Algefare Abdulmohsen I, Alfwuaires Manal, Famurewa Ademola C, Elsawy Hany, Sedky Azza
Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria.
Toxicol Rep. 2024 Jan 13;12:128-134. doi: 10.1016/j.toxrep.2024.01.007. eCollection 2024 Jun.
Carbon tetrachloride (CCl) is a classic chemical hepatotoxicant that triggers liver damage through hepatic exacerbation of oxidative stress. Geraniol (GRL) is a natural bioactive acyclic monoterpene with several pharmacological effects. We thus explored whether GRL could prevent CCl-triggered hepatic toxicity. Rats were divided and administered GRL (100 mg/kg) and/or CCl (1 ml/kg of 1:1 v/v CCl: olive oil) in Control group, GRL group, CCl group, GRL + CCl groups 2 times per week for 4 consecutive weeks. CCl caused significantly (p < 0.05) elevated serum activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TB), whereas the albumin (ALB) and total protein (TP) levels were significantly (p < 0.05) reduced relative to the control group. The liver activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) decreased significantly (p < 0.05), while malondialdehyde (MDA) level evidently elevated in comparison to the control group. The CCl exposure caused significant increases in proinflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), apoptotic caspase-3 and caspase-9 levels, whereas the anti-inflammatory interleukin-4 (IL-4) and interleukin-10 (IL-10) were reduced in consistent with histopathological changes compared to the control. On the contrary, the GRL administration prevented the hepatic toxicity and lesions through restoration of liver status markers, antioxidant enzyme activities, MDA, cytokines and apoptosis in comparison to the CCl group. Altogether, the findings reveal that GRL could abrogate CCl-provoked hepatic toxicity via inhibition of hepatic oxidative stress, inflammation and apoptosis in rats.
四氯化碳（CCl₄）是一种典型的化学性肝毒物，可通过加剧肝脏氧化应激来引发肝损伤。香叶醇（GRL）是一种具有多种药理作用的天然生物活性无环单萜。因此，我们探究了香叶醇是否能预防四氯化碳引发的肝毒性。将大鼠分为对照组、香叶醇组、四氯化碳组、香叶醇 + 四氯化碳组，每周给药2次，连续4周，分别给予香叶醇（100 mg/kg）和/或四氯化碳（1 ml/kg，四氯化碳与橄榄油体积比为1:1）。四氯化碳导致血清碱性磷酸酶（ALP）、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和总胆红素（TB）活性显著升高（p < 0.05），而白蛋白（ALB）和总蛋白（TP）水平相对于对照组显著降低（p < 0.05）。与对照组相比，肝脏过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性显著降低（p < 0.05），而丙二醛（MDA）水平明显升高。四氯化碳暴露导致促炎细胞因子白细胞介素 -6（IL -6）和肿瘤坏死因子 -α（TNF -α）、凋亡相关的半胱天冬酶 -3和半胱天冬酶 -9水平显著升高，而抗炎细胞因子白细胞介素 -4（IL -4）和白细胞介素 -10（IL -10）与对照组相比呈一致性降低，同时伴有组织病理学变化。相反，与四氯化碳组相比，给予香叶醇可通过恢复肝脏状态标志物、抗氧化酶活性、丙二醛、细胞因子和细胞凋亡情况来预防肝毒性和肝损伤。总之，研究结果表明香叶醇可通过抑制大鼠肝脏氧化应激、炎症和细胞凋亡来消除四氯化碳引发的肝毒性。
