Dihydrolipoyl histidinate zinc complex, a new antioxidant, attenuates hepatic ischemia-reperfusion injury in rats.
OBJECTIVE
Ischemia/reperfusion (I/R) injury is characterized by significant oxidative stress, which induces characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. The aim of this study was to evaluate the protective effect of dihydrolipoyl histidinate zinc complex (DHLHZn) on oxidative damage after severe hepatic I/R injury.


METHODS
Thirty male Wistar rats were subjected to 45 min of hepatic ischemia by clamping of the hepatic artery and portal vein, followed by a 6-h reperfusion period. DHLHZn (10 mg/kg) (I/R + DHLHZn group) or saline (I/R group) was administered intraperitoneally twice, 30 min before ischemia and at the beginning of the reperfusion. Sham-operated animals (sham group) received equal amounts of saline. The rats were killed at the end of the reperfusion period. Serum levels of aspartate aminotransferase and alanine aminotransferase were determined, and histological examination and oxidative stress were evaluated in liver tissues. In addition, antimycin A-stimulated RAW264.7 cells (murine macrophage-like cells) were treated with DHLHZn to estimate its antioxidant effect.


RESULTS
Serum aspartate aminotransferase and alanine aminotransferase levels were increased in the I/R group, but these increases were significantly inhibited in the I/R + DHLHZn group. Similarly, liver tissue damage observed in the I/R group was attenuated in the I/R + DHLHZn group. Cells treated in vitro with both DHLHZn and antimycin A showed reduced reactive oxygen species activity compared to cells treated with antimycin A alone.


CONCLUSIONS
The new antioxidant DHLHZn may have potential for therapeutic application in liver I/R injury, although this is a limited animal study.
Department of Surgery I, Oita University Faculty of Medicine, Oita, Japan. tmasuda@oita-u.ac.jp
Takashi
T
Masuda
Yukio
Y
Iwashita
Satoshi
S
Hagiwara
Masayuki
M
Ohta
Masafumi
M
Inomata
Takayuki
T
Noguchi
Seigo
S
Kitano
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000737:chemistry; D002460:Cell Line; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
D000975:Antioxidants; D015415:Biomarkers; D001713:Biphenyl Compounds; D010851:Picrates; D017382:Reactive Oxygen Species; C557205:dihydrolipoylhistidine; D006639:Histidine; D008315:Malondialdehyde; D000968:Antimycin A; D008063:Thioctic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase