Swamy Ravindra Shantakumar, Kumar Nitesh, Shenoy Smita, Kumar Naveen, Rao Vanishree
Division of Anatomy, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Hajipur, Hajipur, Bihar 844102, India.
Biomed Rep. 2024 Apr 29;20(6):97. doi: 10.3892/br.2024.1785. eCollection 2024 Jun.
There is a lack of treatment for the detrimental effects of fluorosis. Sodium fluoride at a concentration of 10 ppm induces stress, depression and memory impairment in adult Wistar rats. Naringin, a flavanone glycoside isolated from citrus fruits such as lemons and oranges, possesses anti-inflammatory, antioxidant and neuroprotective properties; therefore, it was used for treatment of fluoride induced toxicity in the present study. Adult Wistar rats were divided into eight groups (n=8). The normal control (NOR) group was provided with normal tap water. The sodium fluoride (FLU)10 group received water containing 10 ppm sodium fluoride for 60 days. The treatment groups (FLU10NAR100 and FLU10NAR50) received drinking water with 10 ppm sodium fluoride along with Naringin 100 and 50 mg/kg body weight (bw) per oral gavage, respectively. The NAR100 and NAR50 groups received Naringin 100 and 50 mg/kg bw. The PRONAR100 and PRONAR50 groups received Naringin 100 and 50 mg/kg bw for the first 15 days and then subsequently received FLU10 ppm for 60 days (total of 75 days). All animals were subjected to behavioural tests consisting of the open field test (OFT), forced swim test (FST) and novel object recognition test (NORT). After euthanasia, the hippocampus and prefrontal cortex were stained with Cresyl violet. To measure the oxidative stress caused by fluoride and its effect on antioxidant levels, estimation of reduced glutathione (GSH) by Ellman's method, lipid peroxidation (LPO) measured in terms of the MDA:thiobarbituric acid reaction and catalase was performed. To evaluate the effect of fluoride on activity of acetylcholine, estimation of acetylcholinesterase (AChE) by Ellman's method was performed. In NORT and FST, significant changes (P<0.05) were present in the FLU10NAR100 and FLU10NAR50 groups compared with the FLU10 group, showing recovery from memory deficit and depression. The OFT results were insignificant. The LPO was reduced in all the other groups except the FLU10 group, with statistically significant changes. Catalase activity was significantly lower in FLU10 as compared with the NAR100, NAR50, PRONAR100 and PRONAR50 groups. GSH and AChE activities did not show significant changes as compared with the FLU10 group. The CA3 and prefrontal cortex viable and degenerated neuron count in the FLU10 group were insignificant compared with all other groups, except for the NAR100 and NAR50 groups. Thus, Naringin can be a useful drug to avoid the neurological effects of fluoride.
目前缺乏针对氟中毒有害影响的治疗方法。浓度为10 ppm的氟化钠会导致成年Wistar大鼠出现应激、抑郁和记忆障碍。柚皮苷是一种从柠檬和橙子等柑橘类水果中分离出的黄酮苷,具有抗炎、抗氧化和神经保护特性;因此,在本研究中用其来治疗氟诱导的毒性。成年Wistar大鼠被分为八组(n = 8)。正常对照组(NOR)饮用正常的自来水。氟化钠(FLU)10组饮用含10 ppm氟化钠的水60天。治疗组(FLU10NAR100和FLU10NAR50)分别饮用含10 ppm氟化钠的水,并通过口服灌胃给予每千克体重100和50 mg的柚皮苷。NAR100和NAR50组给予每千克体重100和50 mg的柚皮苷。PRONAR100和PRONAR50组在最初15天给予每千克体重100和50 mg的柚皮苷,随后饮用10 ppm的氟化钠60天(共75天)。所有动物均接受行为测试,包括旷场试验(OFT)、强迫游泳试验(FST)和新物体识别试验(NORT)。安乐死后,用甲酚紫对海马体和前额叶皮质进行染色。为了测量氟引起的氧化应激及其对抗氧化水平的影响,采用Ellman法测定还原型谷胱甘肽(GSH),通过丙二醛:硫代巴比妥酸反应测定脂质过氧化(LPO)并检测过氧化氢酶。为了评估氟对乙酰胆碱活性的影响,采用Ellman法测定乙酰胆碱酯酶(AChE)。在NORT和FST中,与FLU10组相比,FLU10NAR100和FLU10NAR50组出现了显著变化(P<0.05),表明记忆缺陷和抑郁有所恢复。OFT结果无显著差异。除FLU10组外,所有其他组的LPO均降低,且有统计学意义的变化。与NAR100、NAR50、PRONAR100和PRONAR50组相比,FLU10组的过氧化氢酶活性显著降低。与FLU10组相比,GSH和AChE活性未显示出显著变化。与所有其他组相比,除NAR100和NAR50组外,FLU10组CA3和前额叶皮质中存活和退化神经元数量无显著差异。因此,柚皮苷可能是一种避免氟对神经系统产生影响的有效药物。