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Luteolin mitigates potassium dichromate-induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim-1/Nrf2 signaling pathways
Environmental Toxicology ( IF 4.4 ) Pub Date : 2021-07-16 , DOI: 10.1002/tox.23329
Omolola Victoria Awoyomi 1 , Yemisi Dorcas Adeoye 1 , Ademola Adetokunbo Oyagbemi 2 , Temitayo Olabisi Ajibade 2 , Ebunoluwa Rachael Asenuga 3 , Idayat Titilayo Gbadamosi 4 , Blessing Seun Ogunpolu 5 , Olufunke Olubunmi Falayi 6 , Fasilat Oluwakemi Hassan 2 , Temidayo Olutayo Omobowale 5 , Oluwatosin Adetola Arojojoye 7 , Olufunke Eunice Ola-Davies 2 , Adebowale Benard Saba 6 , Adeolu Alex Adedapo 6 , Oluwafemi Omoniyi Oguntibeju 8 , Momoh Audu Yakubu 9
Affiliation  

Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K2Cr2O7) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K2Cr2O7), Group C (Luteolin 100 mg/kg and K2Cr2O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2Cr2O7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K2Cr2O7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim-1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre-treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim-1, cardiac troponin I and up-regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms.

中文翻译:

木犀草素通过调节 Kim-1/Nrf2 信号通路减轻重铬酸钾诱导的肾毒性、心脏毒性和基因毒性

环境和职业接触铬化合物已成为肾脏疾病的潜在病因,自由基产生过多、细胞凋亡和炎症。重铬酸钾 (K 2 Cr 2 O 7 ) 的这些病理生理机制与肾毒性和心脏毒性密切相关。本研究对 40 只健康大鼠分为四个实验组:A 组(生理盐水)、B 组(30 mg/kg K 2 Cr 2 O 7)、C 组,评估了木犀草素(一种已知的强效抗氧化剂)的心脏保护和肾脏保护作用(木犀草素 100 mg/kg 和 K 2 Cr 2 O 730 mg/kg)和 D 组(木犀草素 200 mg/kg 和 K 2 Cr 2 O 7 30 mg/kg)。测定了抗氧化防御系统、氧化应激、血压和微核多染红细胞 (MnPE)、肾脏免疫组织化学、损伤分子 (Kim-1)、核因子红细胞 2 相关因子 2 (Nrf2) 和心肌肌钙蛋白 I 的标志物。K 2 Cr 2 O 7 的给药收缩压、舒张压和平均动脉血压的血压参数、氧化应激标志物和微核多染红细胞的频率增加,同时降低血清一氧化氮水平。肾Kim-1和心肌肌钙蛋白I表达较高,但免疫组织化学分析记录到肾和心脏Nrf2表达较低。木犀草素预处理可恢复血压参数,同时降低氧化应激指标,增强抗氧化机制和血清一氧化氮水平,降低 Kim-1、心肌肌钙蛋白 I 的表达,并上调心脏和肾脏 Nrf2,降低微核多染红细胞的频率。因此,综上所述,这项研究证明了心脏保护作用,
更新日期:2021-07-16
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