Pharmaceutical research · 2003
Differential effect of acute hepatic failure on in vivo and in vitro P-glycoprotein functions in the intestine.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Yumoto Ryoko, Murakami Teruo, Takano Mikihisa
Аннотация
PURPOSE: The expression and function of P-glycoprotein (P-gp) in the intestine in carbon tetrachloride-induced acute hepatic failure (AHF) were evaluated in rats.
METHODS: The expression of P-gp, in vivo absorption and exsorption of P-gp substrates (digoxin and rhodamine 123), and in vitro efflux transport of these P-gp substrates were studied in the absence and presence of a P-gp inhibitor (verapamil or cyclosporin A) using the distal region of small intestine of control and AHF rats.
RESULTS: Western blot analysis revealed that intestinal P-gp expression level remained unchanged, or rather increased, in AHF. The in vivo intestinal P-gp function was significantly lower in AHF, as evaluated by the absorption and exsorption of P-gp substrates. In contrast, in vitro P-gp function was significantly higher in AHF, as evaluated by the efflux transport of P-gp substrates across the everted intestine. Collectively, the intestinal P-gp function was differently affected by AHF between in vivo and in vitro conditions.
CONCLUSIONS: The in vivo intestinal P-gp function was suppressed in AHF, which could not be predicted from in vitro functional studies nor from P-gp expression level. The discrepancy between in vivo and in vitro results may be explained by the presence of endogenous P-gp inhibitors in the plasma of AHF rats.
METHODS: The expression of P-gp, in vivo absorption and exsorption of P-gp substrates (digoxin and rhodamine 123), and in vitro efflux transport of these P-gp substrates were studied in the absence and presence of a P-gp inhibitor (verapamil or cyclosporin A) using the distal region of small intestine of control and AHF rats.
RESULTS: Western blot analysis revealed that intestinal P-gp expression level remained unchanged, or rather increased, in AHF. The in vivo intestinal P-gp function was significantly lower in AHF, as evaluated by the absorption and exsorption of P-gp substrates. In contrast, in vitro P-gp function was significantly higher in AHF, as evaluated by the efflux transport of P-gp substrates across the everted intestine. Collectively, the intestinal P-gp function was differently affected by AHF between in vivo and in vitro conditions.
CONCLUSIONS: The in vivo intestinal P-gp function was suppressed in AHF, which could not be predicted from in vitro functional studies nor from P-gp expression level. The discrepancy between in vivo and in vitro results may be explained by the presence of endogenous P-gp inhibitors in the plasma of AHF rats.