Luo Miaosha, Dong Lei, Li Jing, Wang Yan, Shang Boxin
Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):8990-6. eCollection 2015.
Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with the effects of antioxidation, anti-inflammation and anti-fibrosis that has been shown to induce damage in liver. The purpose of this study is to investigate the effects and possible mechanisms of PTX on thioacetamide (TAA)-induced acute liver injury in rats. Male Sprague-Dawley (SD) rats were divided into four groups: control, PTX, TAA and PTX+TAA treated groups. Rats were administrated TAA together with or without PTX for a week and sacrificed 24 h after the last intragastric administration of PTX. Histopathological analysis was carried out. The liver function, the indices of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in liver tissues, and pro-inflammatory cytokines expressions were examined. The mRNA level of NF-κB p65 in liver was also determined. PTX significantly attenuated TAA-induced liver injury. The serum transaminase and MDA levels were reduced while the levels of SOD and GSH were increased, as compared with the TAA-treated group. PTX also remarkably suppressed the secretions of pro-inflammatory cytokines and the nuclear factor-κB (NF-κB) activation induced by TAA. In addition, the histopathological analysis showed that the range and degree of liver tissue lesions were improved obviously in PTX treated group. Pentoxifylline could ameliorate the effects of thioacetamide-induced acute liver injury in rats by inhibiting oxidative stress, expressions of pro-inflammatory cytokines and NF-κB activation.
己酮可可碱(PTX)是一种非选择性磷酸二酯酶抑制剂,具有抗氧化、抗炎和抗纤维化作用,已被证明可导致肝脏损伤。本研究旨在探讨PTX对硫代乙酰胺(TAA)诱导的大鼠急性肝损伤的影响及可能机制。雄性Sprague-Dawley(SD)大鼠分为四组:对照组、PTX组、TAA组和PTX+TAA处理组。大鼠给予TAA,同时或不给予PTX,持续一周,并在最后一次灌胃给予PTX后24小时处死。进行组织病理学分析。检测肝功能、肝组织中氧化应激指标包括丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)以及促炎细胞因子表达。还测定肝脏中NF-κB p65的mRNA水平。PTX显著减轻了TAA诱导的肝损伤。与TAA处理组相比,血清转氨酶和MDA水平降低,而SOD和GSH水平升高。PTX还显著抑制了促炎细胞因子的分泌以及TAA诱导的核因子-κB(NF-κB)激活。此外,组织病理学分析表明,PTX处理组肝组织病变的范围和程度明显改善。己酮可可碱可通过抑制氧化应激、促炎细胞因子表达和NF-κB激活来改善硫代乙酰胺诱导的大鼠急性肝损伤的影响。