Role of Oil Vehicle on Hepatic Cell Proliferation in PCB-Treated Rats

Abstract

Here we report the role of dietary glycine and the type of oil used as a vehicle on hepatotoxicity in 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB-153)-treated or control rats. In the first study, glycine or valine (as control) was fed in an unrefined diet at 5% for the entire study (5 days) to inhibit Kupffer cell activity. PCB-153 (100 or 300 µmol/kg) dissolved in medium chain triglyceride (MCT) oil, was injected i.p. two days before euthanasia; the peroxisome proliferator Wy-14,643 was included as a positive control. MCT oil decreased cell proliferation by about 50%. PCB-153 slightly increased hepatic cell proliferation, but dietary glycine did not reduce cell proliferation. Because of the inhibition of cell proliferation in rats receiving MCT oil compared to rats receiving no injection, we hypothesized that MCT oil may have been inhibiting the hepatocyte proliferation in PCB-153-treated rats. We therefore performed another experiment using three types of oil as a vehicle for PCB-153: MCT oil, corn oil and olive oil. Rats were injected with PCB-153 (300 µmol/kg) or one of the vehicles, again two days before euthanasia. MCT oil again decreased the hepatocyte proliferation by about 50%. In rats receiving PCB-153, hepatocyte proliferation was slightly higher than their respective vehicle controls for corn oil and olive oil but not for MCT oil. These studies show that the oil vehicle is important in cell proliferation after PCB exposure, with MCT oil appearing to be protective.

Retinoid Chemoprevention: Who Can Benefit?

“…This is not unexpected as retinoids are lipid soluble, however it is an often ignored detail in retinoid clinical trials. Additionally, we and others have reported that different oils have different effects on cell proliferation or differentiation, endpoints often targeted by retinoid chemoprevention [100-104]. This points to the need of future studies of retinoid cellular and systemic effects and mechanism of action where other relevant factors such as diet are carefully controlled.…”