Anoxic hepatocyte injury: Role of reversible changes in elemental content and distribution†

Abstract

Examination of anoxic isolated hepatocytes by light and electron microscopy indicated that initial morphologic changes were largely localized to the periphery of the cells. This early phase consisted of surface bleb formation but was not accompanied by alterations in parameters of plasma membrane integrity (leakage of cellular enzymes, exclusion of trypan blue). The time course of changes in structure was temporally related to alterations in the elemental distribution and content of various subcellular compartments. These studies, which employed electron probe X-ray microanalysis, demonstrated that rapid increases in the sodium and chlorine content and decreases in the potassium content of the cytoplasm, mitochondria and nucleus occurred, whereas no change in the calcium content of any subcellular compartment was detected. Concurrently, two cellular functions known to be dependent upon ion homeostasis, sodium-dependent taurocholate uptake and mitochondrial respiratory control, became markedly impaired. Reoxygenation within 30 min resulted in the restoration of both elemental distribution and the latter two functions to baseline. These data are consistent with the hypothesis that some early functional changes may be mediated by altered ion homeostasis. In contrast, additional studies indicated that sodium and water fluxes could be dissociated from the appearance of plasma membrane blebs. Thus, this study provides direct evidence that the structural and functional changes of early anoxic hepatocyte injury cannot be explained by a single mechanistic cascade, but apparently involve multiple mechanisms which may not be directly linked.

Quantification of the Expression of HIF-1alpha by Real-Time PCR in Rat Hepatocytes Cultures Invaded by <i>Shigella flexneri</i> under Normoxic and Hypoxic Conditions

“…Interestingly, S. flexneri invaded less hepatocytes under hypoxia, in agreement with other studies using different pathogens and cells [29]- [31]. Hypoxia can modify gene expression, intra and extracellular pH as well as membrane receptors [32]- [34]. We can speculate that these factors contributed to the lower entrance of bacteria into hepatocytes.…”

The central role of sinusoidal endothelial cells in hepatic hypoxia-reoxygenation injury in the rat

“…Other studies have also shown that reoxygenation before the rupture of plasma membrane blebs results in the rapid resorption of blebs and in the recovery of hepatocytes, rather than in the accentuation of cellular injury. [34][35][36][37] Conflicting results of the susceptibility of hepatocytes to hypoxia-reoxygenation have been reported by others, 38,39 but these experiments used hepatocyte suspensions which may not be relevant to the physi- cyte cell suspensions, 36,37,39 cells cultured for less than 22 hours, 34,38 or fasted rats as cell donors. 34 All these factors could be the cause of the suboptimal viability of cultured DISCUSSION hepatocytes because of effects on plasma membrane integrity and on antioxidant defences, particularly cellular glutathione In ischemia-reperfusion injury of the liver, the severity of hepatic damage exceeds that produced during a comparable levels.…”

Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers

“…Several findings implicate that the pathogenesis of hypoxic and toxic cell injury to hepatocytes involves intracellular Na C accumulation [1][2][3][4][5]. Total Na C content increases rapidly in all regions of hepatocellular cytoplasm during the first 30 min of anoxia [2].…”

“…Total Na C content increases rapidly in all regions of hepatocellular cytoplasm during the first 30 min of anoxia [2]. Moreover, hypoxia, hepatocyte cold storage, respiratory inhibition, uncoupling, the redox cycler menadione all cause an increase of intracellular Na C , which is followed by cell swelling and cell death [3][4][5].…”