PDF(Pubmed)
Abstract：
UNASSIGNED: Hyperammonemia and hepatotoxicity are well-known complications of valproic acid (VPA) poisoning. The objective of this study is to evaluate the potential role of carnitine in mitigating the adverse effects of acute VPA toxicity in mice.
UNASSIGNED: 54 male mice (25-30 g) were randomly assigned to one of three categories, including acute, sub-acute, and chronic poisoning. Each category contained 3 groups, each consisting of 6 mice (Group 1: control, Group 2: VPA treated, and Group 3: VPA + carnitine treated). The animals were sacrificed 24 hours after the initial injection, and their blood, liver, and brain samples were compared between groups of each category regarding liver function biomarkers, oxidative stress markers, ammonia level, and liver histopathologic changes using one-way ANOVA followed by Tukey\'s multiple comparison test.
UNASSIGNED: The administration of VPA increased the serum level of aspartate aminotransferase (AST) (p=0.003) and alanine aminotransferase (ALT) (p=0.001), as well as serum, and brain level of ammonia (p=0.0001 for both) in the intervention group. Elevated levels of lipid peroxidation and oxidative stress (p=0.0001 for both) in the liver tissue, decreased liver glutathione (p=0.0001) and ferric ion-reducing antioxidant power (FRAP) (p=0.0001), and histopathologic changes in the form of moderate to severe inflammation were observed. Administration of VPA + carnitine reduced AST (p=0.05) and ALT (p=0.01), increased the FRAP, reduced free oxygen radicals and liver lipid peroxidation (p=0.0001 for all), and decreased tissue damage in the form of moderate inflammation. The administration of carnitine was ineffective in reducing brain or plasma ammonia levels in acute VPA-treated animals (p = 0.0115).
UNASSIGNED: Although the administration of carnitine has been suggested as a protective remedy in cases of VPA toxicity, according to the present study, it did not have an antidotal effect and did not prevent encephalopathy or liver injury in acute VPA toxicity.
UNASSIGNED: 54 male mice (25-30 g) were randomly assigned to one of three categories, including acute, sub-acute, and chronic poisoning. Each category contained 3 groups, each consisting of 6 mice (Group 1: control, Group 2: VPA treated, and Group 3: VPA + carnitine treated). The animals were sacrificed 24 hours after the initial injection, and their blood, liver, and brain samples were compared between groups of each category regarding liver function biomarkers, oxidative stress markers, ammonia level, and liver histopathologic changes using one-way ANOVA followed by Tukey\'s multiple comparison test.
UNASSIGNED: The administration of VPA increased the serum level of aspartate aminotransferase (AST) (p=0.003) and alanine aminotransferase (ALT) (p=0.001), as well as serum, and brain level of ammonia (p=0.0001 for both) in the intervention group. Elevated levels of lipid peroxidation and oxidative stress (p=0.0001 for both) in the liver tissue, decreased liver glutathione (p=0.0001) and ferric ion-reducing antioxidant power (FRAP) (p=0.0001), and histopathologic changes in the form of moderate to severe inflammation were observed. Administration of VPA + carnitine reduced AST (p=0.05) and ALT (p=0.01), increased the FRAP, reduced free oxygen radicals and liver lipid peroxidation (p=0.0001 for all), and decreased tissue damage in the form of moderate inflammation. The administration of carnitine was ineffective in reducing brain or plasma ammonia levels in acute VPA-treated animals (p = 0.0115).
UNASSIGNED: Although the administration of carnitine has been suggested as a protective remedy in cases of VPA toxicity, according to the present study, it did not have an antidotal effect and did not prevent encephalopathy or liver injury in acute VPA toxicity.
摘要：
■高氨血症和肝毒性是丙戊酸（VPA）中毒的众所周知的并发症。这项研究的目的是评估肉碱在减轻小鼠急性VPA毒性不良反应中的潜在作用。
■将54只雄性小鼠（25-30克）随机分为三类之一，包括急性,亚急性,慢性中毒。每个类别包含3组，每组由6只小鼠组成(第1组：对照，第2组：VPA治疗，和第3组：VPA+肉碱治疗）。在初次注射后24小时处死动物，和他们的血,肝脏,和脑样本在每个类别的组之间进行了关于肝功能生物标志物的比较，氧化应激标志物，氨水平，使用单向方差分析和肝脏组织病理学变化，然后进行Tukey的多重比较检验。
■服用VPA会增加血清天冬氨酸转氨酶（AST）（p=0.003）和丙氨酸转氨酶（ALT）（p=0.001），以及血清，干预组的脑氨水平(两者p=0.0001)。肝脏组织中脂质过氧化和氧化应激水平升高（两者p=0.0001），降低肝脏谷胱甘肽（p=0.0001）和铁离子还原抗氧化能力（FRAP）（p=0.0001），观察到中度至重度炎症形式的组织病理学变化。施用VPA+肉碱降低AST（p=0.05）和ALT（p=0.01），增加了FRAP,减少氧自由基和肝脏脂质过氧化（p=0.0001所有），以中度炎症的形式减少组织损伤。在急性VPA治疗的动物中，肉碱的给药对降低脑或血浆氨水平无效（p=0.0115）。
■尽管在VPA毒性的情况下，肉碱的给药被认为是一种保护性的补救措施，根据目前的研究，它没有解毒作用,也不能预防急性VPA毒性的脑病或肝损伤.
■将54只雄性小鼠（25-30克）随机分为三类之一，包括急性,亚急性,慢性中毒。每个类别包含3组，每组由6只小鼠组成(第1组：对照，第2组：VPA治疗，和第3组：VPA+肉碱治疗）。在初次注射后24小时处死动物，和他们的血,肝脏,和脑样本在每个类别的组之间进行了关于肝功能生物标志物的比较，氧化应激标志物，氨水平，使用单向方差分析和肝脏组织病理学变化，然后进行Tukey的多重比较检验。
■服用VPA会增加血清天冬氨酸转氨酶（AST）（p=0.003）和丙氨酸转氨酶（ALT）（p=0.001），以及血清，干预组的脑氨水平(两者p=0.0001)。肝脏组织中脂质过氧化和氧化应激水平升高（两者p=0.0001），降低肝脏谷胱甘肽（p=0.0001）和铁离子还原抗氧化能力（FRAP）（p=0.0001），观察到中度至重度炎症形式的组织病理学变化。施用VPA+肉碱降低AST（p=0.05）和ALT（p=0.01），增加了FRAP,减少氧自由基和肝脏脂质过氧化（p=0.0001所有），以中度炎症的形式减少组织损伤。在急性VPA治疗的动物中，肉碱的给药对降低脑或血浆氨水平无效（p=0.0115）。
■尽管在VPA毒性的情况下，肉碱的给药被认为是一种保护性的补救措施，根据目前的研究，它没有解毒作用,也不能预防急性VPA毒性的脑病或肝损伤.
