Effect of Short-Term Inhalation of The Herbicide 2,4D on Cardiac Remodeling: Morphological Aspects

Abstract Background: Brazil is the worldwide leader in the long-term use of pesticides and herbicides. This compromises the health of handlers by causing harmful neurological, respiratory, and cardiovascular changes. The herbicide 2.4D has been shown to cause cardiac overload with subsequent pathological remodeling. Objective: To analyze the cardiac morphological repercussions on the left ventricle (LV) of mice submitted to nebulization by the herbicide 2.4D. Methods: Fifteen mice were divided into three groups: control group (CG; n = 5) exposed to nebulization with sodium chloride solution; low concentration group (LCG; n = 5) exposed to nebulization of the herbicide 2.4D with 3.71 x 10-3 grams; and high concentration group (HCG; n = 5) exposed to nebulization of the herbicide 2.4D with 9.28 x 10-3 grams for 15 minutes. The fractal dimension analysis was performed through the box-counting method. Later, the ImageJ program was used to calculate the fractal dimension of each group. To evaluate cardiac remodeling, histological slides were prepared and stained with Hematoxylin-Eosin (HE). Fifty areas of cardiomyocytes were analyzed per animal. The comparisons between groups were performed by ANOVA One-Way with Tukey’s posttest (p < 0.05). Results: There was no change in fractal dimension values between the CG = 1.37 ± 0.02, LCG = 1.33 ± 0.04 and the HCG = 1.33 ± 0.07 groups. However, cardiac hypertrophy occurred in the HCG = 303.9 ± 38.80 µm(2) when compared to the CG group = 236.9 ± 61.71 µm(2) (p = 0.034). Conclusion: The herbicide 2.4D used for 72 hours did not promote cardiotoxicity when evaluated by fractal dimension. However, cardiomyocyte hypertrophy was observed in the LV.

【摘要】
背景：巴西是全球长期使用农药与除草剂最多的国家，此举会损害施药人员的健康，引发神经、呼吸及心血管系统的病理性损害。已有研究表明，除草剂2,4-D（2.4D）可引发心脏负荷过载，并伴随后续的病理重塑。
目的：分析经2,4-D除草剂雾化暴露的小鼠左心室（LV）的心脏形态学影响。
方法：将15只小鼠分为3组：对照组（CG；n=5），予以氯化钠溶液雾化暴露；低浓度组（LCG；n=5），予以3.71×10⁻³克剂量的2,4-D除草剂雾化暴露；高浓度组（HCG；n=5），予以9.28×10⁻³克剂量的2,4-D除草剂雾化暴露，每次暴露时长15分钟。采用盒计数法开展分形维数分析，随后使用ImageJ软件计算各组的分形维数值。为评估心脏重塑情况，制备苏木精-伊红（HE）染色的组织切片，每只动物分析50个心肌细胞区域。组间比较采用单因素方差分析（One-Way ANOVA）结合Tukey事后检验，检验水准设定为p<0.05。
结果：对照组（CG=1.37±0.02）、低浓度组（LCG=1.33±0.04）与高浓度组（HCG=1.33±0.07）的分形维数值无显著差异。但与对照组（236.9±61.71 µm²）相比，高浓度组小鼠出现心肌肥大（303.9±38.80 µm²，p=0.034）。
结论：经72小时暴露的2,4-D除草剂，通过分形维数评估未表现出心脏毒性，但可观察到左心室心肌细胞肥大。