Isolated perfused rat livers have been used for various studies, but detailed investigation into the structural integrity of hepatocytes of this system is lacking. In this study, isolated rat livers were perfused in vitro with oxygenated Krebs-Ringer bicarbonate buffer solution, for 2 minutes and 1, 2, 3, and 4 hour(s) at 37 degrees C, using a non-recirculating perfusion system. The perfused li...

Acetaminophen (N-acetyl para amino phenol, APAP) is a widely used antipyretic and analgesic drug responsible for various drug-induced liver injuries. This study evaluated APAP-induced toxicity in isolated rat hepatocytes alongside the protective effects of silafibrate and N-acetyl cysteine (NAC). Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via the por...

GKAs (glucokinase activators) are promising agents for the therapy of Type 2 diabetes, but little is known about their effects on hepatic intermediary metabolism. We monitored the fate of (13)C-labelled glucose in both a liver perfusion system and isolated hepatocytes. MS and NMR spectroscopy were deployed to measure isotopic enrichment. The results demonstrate that the stimulation of glycolysi...

We tested whether hepatic blood flow is altered following central hypovolemia caused by simulated orthostatic stress. After 30 min of supine rest, hemodynamic, plasma density, and indocyanine green (ICG) clearance responses were determined during and after release of a 15-min 40 mmHg lower body negative pressure (LBNP) stimulus. Plasma density shifts and the time course of plasma ICG concentrat...

Congestive heart failure has been shown to affect oxidative drug metabolism, however, there has been little study of its effects on drug conjugation. Using the isolated perfused livers from rats with right ventricular failure (RVF) due to pulmonary artery constriction, we studied the effects of RVF on hepatic elimination of p-nitrophenol (PNP) under controlled flow and oxygen delivery condition...

(cGMP). Like NO , CO can also activate guanylate cyclase to cause vasodilation [5] ; however, previous studies have indicated that other mechanisms may contribute to the effects of CO on hepatic tone [6] . In their study [4] , the authors found some potentially novel mechanisms by which HO-1 mediates hepatic tone that appear independent of cGMP and, at least in part, independent of CO . The aut...

We examined the effects of hypoxia and reoxygenation in isolated, perfused rat livers. Hypoxia induced by a low rate of perfusion led to near anoxia confined to centrilobular regions of the liver lobule. Periportal regions remained normoxic. Within 15 min, anoxic centrilobular hepatocytes developed surface blebs that projected into sinusoids through endothelial fenestrations. Periportal hepatoc...

Rats fed a bean diet develop a significant hypocholesterolemia. The catabolism of low density lipoprotein (LDL; d 1.019-1.063 g/ml) was studied in vivo and in vitro in the isolated perfused liver of rats fed either a casein or a bean diet. The clearance of LDL was significantly increased by 100% from 0.38 +/- 0.04 to 0.63 +/- 0.04 ml/h x 100 g body wt in vivo in the bean-fed rat. Similarly, the...