Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats.
BACKGROUND
Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.


METHODS
120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg.kg-1, CS 50 mg.kg-1, and CP 0.75 mg.kg-1 i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3rd day after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 of the small intestine were detected at the same time.


RESULTS
Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-alpha in intestine increased significantly compared with group S (P < 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (P < 0.05), attenuated the down-regulation or up-regulation of the above index (P < 0.05). Treatment with CP decreased the survival rate on the 3rd day after reperfusion compared with group M(P < 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(P > 0.05).


CONCLUSIONS
Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.
Hei
Zi-qing
ZQ
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China. heiziqing0530@hotmail.com
Gan
Xiao-liang
XL
Huang
Pin-jie
PJ
Wei
Jing
J
Shen
Ning
N
Gao
Wan-ling
WL
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D007665:Ketotifen / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000401:mortality* / Q000517:prevention & control; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D006634:Histamine H1 Antagonists; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003189:p-Methoxy-N-methylphenethylamine; D004205:Cromolyn Sodium; D007665:Ketotifen