Freitag Abel Felipe, Cardia Gabriel Fernando Esteves, da Rocha Bruno Ambrósio, Aguiar Rafael Pazzinatto, Silva-Comar Francielli Maria de Souza, Spironello Ricardo Alexandre, Grespan Renata, Caparroz-Assef Silvana Martins, Bersani-Amado Ciomar Aparecida, Cuman Roberto Kenji Nakamura
Department of Pharmacology and Therapeutics, State University of Maringá, Avenida Colombo 5790, 870020-900 Maringa, PR, Brazil.
Evid Based Complement Alternat Med. 2015;2015:538317. doi: 10.1155/2015/538317. Epub 2015 Mar 2.
This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3 g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, γ-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, γ-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals.
本研究旨在探讨水飞蓟素(SLM)对自发性高血压大鼠(SHR)的高血压状态以及对乙酰氨基酚(APAP)诱导的肝功能变化的影响。正常血压(N)或高血压(SHR)动物分别接受或未接受APAP(3 g/kg,口服)治疗,或预先接受水飞蓟素治疗。在给予APAP 12小时后,测定所有组的肝功能标志物血浆水平:丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、葡萄糖(GLU)、γ-谷氨酰转移酶(γ-GT)和碱性磷酸酶(ALP)。通过组织学研究评估肝损伤。然后使用其肝脏样本测定髓过氧化物酶(MPO)活性和一氧化氮(NO)生成量,并进行切片用于组织学分析。在SHR组和正常血压大鼠组之间,未观察到ALT、γ-GT和GLU水平存在差异。然而,高血压动物的AST和ALP水平升高。APAP治疗使SHR组和N组的ALT和AST均升高。然而,仅SHR组的γ-GT水平升高。通过MPO活性和NO生成量评估的炎症反应表明,SHR组因白细胞浸润增加而对APAP的作用更敏感。水飞蓟素治疗(利加隆)恢复了APAP在正常血压和高血压动物中诱导的肝细胞功能和组织病理学改变。