糖化是归因于衰老和相关发病率的潜在机制之一。没有可用的药物来对抗这种有害现象。本研究旨在探讨间苯三酚(PHL)在临床前水平的抗糖基化潜力。大鼠用甲基乙二醛(MGO,17.25mg/kg,i.p.持续14天),以诱导电刺激应激。治疗组接受额外的测试药物(PHL;0.25mg/kg,0.5mg/kg,和1mg/kg)或标准氨基胍(AG,50mg/kg)或生理盐水(对照,5ml/kg)。在14天内,注意体重和食物摄入量。之后,使用Morris水迷宫(MWM)评估认知功能,同时通过肝功能测试评估肝肾功能(胆红素,碱性磷酸酶,SGPT,和SGOT)和肌酐,使用化学分析仪。使用ELISA技术定量血液中的羧甲基赖氨酸(CML)水平。对大脑进行了组织病理学研究,肝脏,和肾脏使用H&E染色。此外,qPCR用于定量TNF-α的表达,愤怒和BACE-1(大脑),愤怒,TNF-α,乙二醛酶-I(肝脏)和愤怒,TNF-α,和VEGF(肾),而甘油醛-3-磷酸脱氢酶(GAPDH)用作参考管家基因。有关体重和食物摄入量的数据没有显示出明显的变化。在MWM中,MGO治疗导致达到目标象限的时间显著增加,同时减少了在目标象限中花费的时间和通过平台位置的交叉次数。所有这些作用均被AG和PHL抑制。导航地图还显示了空间记忆的保留。此外,MGO诱导的肝肾功能指标改变通过AG和PHL治疗得到改善.发现MGO治疗后血浆CML水平升高,而AG和PHL的伴随给药抵制了这种增加。组织病理学评估显示肝肾和脑组织无特异性病理。qPCR数据显示所有基因的表达增强,尤其是TNF-α和BACE,发现在AG和PHL处理后均减少。PHL阻止了大脑,肝,MGO诱导的糖基化应激引起的肾脏损害。因此,PHL,一种临床上使用的抗痉挛药物,作为抗糖化药物的潜在候选药物。
Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore
phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug.