Molecular modelling of phthalates - PPARs interactions.
Di(2-ethylhexyl) phthalate (DEHP) is the most widely plasticizer for polyvinyl chloride (PVC) that is used in plastic tubes, in medical and paramedical devices as well as in food storage packaging. The toxicological profile of DEHP has been evaluated in a number of experimental animal models and has been extensively documented. Its toxicity is in part linked to the activation of the peroxisome proliferator-activated receptor alpha (PPAR(alpha)). As a response, an intensive research for a new, biologically inert plasticizer has been initiated. Among the alternative studied, tri(2-ethylhexyl) trimellitate (TEHTM) or trioctyl trimellitate (TOTM) has attracted increasing interest. However, very little information is available on their biological effects. We proceeded to dock TOTM, DEHP and its metabolites in order to identify compounds that are likely to interact with PPAR(alpha) and PPAR(gamma) binding sites. The results obtained hint that TOTM is not able to bind to PPARs and should therefore be safer than DEHP.
Kambia
Nicolas
N
Laboratoire de Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Lille Cedex, France.
Renault
Nicolas
N
Dilly
Sebastien
S
Farce
Amaury
A
Dine
Thierry
T
Gressier
Bernard
B
Luyckx
Michel
M
Brunet
Claude
C
Chavatte
Philippe
P
D001565:Benzoates / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008958:Models, Molecular; D047493:PPAR alpha / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010795:Phthalic Acids / Q000737:chemistry* / Q000633:toxicity; D010968:Plasticizers / Q000737:chemistry / Q000633:toxicity; D011485:Protein Binding
D001565:Benzoates; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D010795:Phthalic Acids; D010968:Plasticizers; C036101:tri-(2-ethylhexyl)trimellitate; C034367:trioctyl trimellitate