Investigation of steatosis profiles induced by pesticides using liver organ-on-chip model and omics analysis

Effect of Pesticides on Peroxisome Proliferator-Activated Receptors (PPARs) and Their Association with Obesity and Diabetes

“…In a study using the latest technology proposing organ replacement using an organ-on-chip of a rat kidney, the transcriptome and metabolome were analyzed after DDT and permethrin exposure and their mixture. The results show that the conditions assessed produced a hepatic steatosis profile with high expression of PPAR-related genes, fatty acids, lipid metabolism, and steroid biosynthesis; and the mixture had an additive effect on the transport RNA and necrotic/inflammatory profiles [36].…”

“…The changes induced by the activation of PPARs due to interaction with pesticides have been linked to the development of obesity and type 2 diabetes mellitus [34,35]. The analysis is mainly based on the findings of differentially expressed genes (DEGs) [36] and transcription factors (TFs) [37], which are the main group of proteins that have a response to the exposure of a chemical substance and specifically increase biological conditions; the result can be associated through networks that allow to identify central and key genes in many diseases [29]. Alteration of PPARγ expression in the presence of toxaphene, methoxychlor, permethrin, atrazine, DDT, paraquat, and chlorpyrifos was described in microarray (RNA) analysis in a rat hepatocyte model, revealing changes in lipid and carbohydrate metabolism [37].…”

Microfluidics: a concise review of the history, principles, design, applications, and future outlook

“…Researchers have developed organ-on-chip models (Fig. 14) for the brain, 208,209 gut, 207,210 heart, 211,212 eyes, 213,214 muscle, 215 lungs, 216,217 liver, 218,219 skin, 220 blood vessels, 221 etc.…”

Liver organ-on-chip models for toxicity studies and risk assessment

“…Furthermore, transcriptome modulation reflected liver inflammation, steatosis, necrosis, PPAR signalling and fatty acid metabolism. 188,192,193 Rotenone is a widely used organic pesticide known to induce oxidative stress and the mitochondrial dysfunction involved in the pathogenesis of Parkinson's disease. 194,195 Bavli et al developed a liver-on-chip model capable of maintaining 3D aggregates of HepG2/C3A cells for 28 days while monitoring oxygen uptake, glucose uptake, and lactate production rates over the same period.…”