Pretreatment with Gallic Acid Mitigates Cyclophosphamide Induced Inflammation and Oxidative Stress in Mice.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Saeed Baharmi, Heibatullah Kalantari, Mojtaba Kalantar, Mehdi Goudarzi, Esrafil Mansouri, Hadi Kalantar
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引用次数: 5

Abstract

Background: Cyclophosphamide (CP) as an alkylating compound has been widely applied to treat cancer and autoimmune diseases. CP is observed to be nephrotoxic in humans and animals because it produces reactive oxygen species. Gallic Acid (GA), a polyhydroxy phenolic compound, is reported to exhibit antioxidant and anti-inflammatory effects.

Objective: The current research aimed at evaluating the GA effect on CP-related renal toxicity.

Methods: In total, 35 male mice were assigned to 5 groups. Group1: receiving normal saline, group 2: CP group, receiving one CP injection (200 mg/kg; i.p.) on day 6. Groups 3 and 4: GA+CP, GA (10 and 30 mg/kg; p.o.; respectively) received through six consecutive days plus CP on the 6th day 2 hr after the last dose of GA, group 5: received GA (30 mg/kg; p.o.) for six consecutive days. Then on day 7, blood samples were collected for determining Creatinine (Cr), serum kidney injury molecule-1 (KIM-1), Blood Urea Nitrogen (BUN), and Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations. Malondialdehyde (MDA), Nitric Oxide (NO) concentration, Catalase (CAT), Superoxide Dismutase (SOD), Glutathione (GSH), Glutathione Peroxidase (GPx) activities, and IL-1β, TNF-α levels were assessed in renal tissue.

Results: CP administration significantly increases KIM-1, NGAL, Cr, BUN, MDA, NO, IL-1β, and TNF-α level. It also decreases GSH concentration, SOD, GPx, and CAT function. Pretreatment with GA prevented these changes. Histopathological assessments approved the GA protective effect.

Conclusion: Our results showed that GA is possibly effective as a protective agent in cyclophosphamide- associated toxicities.

没食子酸预处理减轻小鼠环磷酰胺诱导的炎症和氧化应激。
背景:环磷酰胺(Cyclophosphamide, CP)作为一种烷基化化合物已广泛应用于癌症和自身免疫性疾病的治疗。CP被观察到对人类和动物有肾毒性,因为它产生活性氧。没食子酸(GA)是一种多羟基酚类化合物,具有抗氧化和抗炎作用。目的:评价GA对cp相关性肾毒性的影响。方法:雄性小鼠35只,随机分为5组。组1:给予生理盐水;组2:CP组,给予CP注射液1次(200 mg/kg;第6天)。3、4组:GA+CP, GA(10、30 mg/kg);订单。分别于末次给药后第6天2小时连续6天加CP,第5组:给药GA (30 mg/kg;p.o.)连续6天。第7天,取血测定肌酐(Cr)、血清肾损伤分子-1 (KIM-1)、血尿素氮(BUN)、中性粒细胞明胶酶相关脂钙蛋白(NGAL)浓度。测定肾组织丙二醛(MDA)、一氧化氮(NO)浓度、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)活性及IL-1β、TNF-α水平。结果:CP组显著升高KIM-1、NGAL、Cr、BUN、MDA、NO、IL-1β、TNF-α水平。它还能降低GSH浓度、SOD、GPx和CAT功能。GA预处理阻止了这些变化。组织病理学评估证实了GA的保护作用。结论:我们的研究结果表明,GA可能是一种有效的环磷酰胺相关毒性的保护剂。
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来源期刊
Current molecular pharmacology
Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
4.90
自引率
3.70%
发文量
112
期刊介绍: Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.
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