Osuntokun Opeyemi Samson, Olayiwola Gbola, Atere Tope Gafar, Adedokun Kabiru Isola, Oladokun Olayemi Olutobi
Department of Physiology, Faculty of Basic Medical Sciences, Osun State University Osogbo, Nigeria.
Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
Toxicol Rep. 2020 Nov 24;7:1592-1596. doi: 10.1016/j.toxrep.2020.11.006. eCollection 2020.
This study investigated the effects of co-administration of carbamazepine (CBZ) with grape () seed methanolic extract (GSME) on liver toxicity.
Thirty-five male rats (145-155 g) were randomized into 5 groups (n = 7) and administered with propylene glycol (PG 0.1 mL/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) orally for 28 days. Twenty-four hours after the last dose, changes in the body weights were determined. The rats were euthanized by cervical dislocation. The liver was weighed and later homogenized; while the supernatant was analyzed biochemically. The liver tissues were preserved in 10 % neutral-buffered formalin for the histomorphological investigation.
There was significant (p = 0.0001) decrease in the body weight following carbamazepine treatment. The relative liver weight also decreased significantly (p = 0.0004) across the treatment group compared with control. The activities of the liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutathione activities), including the concentrations of malondialdehyde, increased significantly (p ≤ 0.0004) following carbamazepine treatment. Various morphological alterations were observed, especially in the photomicrograph of the CBZ treated rats. However, these derangements were attenuated significantly in the CBZ - GSME co-treated group.
This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.
本研究调查了卡马西平(CBZ)与葡萄籽甲醇提取物(GSME)联合给药对肝脏毒性的影响。
将35只雄性大鼠(145 - 155克)随机分为5组(每组n = 7),分别给予丙二醇(PG 0.1毫升/天)、CBZ(25毫克/千克)、CBZ(25毫克/千克) + GSME(200毫克/千克)、CBZ(25毫克/千克) + GSME(100毫克/千克)或CBZ(25毫克/千克) + GSME(50毫克/千克),口服给药28天。末次给药24小时后,测定体重变化。通过颈椎脱臼法对大鼠实施安乐死。称取肝脏重量,随后进行匀浆;同时对上清液进行生化分析。将肝脏组织保存在10%中性缓冲福尔马林中进行组织形态学研究。
卡马西平治疗后体重显著下降(p = 0.0001)。与对照组相比,各治疗组的相对肝脏重量也显著下降(p = 0.0004)。卡马西平治疗后,肝脏酶(天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶和谷胱甘肽活性)的活性以及丙二醛浓度均显著升高(p ≤ 0.0004)。观察到各种形态学改变,尤其是在CBZ治疗大鼠的显微照片中。然而,在CBZ - GSME联合治疗组中,这些紊乱显著减轻。
本研究得出结论,GSME治疗可能作为卡马西平诱导的肝毒性/功能障碍的一种潜在治疗药物。