünohistolojik değişiklikleri gözlendi. Bu çalışmada, UD'nin CCI₄ toksisitesi üzerindeki koruyucu etkisi, biyokimya ve immünohistoloji çalışmaları ile gösterilmiştir. UD'nin uygulanması CCI₄'ün neden olduğu beyin toksisitesine karşı potansiyel koruyucu etkilere sahip olabilir.

Anahtar Kelimeler

• Hepatik ensefalopati (HE),CCI4,Sıçan,Urtica dioica

Kaynakça

1. Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK (2009). Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 136, 2159–2168. Ak A, Caliskan O and Cırak C (2006). Economical importance of stinging netle (Urtica spp.) and its cultivation. Journal of Faculty of Agriculture OMU 21, 357–363. Basu S., (2003). Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 189, 113–127. Bémeur C, Butterworth RF (2013). Liver-brain proinflammatory signalling in acute liver failure: role in the pathogenesis of hepatic encephalopathy and brain edema. Metab Brain Dis 28, 145–150. Bhondave PD., Devarshi PP., Mahadik KR., Harsulkar AM (2014). Ashvagandharishta” prepared using yeast consortium from Woodfordia fruticosa flowers exhibit hepatoprotective effect on CCl4 induced liver damage in Wistar rats. J Ethnopharmacol 151 (1), 183–190 Bisht S, Bhandari S, Bisht SN (2012). Urtica dioica L., an undervalued, economically distribution, and elimination of carbon tetrachloride in rat tissues following inhalation and ingestion exposures. Toxicol. Appl. Pharmacol. 143, 120–129. Cichoż-lach H, Michalak A (2013). Current pathogenetic aspects of hepatic encephalopathy and noncirrhotic hyperammonemic encephalopathy. World J Gastroenterol 19, 26–34. Drotman R, Lawhan G (1978). Serum enzymes are indications of chemical induced liver damage Drug Chem Toxicol 1, 163-171. Ferenci P, Pappas SC, Munson PJ (1984). Changes in glutamate receptors on synaptic membranes associated with hepatic encephalopathy or hyperammonemia in the rabbit. Hepatology 4, 24-29. Franklin KB., Paxinos G (2012). The mouse brain in stereotaxic coordinates (fourth ed.), Elsevier, Amsterdam Ghanbari S, Yonessi M, Mohammadirad A, Gholami M, Baeeri M, Khorram-Khorshid HR, et al. (2012). Effects of IMOD™ and Angipars™ on mouse D-galactose-induced model of aging. Daru 20(1), 68. Inaba H, Tsukagoshi A, Kida S (2015). PARP-1 activity is required for the reconsolidation and extinction of contextual fear memory Mol. Brain., 8, 63. important plant. Agric Sci Res J 2, 250–252. Kanter M, Coskun O and Budancamanak M (2005). Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World Journal of Gastroenterology 11(42), 6684–6688. Kaplan PW, Rossetti AO. EEG(2011). patterns and imaging correlations in encephalopathy: encephalopathy part II. J Clin Neurophysiol 28, 233–51. Lahighi SH, Amini K, Moradi P, Asaadi K (2011). Investigating the chemical composition of different parts extracts of bipod nettle Urtica dioica L. İn Tonekabon region. Physiolog 2, 339–342. Losowsky MS, Scott BB (1973). Hepatic encephalopathy. Br Med J 3, 279–281. Mamiya N, Fukushima H, Suzuki A, Matsuyama Z, Homma S, Frankland PW, Kida S (2009). Brain region-specific gene expression activation required for reconsolidation and extinction of contextual fear memory J. Neurosci 29, 402–413 Matsuda KI, Uchiyama K, Mori H, Maejima S, Yamaguchi S, Tanaka M, Tsukahara S (2017). Sexual behavior-associated c-Fos induction in the sagittalis nucleus of the hypothalamus in male rat. Neuroscience Letters 661, 104–107. Mohraz M, Khairandish P, Kazerooni PA, Davarpanah MA, Shahhosseiny MH, Mahdavian B, et al. (2009). A clinical trial on the efficacy of IMOD in AIDS patients. Daru 17(4), 277-284. Otterbein LE, Hedblom A, Harris C, Csizmadia E, Gallo D, Wegiel B (2011). Heme oxygenase-1 and carbon monoxide modulate DNA repair through ataxia-telangiectasia mutated (ATM) protein Proc Natl Acad. Sci. U. S. A., 108, 14491–14496. Roche E, Buteau J, Aniento I, Reig JA, Soria B, Prentki M (1999). Palmitate and oleate induce the immediate-early response genes c-fos and nur-77 in the pancreatic beta-cell line INS-1. Diabetes 48, 2007-2014. Sanzgiri UY, Srivatsan V, Muralidhara S, Dallas CE, Bruckner JV (1997). Uptake, distribution, and elimination of carbon tetrachloride in rat tissues following inhalation and ingestion exposures. Toxicol Appl Pharmacol 143(1), 120-129. Sikander M, Malik S, Parveen K, Ahmad M, Yadav D, Hafeez ZB, Bansal M (2013). Hepatoprotective effect of Origanum vulgare in Wistar rats against carbon tetrachloride-induced hepatotoxicity. Protoplasma 250, 483–493. Tirkey N, Pilkhawl S, Kuhad A, Chopra K (2005). Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharmacol 5, 1–8. Vaquero J, Chung C, Cahill ME, Blei AT (2003). Pathogenesis of hepatic encephalopathy in acute liver failure. Semin Liver Dis 23, 259–269 Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P (2014). Hepatic encephalopathy in chronic liver disease: Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 60, 715–735 Vilstrup H, Amodio P, Bajaj J, et al. (2014b). Hepatic encephalopathy in chronic liver disease: Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 60(2), 715–735. Webster LT, Gabuzda GJ (1957). Ammonium uptake by the extremities and brain in hepatic coma. J Clin Investig 50, 414–424. Yanagida N, Sato S, Asaumi T, Nagakura K, Ogura K, Ebisawa M (2016). Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children. Int Arch Allergy Immunol 171(3-4), 265-268. Yanagida S, Motomura K, Ohashi A, Hiraoka K, Miura T, Kanba S (2016). Effect of acute imipramine administration on the pattern of forced swim- induced c-Fos expression in the Mouse brain Neuroscience Lett 629, 119–124. Yang X, Yang S, Guo Y, Jiao Y, Zhao Y (2013). Compositional characterisation of soluble apple polysaccharides, and their antioxidant and hepatoprotective effects on acute CCl4 caused liver damage in mice. Food Chem 138, 1256–1264.