Picroliv preconditioning protects the rat liver against ischemia-reperfusion injury.
Cell death following ischemia-reperfusion injury is a major concern in clinical issues such as organ transplantation and trauma. The need to identify agents with a potential for preventing such damage has assumed great importance. We have evaluated the efficacy of picroliv, a potent antioxidant derived from the plant Picrorhiza kurrooa, in protecting against hepatic ischemia-reperfusion injury in vivo. Picroliv was fed to male Sprague Dawley rats in a dose of 12 mg/kg once daily by oral gavage for 7 days prior to hepatic ischemia. Ischemia was induced by occluding the hepatic pedicel with a microaneurysm clip for 30 min and reperfusion was allowed thereafter for varying period (15-120 min) by releasing the microaneurysm clip. Picroliv pretreatment resulted in better hepatocyte glycogen preservation and reduced apoptosis. Reduction in apoptosis was associated with decreased mRNA expression of caspase-3 and Fas. Oxidant induced cellular damage as measured by tissue malondialdehyde (MDA) levels was significantly less following picroliv pretreatment. Both a reduction in neutrophil infiltration and an increased level of intracellular antioxidant enzyme superoxide dismutase possibly contributed to the reduction in tissue lipid peroxidation. Tissue inflammatory cytokines level of interleukin-1alpha (IL-1alpha) and interleukin-1beta (IL-1beta) was also lower in picroliv group. Furthermore, picroliv pretreatment resulted in enhanced proliferating cell nuclear antigen (PCNA) immunoreactivity. These studies strongly suggest picroliv to be a promising agent for ameliorating injury following ischemia-reperfusion.
Singh
A K
AK
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Mani
H
H
Seth
P
P
Gaddipati
J P
JP
Kumari
R
R
Banuadha
K K
KK
Sharma
S C
SC
Kulshreshtha
D K
DK
Maheshwari
R K
RK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1 / Q000235:genetics; D053143:Caspase 2; D020169:Caspases / Q000235:genetics; D002934:Cinnamates / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008112:Liver Glycogen / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014641:Vanillic Acid / Q000494:pharmacology*
D002934:Cinnamates; D006027:Glycosides; D007375:Interleukin-1; D008112:Liver Glycogen; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C057463:kutkin; D009195:Peroxidase; D013482:Superoxide Dismutase; D053143:Caspase 2; D020169:Caspases; D020170:Caspase 1; D014641:Vanillic Acid