Iuliu Hatieganu University of Medicine and Pharmacy, Department of Physiology, Cluj-Napoca, Romania.
J Physiol Pharmacol. 2020 Feb;71(1). doi: 10.26402/jpp.2020.1.04. Epub 2020 Apr 27.
Inflammation and oxidative stress are interrelated processes, during which many pathological processes lead to the reactive oxygen species (ROS) and the cytokines release. The aim of this experimental study was to analyse the effects of chlorogenic acid, in oral daily administration, against the oxidative stress and oedema development in experimental carrageenan-induced rat paw inflammation. The oxidative stress parameters were investigated after a paw inflammation was produced in rats that previoulsy received, for 14 days, either chlorogenic acid (100 mg/day or 150 mg/day) or indomethacin (1 mg/kg/day). The paw oedema was measured through plethysmometry made at 2, 6 and 24 hours after carrageenan injection. The oxidative stress was investigated through spectrophotometry. Blood samples, paw skin and kidneys were collected to investigate malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG). The protein expression of oxidative stress-related pathways was analysed in skin and kidneys through Western blot. The present study showed that indomethacin and both doses of chlorogenic acid, after 14 days of oral administration, exerted antioedematous effects during the inflammation development after carrageenan local injection. Compared to the group that received only carrageenan injection, significant decreases of the inflamed paw volume were shown in the treated groups (P < 0.001), in all inflammation phases. The lipid peroxidation was significantly decreased by both doses of chlorogenic acid in inflamed skin (P < 0.0001) and kidney (P < 0.0001). In serum, it was significantly inhibited by indomethacin (P < 0.01) and by 100 mg/day of chlorogenic acid (P < 0.05). The antioxidant protection, evaluated through the ratio GSH/GSSG, was significantly increased by chlorogenic acid in inflamed skin (P < 0.0001) and kidney (100 mg/day, P < 0.01; 150 mg/day, P < 0.0001). In serum, only indomethacin administration produced significant increases of the antioxidant protection (P < 0.05). Western blot analysis showed significant decreases of COX-2 in inflamed skin and kidney in the groups of rats that received indomethacin or 100 mg/day of chlorogenic acid. The effects of chlorogenic acid on NF-κB and pNF-κB were dose-dependent.
炎症和氧化应激是相互关联的过程,在此过程中,许多病理过程导致活性氧(ROS)和细胞因子的释放。本实验研究的目的是分析氯原酸(每日口服)对实验性角叉菜胶诱导的大鼠足肿胀炎症中氧化应激和水肿发展的影响。在先前接受氯原酸(100 mg/天或 150 mg/天)或吲哚美辛(1 mg/kg/天)14 天的大鼠产生足炎后,通过分光光度法研究了氧化应激参数。通过在角叉菜胶注射后 2、6 和 24 小时进行体积描记术测量足肿胀。通过分光光度法研究氧化应激。收集血液样本、足皮和肾脏,以研究丙二醛(MDA)、谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)。通过 Western blot 分析皮肤和肾脏中与氧化应激相关途径的蛋白质表达。本研究表明,在局部注射角叉菜胶后,14 天口服给予吲哚美辛和两种剂量的氯原酸均能在炎症发展过程中发挥抗水肿作用。与仅接受角叉菜胶注射的组相比,所有炎症阶段中,治疗组(P <0.001)炎症足体积明显减少。两种剂量的氯原酸均显著降低了炎症皮肤(P <0.0001)和肾脏(P <0.0001)中的脂质过氧化。血清中,吲哚美辛(P <0.01)和 100 mg/天的氯原酸(P <0.05)显著抑制了脂质过氧化。通过氯原酸评估的谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)比值的抗氧化保护作用在炎症皮肤(P <0.0001)和肾脏(100 mg/天,P <0.01;150 mg/天,P <0.0001)中均显著增加。血清中,只有吲哚美辛给药才能显著增加抗氧化保护作用(P <0.05)。Western blot 分析显示,在接受吲哚美辛或 100 mg/天氯原酸的大鼠组中,COX-2 在炎症皮肤和肾脏中的表达均显著降低。氯原酸对 NF-κB 和 pNF-κB 的作用呈剂量依赖性。