[Effects of curcumin on neurobehavior and oxidative stress in hippocampus of rats exposed to manganese]

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2021 Nov 20;39(11):801-807. doi: 10.3760/cma.j.cn121094-20201126-00651.
[Article in Chinese]

Abstract

Objective: To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats. Methods: From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl(2)·4H(2)O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl(2)·4H(2)O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results: The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased (P<0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased (P<0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day (P<0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased (P<0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened (P<0.05) , and the average number of crossing the original platform was increased (P<0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups (P<0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased (P<0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese (P<0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group (P<0.05) . Conclusion: Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.

目的: 建立亚慢性锰中毒动物模型,初步探讨锰对大鼠神经行为学和海马组织氧化应激的影响及姜黄素对锰中毒大鼠神经毒性的保护作用。 方法: 于2019年7至12月,将80只SPF级雄性SD大鼠,按体重采用随机数字表法分为8组,分别为空白对照组,低、中、高剂量染锰组,低、中、高剂量姜黄素拮抗组及姜黄素组,每组10只大鼠。低、中、高剂量染锰组分别给予5、10和15 mg/kg四水氯化锰(MnCl(2)·4H(2)O)腹腔注射染毒,低、中、高剂量姜黄素拮抗组给予15 mg/kg MnCl(2)·4H(2)O腹腔注射染毒并经口分别给予100、200和400 mg/kg的姜黄素,姜黄素组经口给予400 mg/kg姜黄素。每周染毒5 d,1次/d,连续染毒16周。染毒结束后对各组大鼠进行神经行为学测试(平衡木试验、水迷宫试验和避暗试验),取大鼠海马组织做病理学检查并检测其氧化应激指标。 结果: 平衡木试验结果显示,与空白对照组比较,中、高剂量染锰组大鼠平衡木评分均增高(P<0.05);与高剂量染锰组比较,低、中、高剂量姜黄素拮抗组平衡木评分均降低(P<0.05)。水迷宫试验结果显示,与空白对照组比较,从第3天开始,中、高剂量染锰毒组逃避潜伏期延长(P<0.05),各剂量染锰组穿环次数均降低(P<0.05);与高剂量染锰组比较,从第3天开始,中、高剂量姜黄素拮抗组逃避潜伏期缩短、穿环次数增加(P<0.05)。避暗试验结果显示,与空白对照组比较,中、高剂量染锰组避暗试验错误次数增多(P<0.05);与高剂量染锰组比较,中、高剂量姜黄素拮抗组避暗试验错误次数降低(P<0.05)。病理学检查可见,染锰组大鼠出现不同程度的神经细胞变性、坏死,细胞结构模糊不清且数量减少,姜黄素拮抗后上述现象改善。氧化应激指标结果显示,与空白对照组比较,中、高剂量染锰组大鼠海马组织超氧化物歧化酶活力降低、丙二醛含量增加(P<0.05);与高剂量染锰组比较,中、高剂量姜黄素拮抗组超氧化物歧化酶活力增高、丙二醛含量减少(P<0.05)。 结论: 亚慢性锰暴露可致大鼠平衡功能、学习记忆能力下降,海马组织神经细胞损伤且处于氧化应激状态;姜黄素能提高锰中毒大鼠的平衡功能和学习记忆能力,改善锰暴露所致大鼠海马组织神经损害,对锰导致的神经毒性具有一定的保护作用。.

Keywords: Curcumin; Manganese poisoning; Neuroethology; Oxidative stress; Rats.

MeSH terms

  • Animals
  • Curcumin* / pharmacology
  • Hippocampus
  • Male
  • Manganese / toxicity
  • Maze Learning
  • Oxidative Stress
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Manganese
  • Curcumin