Pyridaben induces apoptosis and inflammation in bovine mammary epithelial cells by disturbance of calcium homeostasis and upregulation of MAPK cascades.

Pyridaben is a widely used pyridazinone insecticide used to protect crops against insects and mites. The toxicity of pyridaben has been reported in mice, zebrafish, the human reproductive system, nervous system, and respiratory system. Pyridaben can also be ingested by dairy cattle through feed. However, the toxicity of pyridaben in cattle has not been investigated on. Thus, this study focuses on demonstrating the toxicity of pyridaben in the bovine mammary glands and with the generation milk in the bovine mammary epithelial cells, as it is crucial to the continuance of the amount and the quality of the milk produced. We started by analyzing the intracellular toxicity along with the impact of pyridaben on the cell cycle distribution and the transcription of associated genes. Pyridaben treatment induced cell cycle arrest accompanied the disruption in G1 and S phases with imbalanced cytosolic and mitochondrial calcium ion homeostasis, and caused a destruction of mitochondrial membrane potential. This eventually led to apoptosis of MAC-T cells. We also investigated in the impact that pyridaben has on MAPK signaling proteins, where phosphorylation of ERK1/2, JNK, and p38 were upregulateed. Moreover, examination of the effect of pyridaben in the inflammatory genes revealed hyperactivation of the inflammatory gene transcription. This is the first research to assess the negative outcomes that pyridaben could impose on dairy cattle and milk production.

Dimethenamid promotes oxidative stress and apoptosis leading to cardiovascular, hepatic, and pancreatic toxicities in zebrafish embryo.

Dimethenamid, one of the acetamide herbicides, is widely used on soybeans and corns to inhibit weed growth. Although other acetamide herbicides have been reported to have several toxicities in non-target organisms including developmental toxicity, the toxicity of dimethenamid has not yet been studied. In this research, we utilized the zebrafish animal model to verify the developmental toxicity of dimethenamid. It not only led to morphological abnormalities in zebrafish larvae but also reduced their viability. ROS production and inflammation responses were promoted in zebrafish larvae. Also, uncontrolled apoptosis occurred when the gene expression level related to the cell cycle and apoptosis was altered by dimethenamid. These changes resulted in toxicities in the cardiovascular system, liver, and pancreas are observed in transgenic zebrafish models including fli1a:EGFP and L-fabp:dsRed;elastase:GFP. Dimethenamid triggered morphological defects in the heart and vasculature by altering the mRNA levels related to cardiovascular development. The liver and pancreas were also damaged through not only the changes of their morphology but also through the dysregulation in their function related to metabolic activity. This study shows the developmental defects induced by dimethenamid in zebrafish larvae and the possibility of toxicity in other non-target organisms.

Developmental toxicity of flufenacet including vascular, liver, and pancreas defects is mediated by apoptosis and alters the Mapk and PI3K/Akt signal transduction in zebrafish.

Release of agrochemicals from agricultural fields could unintentionally harm organisms that not targeted by pesticides. Flufenacet is one of the oxyacetamide herbicide applied in cultivation fields of crops and this has a possibility of unintentional exposure to diverse ecosystems including streams and surface water. Despite these environmental risks, limited information regarding toxicity of flufenacet on vertebrates is available. This study is aimed to assess environmental hazards and underlying toxic mechanisms of flufenacet by using a zebrafish model. Mortality measurements and morphological observations after the treatment of flufenacet suggested developmental toxicity of flufenacet in zebrafish. In addition, its toxicity on specific organs was evaluated using transgenic fluorescent zebrafish embryo. Adverse effects of flufenacet on vascular and hepatopancreatic development were demonstrated using Tg(flk1:EGFP) and Tg(fabp10a:DsRed; ela3l:EGFP) respectively. To address intracellular actions of flufenacet in zebrafish, cellular responses including apoptosis, cell cycle modulation, and Mapk and Akt signaling pathway were verified in transcriptional and protein levels. These results demonstrated developmental toxicity of flufenacet using the zebrafish model, providing essential information for assessing its potential hazards on vertebrates that are not directly targeted by the pesticide and for elucidating molecular mechanisms.