Ommati Mohammad Mehdi, Jamshidzadeh Akram, Saeed Mohsen, Rezaei Mohammad, Heidari Reza
Department of Bioinformatics, College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, China.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Clin Exp Hepatol. 2022 Sep;8(3):178-187. doi: 10.5114/ceh.2022.118299. Epub 2022 Aug 3.
Hepatic encephalopathy (HE) is a serious clinical problem leading to severe neurological disorders and death. No specific treatment is available for the management of HE-associated neurological damage. This study aimed to evaluate the effect of dextromethorphan (DXM) on oxidative stress and disturbed locomotor activity in an animal model of HE.
In the current study, BALB/c mice received acetaminophen (APAP; 1000 mg/kg, intraperitoneally [IP]). Dextromethorphan (0.5, 1, 5, 10 mg/kg, subcutaneously [SC]) was injected in three doses (every 6 h), starting two hours after acetaminophen. Animals' locomotor activity, brain and plasma ammonia levels, as well as biomarkers of oxidative stress and inflammatory cytokines in the brain tissue, were assessed 24 hours after acetaminophen injection.
It was found that APAP administration was significantly associated with liver damage and increased plasma biomarkers of liver injury. Ammonia levels in plasma and brain tissue of APAP-treated mice also increased significantly. There was also a significant difference in motor activity between the control and APAP-treated animals. The acute liver injury also increased the brain level of pro-inflammatory cytokines (tumor necrosis factor a [TNF-a], interleukin 6 [IL-6], and interleukin 1b [IL-1b]). It was found that DXM could significantly improve the motor activity of animals in all doses and decrease the biomarkers of inflammation and oxidative stress in the brain tissue of animals with hyperammonemia.
The effect of dextromethorphan on oxidative stress and inflammation seems to be a major mechanism for its neuroprotective properties in HE. Based on these data DXM could be applied as an effective pharmacological option against HE-associated brain injury.
肝性脑病（HE）是一个严重的临床问题，可导致严重的神经功能障碍甚至死亡。目前尚无针对HE相关神经损伤的特效治疗方法。本研究旨在评估右美沙芬（DXM）对HE动物模型氧化应激和运动活动紊乱的影响。
在本研究中，BALB/c小鼠腹腔注射对乙酰氨基酚（APAP；1000 mg/kg）。右美沙芬（0.5、1、5、10 mg/kg，皮下注射）分三个剂量（每6小时一次）注射，在对乙酰氨基酚注射两小时后开始。在对乙酰氨基酚注射24小时后，评估动物的运动活动、脑和血浆氨水平，以及脑组织中氧化应激生物标志物和炎性细胞因子。
发现给予APAP与肝损伤以及肝脏损伤血浆生物标志物升高显著相关。APAP处理小鼠的血浆和脑组织氨水平也显著升高。对照组和APAP处理动物之间的运动活动也存在显著差异。急性肝损伤还增加了促炎细胞因子（肿瘤坏死因子α [TNF-α]、白细胞介素6 [IL-6]和白细胞介素1β [IL-1β]）的脑水平。发现DXM可显著改善所有剂量动物的运动活动，并降低高氨血症动物脑组织中的炎症和氧化应激生物标志物。
右美沙芬对氧化应激和炎症的作用似乎是其在HE中具有神经保护特性的主要机制。基于这些数据，DXM可作为一种有效的药理学选择用于对抗HE相关脑损伤。
