Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misurata University, Misurata, Libya.
Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
Biomed Pharmacother. 2018 Aug;104:366-374. doi: 10.1016/j.biopha.2018.05.049. Epub 2018 May 25.
The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group. These PCM-induced effects were associated with oxidative stress as demonstrated by increased levels of malondialdehyde (MDA) and reduced levels of hepatic antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Pretreatment of PLME decreased ALT and AST by 78.2% and tissue MDA by 54.1%, and increased hepatic GPx (3.5 folds), CAT (7 folds) and SOD (2.5 folds) compared to PCM group. These PLME-mediated effects were comparable to NAC pretreatment. Histological analysis demonstrates that PLME conserved hepatic tissues against lesions such as inflammation, centrilobular necrosis, and hemorrhages induced by PCM. In contrast, PLAE-mediated effects were less effective in reducing levels of liver function enzymes, oxidative stress, and liver histopathological profiles, and restoring antioxidant defenses against PCM-induced intoxication. These findings indicate that PLME exerts protective effects against PCM-induced hepatotoxicity via scavenging free radicals and restoring hepatic antioxidant enzymes. Thus, PLME and its bioactive components could further be evaluated for their pharmacological properties against drug-induced deleterious effects.
本研究旨在探讨以水提和醇提的形式从海枣叶中提取的抗氧化剂（简称 PLAE 和 PLME）对广泛应用的止痛药扑热息痛（PCM）诱导的肝毒性的影响。实验将大鼠分为 PCM 处理组（1500mg/kg）、PLAE 和 PLME 处理组（300mg/kg）以及 N-乙酰半胱氨酸（NAC，50mg/kg）处理组，通过测定肝功能、氧化应激、抗氧化防御系统和肝毒性，评估各组大鼠的状态。我们发现，与对照组（未处理组）相比，PCM 可显著提高血清肝标志物天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、γ-谷氨酰转肽酶（GGT）和胆红素的水平。这些 PCM 诱导的影响与氧化应激有关，表现为丙二醛（MDA）水平升高和肝抗氧化酶谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）水平降低。与 PCM 组相比，PLME 预处理可使 ALT 和 AST 分别降低 78.2%和 54.1%，使组织 MDA 降低 54.1%，使肝 GPx（3.5 倍）、CAT（7 倍）和 SOD（2.5 倍）升高。这些 PLME 介导的作用与 NAC 预处理相当。组织学分析表明，PLME 可保护肝组织免受 PCM 诱导的炎症、中央坏死和出血等病变的影响。相比之下，PLAE 对降低肝功能酶、氧化应激和肝组织病理谱水平以及恢复对 PCM 诱导的中毒的抗氧化防御作用的影响较小。这些结果表明，PLME 通过清除自由基和恢复肝抗氧化酶来发挥对 PCM 诱导的肝毒性的保护作用。因此，PLME 及其生物活性成分可进一步评估其对药物诱导的有害作用的药理学特性。
