Protection from hepatic ischemia/reperfusion injury and improvement of liver regeneration by alpha-lipoic acid.
The aim of this study was to characterize the in vivo action of lipoic acid (LA) in hepatic ischemia/reperfusion injury (IRI) and its effects on liver regeneration involving the investigation of mechanisms of action and effects on animal survival. Two groups of rats were compared: one group received 500 micromol alpha-LA injected via the inferior vena cava 15 min before the induction of 90 min of selective ischemia. The untreated group received vehicle. Influence of LA on IRI of the liver was determined in short- and long-term experiments. Cellular damage was decreased under preconditioning conditions with LA. Caspase 3, 8, and 9 activities were significantly lower in the LA group accompanied by a decrease in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes. Electron micrographs in the untreated group showed massive mitochondrial damage. The survival rate as end point of liver function was markedly increased after pretreatment with LA. Increased levels of tumor necrosis factor alpha was shown by enzyme-linked immunosorbent assay as well as real-time reverse transcription-polymerase chain reaction in the LA group accompanied by increased mitotic index and Ki-67 staining in liver tissue. Attenuation of IRI of the rat liver in vivo by LA is accompanied by reduction of necrosis and apoptosis-related cell death, whereas liver regeneration is increased.
Duenschede
Friedrich
F
Department of General and Abdominal Surgery, University Hospital Mainz, Mainz, Germany. duenschede@ach.klinik.uni-mainz.de
Erbes
Kirsten
K
Kircher
Achim
A
Westermann
Stefanie
S
Schad
Arno
A
Riegler
Nina
N
Ewald
Patrick
P
Dutkowski
Philipp
P
Kiemer
Alexandra K
AK
Kempski
Oliver
O
Junginger
Theodor
T
D000818:Animals; D017209:Apoptosis; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D022781:Hepatocytes / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008099:Liver / Q000473:pathology* / Q000502:physiology; D008115:Liver Regeneration; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury; D008063:Thioctic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019394:Ki-67 Antigen; D014409:Tumor Necrosis Factor-alpha; D008063:Thioctic Acid