Suppression of ischaemia-induced cytokine release by dimaprit and amelioration of liver injury in rats.
Inflammatory reactions play an important role in ischaemia/reperfusion injury in various organs. Since histamine H(4) action has been shown to prevent the development of ischaemia/reperfusion liver injury, we examined the effects of dimaprit, a histamine H(2)/H(4) receptor agonist, on ischaemia-induced cytokine release and liver damage. Male Wistar rats (300 g) were subjected to warm ischaemia for 30 min. by occlusion of the left portal vein and hepatic artery under halothane anaesthesia. Saline or dimaprit (20 mg/kg, subcutaneously) was injected immediately after reperfusion of blood flow. Transient ischaemia provoked severe liver damage 24 hr after reperfusion, and the plasma concentrations of alanine transaminase and aspartate transaminase were 4600 IU/l and 13,200 IU/l, respectively. The values in the dimaprit group were 55% and 46% of those in control animals, respectively. Dimaprit also reduced the infarct size to 50%. Liver ischaemia markedly increased interleukin-12 levels 2-24 hr after reperfusion. The dimaprit treatment depressed the values to 40-64% of those in the corresponding control group 4-24 hr after reperfusion. Since interleukin-12 facilitates cell-mediated cytotoxicity, the protective effect of dimaprit may be attributed to regulation of cytokine release during reperfusion.
Motoki
Atsuko
A
Department of Anaesthesiology and Resuscitology, Ehime University Graduate School of Medicine, Shitsukawa, Touon-shi, Ehime, Japan. atsumotoki@hotmail.com
Adachi
Naoto
N
Liu
Keyue
K
Takahashi
Hideo K
HK
Nishibori
Masahiro
M
Yorozuya
Toshihiro
T
Arai
Tatsuru
T
Nagaro
Takumi
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D017259:Dimaprit / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D015536:Down-Regulation; D006499:Hepatic Artery / Q000601:surgery; D006632:Histamine / Q000097:blood; D017442:Histamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018664:Interleukin-12 / Q000097:blood; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008026:Ligation; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D011169:Portal Vein / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D000074040:Receptors, Histamine H4; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013997:Time Factors
D016207:Cytokines; D017442:Histamine Agonists; C498828:Hrh4 protein, rat; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D000074040:Receptors, Histamine H4; D018664:Interleukin-12; D006632:Histamine; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017259:Dimaprit