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评价 对多柔比星诱导的荷瘤小鼠(DLA)毒性的保护作用。

Evaluation of the protective effects of against doxorubicin-induced toxicity in Dalton's Lymphoma Ascites (DLA) bearing mice.

机构信息

Department of Zoology, Mizoram University, Aizawl, Mizoram, India.

Mizoram Science, Technology and Innovation Council, Aizawl, Mizoram, India.

出版信息

Drug Chem Toxicol. 2022 May;45(3):1243-1253. doi: 10.1080/01480545.2020.1812630. Epub 2020 Aug 28.

DOI:10.1080/01480545.2020.1812630
PMID:32854544
Abstract

The toxic side effects of doxorubicin in cancer treatment are well established. Here we show that methanolic extract of the fungus offers protection against cardio- and hepatotoxicity induced by doxorubicin (DOX) in Dalton's Lymphoma Ascites (DLA) bearing mice. Treatment of DLA mice with 20 mg/kg of doxorubicin significantly increased the activities of serum toxicity markers including aspartate amino-transferase (AST), alanine amino-transferase (ALT) and lactate dehydrogenase (LDH). However, co-administration of doxorubicin (20 mg/kg) by intraperitoneal injection and (150 mg/kg) by oral gavage in DLA mice lowered the AST, ALT, and LDH activities when compared to DOX alone treatment. Treatment of DLA mice with DOX alone resulted in reduced GSH contents, and decreased the activities of glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD). Treatment of DOX-administered DLA mice with however increased the GSH content and elevated the activities of GST, CAT, and SOD. Among the various solvent extracts of methanolic extract showed the highest phenolic (376.5 ± 15.24 mg GAE/g) and flavonoid (4717.79 ± 170.22 mg quercetin/g) contents compared to the aqueous (216.3 ± 7.33 mg GAE/g) and chloroform extracts (137.27 ± 1.03 mg GAE/g). Consistently, the methanolic extract was found to possess the highest free radical scavenging activities when compared to the aqueous and chloroform extracts as measured by ABTS and DPPH assays. Our results thus suggest that the protective roles of in DOX-induced toxicity could be an attribute of the antioxidant properties conferred by the high phenolic and flavonoid contents.

摘要

多柔比星在癌症治疗中的毒副作用是众所周知的。在这里,我们表明,真菌的甲醇提取物提供了对多柔比星(DOX)诱导的心脏和肝毒性的保护,在携带道尔顿淋巴瘤腹水(DLA)的小鼠中。用 20mg/kg 的多柔比星处理 DLA 小鼠,显著增加了血清毒性标志物的活性,包括天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和乳酸脱氢酶(LDH)。然而,与单独使用 DOX 相比,在 DLA 小鼠中腹腔注射多柔比星(20mg/kg)并口服(150mg/kg)给药,降低了 AST、ALT 和 LDH 的活性。单独用 DOX 处理 DLA 小鼠导致 GSH 含量降低,降低了谷胱甘肽-S-转移酶(GST)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)的活性。然而,用 治疗 DOX 给药的 DLA 小鼠增加了 GSH 含量,并提高了 GST、CAT 和 SOD 的活性。在 的各种溶剂提取物中,与水(216.3±7.33mgGAE/g)和氯仿提取物(137.27±1.03mgGAE/g)相比,甲醇提取物显示出最高的酚(376.5±15.24mgGAE/g)和类黄酮(4717.79±170.22mg 槲皮素/g)含量。一致地,与水和氯仿提取物相比,甲醇提取物在通过 ABTS 和 DPPH 测定测量的自由基清除活性方面表现出最高的自由基清除活性。因此,我们的结果表明,在 DOX 诱导的毒性中, 的保护作用可能归因于高酚和类黄酮含量赋予的抗氧化特性。

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