Ethyl pyruvate prevents intestinal inflammatory response and oxidative stress in a rat model of extrahepatic cholestasis.
BACKGROUND
Ringer's ethyl pyruvate solution (REPS) has been shown to ameliorate liver injury in a murine model of extrahepatic cholestasis. The goal of the present investigation was to gain additional information about whether infusing REPS instead of Ringer's lactate solution (RLS) after inducing obstructive jaundice would be beneficial to intestinal barrier function, inflammatory response, and oxidative stress.


METHODS
Male Sprague Dawley rats were divided into three groups: Group Sham (n=6), sham-treated controls; Group RLS (n=9), common bile duct ligation (CBDL) plus RLS; and Group REPS (n=9), CBDL plus REPS. On 14 d after BDL, the rats were sacrificed and intestinal permeability was analyzed. Ileal IL-6 and TNF-alpha levels, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), and NF-kappaB activity were determined. Histologic examination and apoptosis of ileum were also examined.


RESULTS
Relative to sham-treated controls, CBDL in RLS-treated rats were associated with increased intestinal permeability to FITC-labeled dextran (4.51+/-0.85 versus 0.44+/-0.18, P<0.01), histopathologic damage and apoptosis (68.4+/-13.4 versus 6.7+/-1.9 pre-1000 villi cells, P<0.01). IL-6 and TNF-alpha level, MDA, MPO, and NF-kappaB activity in ileal tissues were also promoted, along with decreased GSH levels. Treatment with REPS significantly decreased intestinal permeability (3.37+/-0.71, P<0.01) and apoptosis (42.8+/-14.3 pre-1000 villi cells, P<0.01). Other changes were also significantly attenuated by treatment with REPS after CBDL.


CONCLUSIONS
The present study demonstrates that administration of REPS, but not RLS, maintains intestinal barrier function and reduces intestinal oxidative damage, inflammatory response, and apoptosis in cholestatic rats. This effect of ethyl pyruvate may be useful for preventing intestinal injury in patients with biliary obstruction.
Wang
Pengfei
P
Department of Intensive Care Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Gong
Guanwen
G
Wei
Zhiqing
Z
Li
Yousheng
Y
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004751:Enteritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D041781:Jaundice, Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D015850:Interleukin-6; D016328:NF-kappa B; D011773:Pyruvates; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D008315:Malondialdehyde; D009195:Peroxidase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D001663:Bilirubin