Biochemical Alterations and Endothelial Dysfunction in Hypercholesterolemic Rats: Effects of Bezafibrate

Abo-Zaid, Omayma Ahmed; Hasanin, Mohamed Ragaei Ragab; Hanafi, Amal

doi:10.5455/jib.20130305012038

Cited by 1 publication

(1 citation statement)

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“…Hepatocytes were incubated in an incubator (3% CO 2 ) at 23 °C for 48 h. After 24 h of culture, 90% of the medium was removed and replaced with fresh appropriate medium. Concentrations of DiDP were chosen on the basis of molecular docking analysis and taking into account the doses of obesogens that are known to activate PPAR in the regulation of glucose and FA metabolism. − Exposure of primary sea bream hepatocytes was performed using 24-well plates, and six independent wells were setup for both the control and each concentration of DiDP. The entire experiment was repeated 3 times.…”

Section: Methodsmentioning

confidence: 99%

Effects of Diisodecyl Phthalate on PPAR:RXR-Dependent Gene Expression Pathways in Sea Bream Hepatocytes

Cocci

Mosconi

Arukwe

et al. 2015

Chem. Res. Toxicol.

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Evidence that endocrine-disrupting chemicals (EDCs) may target metabolic disturbances, beyond interference with the functions of the endocrine systems has recently accumulated. Among EDCs, phthalate plasticizers like the diisodecyl phthalate (DiDP) are commonly found contaminants of aquatic environments and have been suggested to function as obesogens by activating peroxisome proliferator activated receptors (PPARs), a subset of nuclear receptors (NRs) that act as metabolic sensors, playing pivotal roles in lipid homeostasis. However, little is known about the modulation of PPAR signaling pathways by DiDP in fish. In this study, we have first investigated the ligand binding efficiency of DiDP to the ligand binding domains of PPARs and retinoid-X-receptor-α (RXRα) proteins in fish using a molecular docking approach. Furthermore, in silico predictions were integrated by in vitro experiments to show possible dose-relationship effects of DiDP on PPAR:RXR-dependent gene expression pathways using sea bream hepatocytes. We observed that DiDP shows high binding efficiency with piscine PPARs demonstrating a greater preference for RXRα. Our studies also demonstrated the coordinate increased expression of PPARs and RXRα, as well as their downstream target genes in vitro. Principal component analysis (PCA) showed the strength of relationship between transcription of most genes involved in fatty acid metabolism and PPAR mRNA levels. In particular, fatty acid binding protein (FABP) was highly correlated to all PPARs. The results of this study suggest that DiDP can be considered an environmental stressor that activates PPAR:RXR signaling to promote long-term changes in lipid homeostasis leading to potential deleterious physiological consequences in teleost fish.

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Section: Methodsmentioning

confidence: 99%