青蒿琥酯和黄酮类化合物对扑热息痛和四氯化碳诱导的原代小鼠肝细胞细胞毒性的肝保护特性比较评估。
Comparative assessment of hepatoprotective properties of Artesunate and flavonoids from on acetaminophen and carbon tetrachloride-induced cytotoxicity in primary mice hepatocytes.
作者信息
Djeungoue Petga Marie Ange, Kouam Arnaud Fondjo, Chougouo Kengne Rosine Désirée, Galani Tietcheu Boris Rosnay, Louokdom Josué Simo, Ngantchouko Ngalemo Claude Bérenger, Chuisseu Djamen Pascal Dieudonné, Moundipa Paul Fewou
机构信息
Higher Institute of Health Sciences, Université des Montagnes, P.O. Box 208, Bangangté, Cameroon.
Medical Research and Applied Biochemistry Laboratory, Department of Biomedical Sciences, Faculty of Health Sciences, University of Buea, PO Box 63, Buea, Cameroon.
出版信息
Metabol Open. 2023 Apr 6;18:100241. doi: 10.1016/j.metop.2023.100241. eCollection 2023 Jun.
BACKGROUND
Artesunate (ART) is a semi-synthetized molecule from Artemisinin, an active compound isolated from the medicinal plant , widely used for the treatment of malaria. Previous studies reported that ART may exert a dual effect on the liver. Accordingly, this study investigated the potential protective action of ART against Acetaminophen (APAP) and Carbon tetrachloride (CCl)-induced hepatotoxicity in primary mice hepatocytes, in comparison to that of flavonoid extracted from (FAA). In addition, the antioxidant properties of FAA were also assessed.
METHODS
The antioxidant activities of FAA and Ascorbic acid (ASC) (0.01-100 μg/mL) were assessed through inhibition of lipid peroxidation, reduction of ferric and phosphomolydenum, and hydroxyl and DPPH radicals scavenging assays. The hepatoprotective effects of FAA and ART (0.1-100 μg/mL) were evaluated against APAP (11 mM) or CCl4 (4 mM) induced oxidative damage in primary mouse hepatocytes. Biochemical parameters associated with hepatotoxicity assessed include cell viability, cell membrane integrity, cellular glutathione, and antioxidant enzyme activities.
RESULTS
The obtained finding revealed FAA displayed a remarkable antioxidant activities as evidenced by the low IC/EC values (3.85-19.32 μg/mL), comparable to that of ASC (3.26-18.04 μg/mL). When tested at 10 μg/mL, both FAA and ART significantly (p˂0.05) preserved cell viability, inhibited alanine aminotransferase leakage and lipid membrane peroxidation, and restored superoxide dismutase and catalase activities and glutathione content induced by APAP or CCl in a similar way as Silymarin. However, ART showed a significant (p˂0.05) cytotoxic effect on hepatocytes at 100 and 1000 μg/mL and did not confer obvious protection at 100 μg/mL.
CONCLUSION
Overall, our data demonstrated that ART harms mice hepatocytes at high concentration while conferring relative protection against APAP and CCl-hepatotoxicity at low concentration. In contrast, FAA effectively protects liver cells without cytotoxicity effect, event at 100 μg/mL. Accordingly, ART should be given to the patient only under a medical prescription.
背景
青蒿琥酯（ART）是一种从青蒿素半合成的分子，青蒿素是从药用植物中分离出的一种活性化合物，广泛用于治疗疟疾。先前的研究报道，ART可能对肝脏产生双重作用。因此，本研究调查了ART与从[植物名称未给出]中提取的类黄酮（FAA）相比，对原代小鼠肝细胞中对乙酰氨基酚（APAP）和四氯化碳（CCl）诱导的肝毒性的潜在保护作用。此外，还评估了FAA的抗氧化特性。
方法
通过抑制脂质过氧化、还原铁和磷钼以及清除羟基和DPPH自由基试验，评估FAA和抗坏血酸（ASC）（0.01 - 100μg/mL）的抗氧化活性。评估FAA和ART（0.1 - 100μg/mL）对原代小鼠肝细胞中APAP（11mM）或CCl4（4mM）诱导的氧化损伤的肝保护作用。评估的与肝毒性相关的生化参数包括细胞活力、细胞膜完整性、细胞内谷胱甘肽和抗氧化酶活性。
结果
获得的结果表明，FAA显示出显著的抗氧化活性，低IC/EC值（3.85 - 19.32μg/mL）证明了这一点，与ASC（3.26 - 18.04μg/mL）相当。当以10μg/mL进行测试时，FAA和ART均显著（p˂0.05）保持细胞活力，抑制丙氨酸转氨酶泄漏和脂质膜过氧化，并以与水飞蓟宾类似的方式恢复由APAP或CCl诱导的超氧化物歧化酶和过氧化氢酶活性以及谷胱甘肽含量。然而，ART在100和1000μg/mL时对肝细胞显示出显著（p˂0.05）的细胞毒性作用，并且在100μg/mL时未提供明显的保护作用。
结论
总体而言，我们的数据表明，ART在高浓度时会损害小鼠肝细胞，而在低浓度时对APAP和CCl诱导的肝毒性具有相对保护作用。相比之下，FAA即使在100μg/mL时也能有效保护肝细胞而无细胞毒性作用。因此，ART应仅在医生处方下给予患者。
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