Sexual dimorphism in endotoxin susceptibility after partial hepatectomy in rats.
OBJECTIVE
Liver failure due to endotoxemia after hepatectomy is a fatal complication. Little is known regarding the gender influence on this pathophysiological condition. This study was conducted to investigate whether a gender difference exists in the endotoxin susceptibility after hepatectomy.


METHODS
Sexually mature male and female rats received an intravenous administration of lipopolysaccharide (LPS), as endotoxin, 48h after a two-thirds hepatectomy.


RESULTS
The 24-h survival rate after LPS administration was significantly higher in females (75%) than in males (38%). Ovariectomy reduced the survival rate in females to 44%. Plasma tumor necrosis factor-alpha levels 1h after LPS were significantly elevated in males and ovariectomized females. The inducible nitric oxide synthase (iNOS) gene expression in liver and spleen, and consequent nitric oxide production 3h after LPS were significantly enhanced in males and ovariectomized females when compared to females, in addition to less functional and structural liver damage in females.


CONCLUSIONS
Our results indicate a gender difference in the susceptibility to endotoxemia in the early phase after hepatectomy. Female tolerance to these conditions may be mediated by an inhibition of excessive inflammatory response in the liver and the spleen, partially via the suppression of iNOS gene up-regulation.
Inaba
Keisuke
K
Second Department of Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. kinaba@hama-med.ac.jp
Suzuki
Shohachi
S
Ihara
Hayato
H
Sakaguchi
Takanori
T
Baba
Satoshi
S
Urano
Tetsumei
T
Konno
Hiroyuki
H
Nakamura
Satoshi
S
D000818:Animals; D001663:Bilirubin / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D006498:Hepatectomy; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000473:pathology / Q000502:physiology; D017093:Liver Failure / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013154:Spleen / Q000473:pathology / Q000502:physiology; D015996:Survival Rate; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D000637:Transaminases; D001663:Bilirubin