3D model elucidates acetaminophen toxicity in hepatic cells
2019
Maastricht University, Maastricht, Netherlands
Inflammation may have a role in the acetaminophen-mediated toxicity of hepatic cells. Here, a 3D co-culture of human primary hepatocytes and Kupffer cells was treated with acetaminophen to evaluate its toxicity with or without lipopolysaccharide challenge. The results showed that acetaminophen can inhibit the expression of genes involved in metabolic homeostasis and anti-oxidant functions. Moreover, higher doses of acetaminophen hindered Fc fragment receptor genes even without lipopolysaccharide. Also, toll-like receptor 4 expression was elevated after double treatment, which could reduce Kupffer cells phagocytosis and disrupt cytokine expression. Furthermore, co-exposure to inflammatory challenge and acetaminophen led to a pro-inflammatory cytokine profile. Overall, the researchers validate a new 3D model for drug testing and elucidate inflammation-mediated drug toxicity mechanisms of acetaminophen.
Human 3D multicellular microtissues: An upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity
J Jiang
Added on: 11-28-2021
[1] https://www.sciencedirect.com/science/article/pii/S0378427419301377
