Single injection of naked plasmid encoding alpha-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice.
Oxidative stress has been implicated in the propagation of acute liver injury. The aim of our study was to investigate whether gene transfer of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory peptide, could prevent fulminant hepatic failure in mice. Acute liver damage was induced by intraperitoneal administration of thioacetamide. Hydrodynamics-based gene transfection with alpha-MSH expression plasmid via rapid tail vein injection was initiated 1 day prior to intoxication. The mortality in the alpha-MSH-treated mice was significantly lower compared to the vehicle group 3 days after injury. Liver histology significantly improved and TUNEL-positive hepatocytes decreased in the treated mice. The degradation of IkappaBalpha, endogenous inhibitor of nuclear factor kappaB, and upregulation of inducible nitric oxide synthase and tumor necrosis factor-alpha mRNA levels were prevented in the alpha-MSH-treated group, indicating decreased oxidative stress and inflammation. These results suggest alpha-MSH gene therapy might protect against acute hepatic necroinflammatory damage with further potential applications.
Department of Anesthesiology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, ROC.
Cheng-Haung
CH
Wang
Bruno
B
Jawan
Tsung-Hsing
TH
Lee
Kuo-Sheng
KS
Hung
Wen-Ying
WY
Chou
Cheng-Nann
CN
Lu
Jong-Kang
JK
Liu
Yann-Jang
YJ
Chen
D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D007275:Injections, Intravenous; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics*; D015996:Survival Rate; D013853:Thioacetamide; D016896:Treatment Outcome; D000521:alpha-MSH / Q000097:blood* / Q000235:genetics*
D013853:Thioacetamide; D000521:alpha-MSH