Kupffer cell inhibition and its effect on ischemia/reperfusion injury as well as the biotransforming potential of the liver
Ryszard Wiaderkiewicz, Anna Wiaderkiewicz, Danuta Plewka, Marcin Kamiński, Artur Caban, Grzegorz Oczkowicz, Stanisław Kuśmierski
Med Sci Monit 1999; 5(6): BR1074-1080
Available online: 1999-11-01
Kupffer cells are believed to play an important role during ischemia-reperfusion (IR) injury of the liver, mostly by releasing pro-inflammatory factors and oxygen free radical formation. In our study we investigated the effect of pharmacological Kupffer cell inhibition by gadolinium chloride (GdCl3 Ð a selective Kupffer cell toxicant) on IR injury, as well as the biotransforming potential of the liver intoxicated with the organophosphorous insecticide Ð chlorfenvinphos. The study was performed on rats divided into 6 groups. Group 1 served as the control. Group 2 rats were subjected to 60 min of ischemia followed by 24 hours of reperfusion (I/R). Group 3 rats received chlorfenvinphos (i.p. Ð 2 mg/kg body weight) and were sacrificed after 24 hours. Group 4 rats received chlorfenvinphos after 30 min of ischemia and were sacrificed after 24 hours of reperfusion. Group 5 rats were subjected to I/R and GdCl3 was injected (i.v.) prior to reperfusion. Group 6 comprised rats subjected to I/R, treated with GdCl3 as mentioned above and injected with chlorfenvinphos. Liver sections were evaluated morphologically (H&E staining) and histochemically (SDH, LDH, G6Pase, Mg+2 ATPase and AcP activity). We evaluated the total content of cytochromes P450 and b5, activities of their corresponding NADPH and NADH reductases, as well as the presence of CYP1A1, CYP2E1 and CYP2B1/B2 isoforms in the microsomal fraction of the liver. I/R affects all studied enzyme activities and reduces the cytochrome P450 content and activity of its NADPH reductase. Amongst the studied isoforms, CYP2B1/B2 are mostly affected by IR. Intraperitoneal injection of chlorfenvinfos alone caused slight damage to the liver, although dramatically affected all studied parameters in rats subjected to I/R. The injection of gadolinium chloride alone has no effect on the structure nor biotransforming potential of the liver. However, the injection of GdCl3 prior to reperfusion demonstrated a beneficial effect on the activity of marker enzymes and diminished the morphological liver changes caused by I/R.
Keywords: P450 isoforms, Kupffer cells, gadolinium chloride, Reperfusion, Ischemia