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柚皮素对铅诱导的大鼠氧化应激、炎症和细胞凋亡的肝脏保护和神经保护作用

Hepatoprotective and Neuroprotective Effects of Naringenin against Lead-Induced Oxidative Stress, Inflammation, and Apoptosis in Rats.

作者信息

Mansour Lubna A H, Elshopakey Gehad E, Abdelhamid Fatma M, Albukhari Talat A, Almehmadi Samah J, Refaat Bassem, El-Boshy Mohamed, Risha Engy F

机构信息

Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.

Department of Immunology and Hematology, Faculty of Medicine, Umm Al-Qura University, Makkah P.O. Box 6165, Saudi Arabia.

出版信息

Biomedicines. 2023 Apr 3;11(4):1080. doi: 10.3390/biomedicines11041080.

Abstract

Naringenin (NRG) is one of the most important naturally occurring flavonoids, predominantly found in some edible fruits, such as citrus species and tomatoes. It has several biological activities, such as antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. The heavy metal lead is toxic and triggers oxidative stress, which causes toxicity in many organs, including the liver and brain. This study explored the potential protective role of NRG in hepato- and neurotoxicity caused by lead acetate in rats. Four groups of ten male albino rats were included: group 1 was a control, group 2 was orally treated with lead acetate (LA) at a dose of 500 mg/kg BW, group 3 was treated with naringenin (NRG) at a dose of 50 mg/kg BW, and group 4 was treated with 500 mg/kg LA and 50 mg/kg NRG for 4 weeks. Then, blood was taken, the rats were euthanized, and liver and brain tissues were collected. The findings revealed that LA exposure induced hepatotoxicity with a significant increase in liver function markers ( < 0.05). In addition, albumin and total protein (TP) and the albumin/globulin ratio (A/G ratio) ( < 0.05) were markedly lowered, whereas the serum globulin level ( > 0.05) was unaltered. LA also induced oxidative damage, demonstrated by a significant increase in malonaldehyde (MDA) ( < 0.05), together with a pronounced antioxidant system reduction (SOD, CAT, and GSH) ( < 0.05) in both liver and brain tissues. Inflammation of the liver and brain caused by LA was indicated by increased levels of nuclear factor kappa beta (NF-κβ) and caspase-3, ( < 0.05), and the levels of B-cell lymphocyte-2 (BCL-2) and interleukin-10 (IL-10) ( < 0.05) were decreased. Brain tissue damage induced by LA toxicity was demonstrated by the downregulation of the neurotransmitters norepinephrine (NE), dopamine (DA), serotonin (5-HT), and creatine kinase (CK-BB) ( < 0.05). Additionally, the liver and brain of LA-treated rats displayed notable histopathological damage. In conclusion, NRG has potential hepato- and neuroprotective effects against lead acetate toxicity. However, additional research is needed in order to propose naringenin as a potential protective agent against renal and cardiac toxicity mediated by lead acetate.

摘要

柚皮素(NRG)是最重要的天然黄酮类化合物之一,主要存在于一些可食用水果中,如柑橘类水果和番茄。它具有多种生物活性,如抗氧化、抗肿瘤、抗病毒、抗菌、抗炎、抗脂肪生成和心脏保护作用。重金属铅具有毒性,会引发氧化应激,导致包括肝脏和大脑在内的许多器官中毒。本研究探讨了NRG对醋酸铅所致大鼠肝毒性和神经毒性的潜在保护作用。实验纳入四组,每组十只雄性白化大鼠:第一组为对照组,第二组口服500 mg/kg体重的醋酸铅(LA),第三组给予50 mg/kg体重的柚皮素(NRG),第四组给予500 mg/kg LA和50 mg/kg NRG,持续4周。然后采集血液,对大鼠实施安乐死,并收集肝脏和脑组织。研究结果显示,接触LA会诱发肝毒性,肝功能指标显著升高(P<0.05)。此外,白蛋白、总蛋白(TP)以及白蛋白/球蛋白比值(A/G比值)显著降低(P<0.05),而血清球蛋白水平未发生改变(P>0.05)。LA还会引发氧化损伤,表现为丙二醛(MDA)显著增加(P<0.05),同时肝脏和脑组织中的抗氧化系统(超氧化物歧化酶、过氧化氢酶和谷胱甘肽)明显降低(P<0.05)。LA所致的肝脏和脑部炎症表现为核因子κB(NF-κβ)和半胱天冬酶-3水平升高(P<0.05),B细胞淋巴瘤-2(BCL-2)和白细胞介素-10(IL-10)水平降低(P<0.05)。LA毒性所致的脑组织损伤表现为神经递质去甲肾上腺素(NE)、多巴胺(DA)、血清素(5-HT)和肌酸激酶(CK-BB)下调(P<0.05)。此外,LA处理组大鼠的肝脏和脑部出现明显的组织病理学损伤。总之,NRG对醋酸铅毒性具有潜在的肝脏和神经保护作用。然而,为了将柚皮素推荐为对抗醋酸铅介导的肾脏和心脏毒性的潜在保护剂,还需要进行更多研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaec/10135523/19c7b0563365/biomedicines-11-01080-g001.jpg

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