Hamdaoui Latifa, El Feki Hafedh, Ben Amor Marwa, Oudadesse Hassane, Badraoui Riadh, Khalil Naila, Brahmi Faten, Jilani Saoussen, Aloufi Bandar, Ben Amara Ibtissem, Rebai Tarek
Laboratory of Induced Diseases and Development, Sfax Faculty of Medicine, University of Sfax, Sfax 3029, Tunisia.
Faculty of Sciences of Sfax, University of Sfax, Sfax 3029, Tunisia.
Toxics. 2025 May 29;13(6):456. doi: 10.3390/toxics13060456.
Glyphosate (N-phosphonomethylglycine) is a widely used organophosphorus herbicide that inhibits the shikimate pathway, a crucial metabolic route responsible for the synthesis of aromatic amino acids in plants and certain microorganisms. Due to its broad-spectrum activity, glyphosate serves as the main active ingredient in various commercial herbicide formulations, including Roundup and Kalach 360 SL (KL). It poses a health hazard to animals and humans due to its persistence in soil, water erosion, and crops. The aim of our study was to continue the previous research to explore the impact of KL on bone using physico-chemical parameters and in silico studies after exposing female rats for 60 days. The in silico study concerned the assessment of binding affinity and molecular interactions using computational modeling approach. The rats were allocated into three experimental groups: group 1 ( = 6) served as controls, while groups 2 and 3 received low and high doses (Dose 1: 126 mg/Kg and Dose 2: 315 mg/Kg) of KL dissolved in water, respectively. All rats were sacrificed after 60 days of exposure. XRD and FTIR spectrum analysis of bone tissues in female rats showed significant histoarchitectural changes associated with bone mineralization disruption. Our results have demonstrated that sub-chronic exposure of adult female rats to KL causes bone rarefaction, as confirmed by a previous histological study. This physico-chemical study has further confirmed the harmful impact of KL on the crystalline fraction of bone tissue, composed of hydroxyapatite crystals. In addition, the computational analyses showed that glyphosate binds to 3 Glu form of osteocalcin (3 Glu-OCN) (4MZZ) and decarboxylated osteocalcin (8I75) with good affinities and strong molecular interactions, which justified and supported the in vivo findings. In conclusion, KL may interfere with hydroxyapatite and osteocalcin and, therefore, impair bone remodeling and metabolism.
草甘膦（N-膦酰基甲基甘氨酸）是一种广泛使用的有机磷除草剂，它抑制莽草酸途径，这是植物和某些微生物中负责合成芳香族氨基酸的关键代谢途径。由于其广谱活性，草甘膦是各种商业除草剂配方（包括农达和卡乐施360 SL（KL））中的主要活性成分。由于其在土壤、水土流失和作物中的持久性，它对动物和人类构成健康危害。我们研究的目的是延续之前的研究，在雌性大鼠暴露60天后，使用物理化学参数和计算机模拟研究来探索KL对骨骼的影响。计算机模拟研究涉及使用计算建模方法评估结合亲和力和分子相互作用。将大鼠分为三个实验组：第1组（n = 6）作为对照组，而第2组和第3组分别接受溶解在水中的低剂量和高剂量（剂量1：126 mg/Kg和剂量2：315 mg/Kg）的KL。暴露60天后处死所有大鼠。雌性大鼠骨组织的XRD和FTIR光谱分析显示与骨矿化破坏相关的显著组织架构变化。我们的结果表明，成年雌性大鼠亚慢性暴露于KL会导致骨质稀疏，这与之前的组织学研究一致。这项物理化学研究进一步证实了KL对由羟基磷灰石晶体组成的骨组织结晶部分的有害影响。此外，计算分析表明草甘膦与骨钙素的3种Glu形式（3 Glu-OCN）（4MZZ）和脱羧骨钙素（8I75）具有良好的亲和力和强烈的分子相互作用，这证明并支持了体内研究结果。总之，KL可能会干扰羟基磷灰石和骨钙素，从而损害骨重塑和代谢。
