Inosine improves gut permeability and vascular reactivity in endotoxic shock.
OBJECTIVE
To investigate the effects of inosine administration on vascular reactivity, gut permeability, neutrophil accumulation and lipid peroxidation in tissues in murine endotoxin shock.


METHODS
Randomized, prospective laboratory study.


METHODS
Research laboratory.


METHODS
BALB/c mice 6-8 wks age.


METHODS
BALB/c mice were randomly assigned to one of five groups: a) vehicle controls, which received saline intraperitoneally; b) inosine controls, which received inosine alone (100 mg/kg, ip); c) lipopolysaccharide (LPS)-treated animals, which received LPS (40 and 100 mg/kg, ip, depending on the experimental protocol); d) inosine pretreatment group, which received inosine (100 mg/kg, ip) 30 mins before LPS; and finally, e) inosine posttreatment group, which received inosine (100 mg/kg, ip) 60 mins after LPS.


RESULTS
The passage of fluorescein isothiocyanate-conjugated dextran (4 kDa, FD4) was analyzed in everted gut ileal sacs incubated ex vivo as an index of gut permeability. LPS induced a significant intestinal hyperpermeability, and inosine exerted protective effects both in pre- and posttreatment regimens. Myeloperoxidase and malondialdehyde were also measured to study neutrophil accumulation and lipid peroxidation in selected tissues. Inosine, both in pre- and posttreatment regimens ameliorated the increases in myeloperoxidase and malondialdehyde in the lung and gut. LPS-treated animals showed decreased contractile and relaxant responses, and inosine pretreatment (but not posttreatment) partially improved these responses.


CONCLUSIONS
Taken together, inosine has organ protective effects during shock. A significant portion of its protective action is maintained even in the posttreatment scenario.
Garcia Soriano
F
F
Inotek Corporation, Beverly, MA, USA.
Liaudet
L
L
Marton
A
A
Haskó
G
G
Batista Lorigados
C
C
Deitch
E A
EA
Szabó
C
C
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D007288:Inosine / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D012772:Shock, Septic / Q000188:drug therapy*
D008070:Lipopolysaccharides; D008315:Malondialdehyde; D007288:Inosine; D009195:Peroxidase