Ischaemic preconditioning modulates the activity of Kupffer cells during in vivo reperfusion injury of rat liver.
This work was performed to elucidate further the main cellular events underlying the protective effect of ischaemic preconditioning in an in vivo rat liver model of 90 min ischaemia followed by 30 min reperfusion. A significant attenuation of the various aspects of post-ischaemic injury, namely necrosis and the levels of hydrogen peroxide and 5- and 15-hydroperoxyeicosatetraenoic acids, was afforded by the prior application of a short cycle of ischaemia/reperfusion (10 + 10 min) or when rats were previously treated with gadolinium chloride. However, when preconditioning was applied on Kupffer cell-depleted livers, no additional level of ischaemic tolerance was obtained. In terms of cellular pathology, this result could be suggestive of Kupffer cells as the target of the preconditioning phenomenon during the warm ischaemia/reperfusion injury. Accordingly, modulation of Kupffer cell activity was associated with a well-preserved hepatocyte integrity, together with low levels of pro-oxidant generation during reperfusion. As activated Kupffer cells can generate and release potentially toxic substances, their modulation by ischaemic preconditioning could help to provide new surgical and/or pharmacological strategies to protect the liver against reperfusion damage.
Cavalieri
Barbara
B
Laboratory of Experimental Liver Pathology, Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Turin, Italy.
Perrelli
Maria-Giulia
MG
Aragno
Manuela
M
Ramadori
Pierluigi
P
Poli
Giuseppe
G
Cutrìn
Juan C
JC
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D019194:Ischemic Preconditioning / Q000379:methods*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D015289:Leukotrienes / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012965:Sodium Chloride / Q000494:pharmacology; D000637:Transaminases / Q000097:blood
D015289:Leukotrienes; D008054:Lipid Peroxides; D012965:Sodium Chloride; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025348:arachidonic acid 5-hydroperoxide; D005682:Gadolinium; D006861:Hydrogen Peroxide; D001094:Arachidonate 5-Lipoxygenase; D000637:Transaminases; C038958:gadolinium chloride