Drug Toxicology
Drug Toxicity studies are primarily used to
investigate specific adverse events and specific endpoints such as cancer, cardiotoxicity, and skin/eye
irritation. Drug discovery is implied here
to make a specialization drug of it. Patulin (PAT), a mycotoxin, is widespread in
agricultural products. Although available research results suggest that PAT can
be toxic to the nerves, immune system, and skin leading to heart, liver, and
kidney damage. Trypan blue staining and Hoechst 33342 staining were used to
analyze PAT, which induces apoptosis in 293 T cells. Superoxide dismutase
(SOD), GSH, and malondialdehyde (MDA) were used to measure changes in the state
Oxidative stress status of 293 T cells
induced by PAT. Changes in reactive oxygen species (ROS) and ATP in
mitochondria suggest a role for mitochondria when PAT induces cell damage and
apoptosis. Through analysis of Cyt-C release assay, alteration of caspase
activity, and correlation analysis, the potential mechanism of the mitochondrial apoptosis
pathway was demonstrated. The results demonstrated that PAT induced cell damage
significantly, and with increasing time and concentration, the cell survival
rate decreased significantly. Hoechst 33342 staining and Trypan blue staining
showed an increased rate of PAT-induced apoptosis. As PAT concentration
increased, the activities of intracellular SOD and glutathione peroxidase
decreased, and MDA content increased. Decreased intracellular ATP levels and
accumulated ROS content suggest increased mitochondrial membrane permeability.
Overexpression of Cyt-C triggered a cascade reaction of the enzyme caspase,
leading to apoptosis. The results of the enzyme activity assay and correlation
analysis indicated that caspase 3 was the most important in the cascade and was
most correlated with caspase 8 and caspase 9. Drug discovery helps to make
better medicinal components for this kind of effect.