Alterations in the Content of Metal Elements and Fatty Acids in Hepatic Ischaemia–Reperfusion: Induction of Apoptotic and Necrotic Cell Death

Abstract

Ischaemia and reperfusion are related to oxidative stress, which alters with the redox-homeostasis of the liver cells. Our aim was to reveal the correlations between changes of metal element and fatty acid concentration (two main components of redox-balance) and apoptotic and necrotic processes of hepatic ischaemia-reperfusion. Wistar rats were divided into three groups: control, sham-operated and reperfusion. Hepatic ischaemia was induced for 45 min in the left lateral, left medial and right medial lobes followed by 24 h of reperfusion. Global redox parameters and glutathione peroxidase and superoxide dismutase activity were detected by luminometry and spectrophotometry. Routine laboratory measurements, fatty acid composition (with gas chromatography) as well as metal ion concentration of liver (with ICP-OES) were determined. Metallothionein activity was measured by atomic absorption spectrometry. Immunohistochemical and histological examinations were carried out to investigate apoptotic and necrotic changes in the liver. During reperfusion, global antioxidant parameters decreased and superoxide dismutase level of the liver was significantly lower than in the sham-operated group. Changes in the metal element concentration are essential for cellular biochemical pathways, and significant correlations were found between decrease in Cu and Zn content and decreased superoxide dismutase activity. Necrotic lesions along with increased number of apoptotic cells were found in the liver after 24 h of reperfusion. Alterations in the metal element and fatty acid content was found in the liver tissue during 24 h of ischaemia-reperfusion along with increase in the number of apoptotic cells and significant disturbance of the antioxidant balance. Study of the metal element content of the liver during hepatic ischaemia-reperfusion may provide new supportive strategies for liver surgery and transplantation.

Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation

“…Anoxiahypoglycemia in organotypic hippocampal cultures demonstrated that zinc can inhibit glutamate release via activation of pre-synaptic K ATP channels and reduce ischaemic damage in rat hippocampus (Bancila et al 2004). Interestingly, the level of zinc and metallothionein was found to decrease during ischemia-reperfusion injury, implying a possible role for enhanced apoptosis and significant disturbance in redox balance in hepatic ischemia (Vali et al 2008). Thus, evidence obtained so far suggests that zinc preconditioning is a complex process and involves a spectrum of mechanisms involving intracellular and intercellular transients of zinc, ability to induce metallothionein, a potential scavenger of hydroxyl radicals and the ability of zinc per se to act as a major signaling molecule, triggering a cascade of events that are both redox-dependent and independent.…”

The beneficial effect of metadoxine (pyridoxine-pyrrolidone-carboxylate) in the treatment of fatty liver diseases

“…Protection against necrosis is a well-defined aim of liver surgery, whereas the inhibition of apoptosis may have negative effects on patients undergoing surgery for hepatic cancer. Our short-term model can give new perspectives of the metadoxine treatment [68].…”