Department of Veterinary Physiology and Biochemistry, University of Ibadan, Nigeria.
Department of Anatomy, University of Ibadan, Nigeria.
Niger J Physiol Sci. 2022 Jun 30;37(1):35-42. doi: 10.54548/njps.v37i1.5.
This study was designed to investigate the modulatory role of Luteolin (Lut), a flavonoid phytochemical, on haemodynamic parameters and the potential mechanisms involving renal Angiotensin II (AT2R) and Mineralocorticoid (MCR) receptors in renal toxicity induced by co-exposure to Diclofenac (Dcf) and sodium fluoride (NaF) in rats.Male Wistar rats were administered with either vehicle (control), Dcf only (9 mg/kg orally) or concurrently with NaF (300 ppm in drinking water). Other groups were treated with LutA (100 mg/kg) or LutB (200 mg/kg) along with Dcf and NaF exposures. All treatments lasted 8 days, following which blood pressure indices were measured using tail-cuff plethysmography. Renal expressions of AT2R and MCR were studied with immunohistochemistry, while biomarkers of oxidative and antioxidant status were also measured in the kidneys. Systolic, diastolic and mean arterial pressures were significantly (p<0.05) reduced in Dcf-treated rats, compared to control values. However, co-treatment with NaF or Lut restored these parameters. While the expression of AT2R and MCR was high in the Dcf and Dcf+NaF groups, treatment with Lut caused obvious reduction in the renal expression of these receptors. Increased lipid peroxidation (Malondialdehyde) and protein oxidation (protein carbonyls) with a lowering of reduced glutathione levels contributed to the renal toxicity of Dcf, and these were significantly ameliorated in Lut-treated rats. In conclusion, the preservation of haemodynamic indices by Lutin the experimental ratsprobably included mechanisms involving down-regulation of renal expressions of AT2R and MCR, reduction of oxidative stress and an improvement of renal antioxidant status.
本研究旨在探讨木樨草素（Lut）作为一种黄酮类植物化学物质对双氯芬酸（Dcf）和氟化钠（NaF）共同暴露诱导的大鼠肾毒性中血流动力学参数的调节作用，以及涉及肾血管紧张素 II（AT2R）和盐皮质激素受体（MCR）的潜在机制。雄性 Wistar 大鼠给予载体（对照）、仅 Dcf（口服 9mg/kg）或同时给予 NaF（饮用水中 300ppm）。其他组用 LutA（100mg/kg）或 LutB（200mg/kg）与 Dcf 和 NaF 暴露一起治疗。所有治疗持续 8 天，之后使用尾套体积描记法测量血压指数。用免疫组织化学研究 AT2R 和 MCR 的肾表达，同时还测量了肾脏氧化和抗氧化状态的生物标志物。与对照组相比，Dcf 处理的大鼠收缩压、舒张压和平均动脉压显著（p<0.05）降低。然而，NaF 或 Lut 的共同治疗恢复了这些参数。Dcf 和 Dcf+NaF 组中 AT2R 和 MCR 的表达较高，而 Lut 治疗导致这些受体在肾脏中的表达明显降低。脂质过氧化（丙二醛）和蛋白质氧化（蛋白质羰基）增加，还原型谷胱甘肽水平降低，导致 Dcf 的肾毒性，而 Lut 治疗的大鼠明显改善了这些毒性。总之，Lut 在实验大鼠中维持血流动力学指数，可能包括下调肾 AT2R 和 MCR 的表达、减轻氧化应激和改善肾抗氧化状态的机制。
