Glufosinate (ammonium salt) is a key herbicide to manage weeds, which is formulated as a racemic mixture of d, l-phosphinothricin [1]. Glufosinate inhibits glutamine synthetase (GS), leading to the accumulation of ammonia and metabolites from the photorespiration pathway (such as acetic acid and malonic acid), as well as the consumption of other intermediates (such as glycine, serine, hydroxypropionic acid, and glyeraldehyde), and causes a significant accumulation of reactive oxygen species (ROS), resulting in the rapid death of plant cells[2]. Glufosinate has been widely used to inhibit the formation of glutamine and to regulate the seed components of soybean varieties[3].
In vitro, Glufosinate treatment (0.5µg/ml) for 72 hours significantly increased the frequencies of chromosome aberration and micronucleus in human lymphocytes [4]. Treatment with 100µM Glufosinate for 12 days increased the expression of neurogenic protein 2 in mouse neural stem cells (NSCs) and altered the glial differentiation of NSCs [5]. Treatment with 10µg/ml Glufosinate for 24 hours induced apoptosis of mouse embryonic neuroepithelial cells, characterized by fragmentation of DNA and condensation and separation of chromatin[6]. Treatment with 10µg/ml Glufosinate for 1 hour inhibited the mitochondrial function of human sperm cells, by decreasing the oxygen consumption rate in the active and in the passive state of mitochondrial respiration [7].
In vivo, Glufosinate treatment via oral administration at a dose of 20mg/kg (twice a day) for 14 days reduced the levels of GS in the tumors of Lewis lung carcinoma (LLC) cell-xenograft mouse models, decreased the lung metastases, and induced the aggregation of cytotoxic T lymphocytes and the normalization of tumor blood vessels[8].
References:
[1] Takano H K, Dayan F E. Glufosinate‐ammonium: a review of the current state of knowledge[J]. Pest Management Science, 2020, 76(12): 3911-3925.
[2] Takano H K, Beffa R, Preston C, et al. A novel insight into the mode of action of glufosinate: how reactive oxygen species are formed[J]. Photosynthesis Research, 2020, 144(3): 361-372.
[3] Reddy K N, Zablotowicz R M, Bellaloui N, et al. Glufosinate Effects on Nitrogen Nutrition, Growth, Yield, and Seed Composition in Glufosinate‐Resistant and Glufosinate‐Sensitive Soybean[J]. International Journal of Agronomy, 2011, 2011(1): 109280.
[4] Santovito A, Ruberto S, Gendusa C, et al. In vitro evaluation of genomic damage induced by glyphosate on human lymphocytes[J]. Environmental Science and Pollution Research, 2018, 25(34): 34693-34700.
[5] Feat-Vetel J, Larrigaldie V, Meyer-Dilhet G, et al. Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice[J]. Neurotoxicology, 2018, 69: 152-163.
[6] Watanabe T. Apoptosis induced by glufosinate ammonium in the neuroepithelium of developing mouse embryos in culture[J]. Neuroscience letters, 1997, 222(1): 17-20.
[7] Ferramosca A, Lorenzetti S, Di Giacomo M, et al. Herbicides glyphosate and glufosinate ammonium negatively affect human sperm mitochondria respiration efficiency[J]. Reproductive Toxicology, 2021, 99: 48-55.
[8] Menga A, Serra M, Todisco S, et al. Glufosinate constrains synchronous and metachronous metastasis by promoting anti‐tumor macrophages[J]. EMBO Molecular Medicine, 2020, 12(10): EMMM201911210.