The effect of α-melanocyte stimulating hormone on endotoxin-induced intestinal injury

We investigated the effect of α-melanocyte stimulating hormone (α-MSH) on endotoxin-induced intestinal inflammation and the role of nitric oxide and prostaglandins in this response. α-MSH treatment (25 μg/rat, intraperitoneally (i.p.); twice daily) reduced the severity of the lesions macroscopically...

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Published inPeptides (New York, N.Y. : 1980) Vol. 22; no. 12; pp. 2077 - 2082
Main Authors Şan, Tangül, Oktar, Berna K., Salik, Emsal, Ercan, Feriha, Alican, İnci
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.12.2001
Subjects
alpha-MSH - pharmacology
Animals
Cyclooxygenase Inhibitors - pharmacology
Endotoxemia
Female
Indomethacin - pharmacology
Intestines - drug effects
Intestines - enzymology
Intestines - injuries
Lipopolysaccharides - toxicity
Male
Microscopy, Electron, Scanning
Neutrophils
Nitric oxide
Prostaglandins
Rats
Rats, Sprague-Dawley
Sulfonamides - pharmacology
α-Melanocyte stimulating hormone
Prostaglandins
α-Melanocyte stimulating hormone
Nitric oxide
Endotoxemia
Neutrophils
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Summary:We investigated the effect of α-melanocyte stimulating hormone (α-MSH) on endotoxin-induced intestinal inflammation and the role of nitric oxide and prostaglandins in this response. α-MSH treatment (25 μg/rat, intraperitoneally (i.p.); twice daily) reduced the severity of the lesions macroscopically and microscopically. This protective effect was found to be confined mainly to the distal ileum. These lesions were reversed by pretreatment with the non-selective COX inhibitor indomethacin (10 mg/kg, subcutaneously (s.c.)) but not by the selective COX-2 inhibitor nimesulide (3 mg/kg, s.c.), the NO donor sodium nitroprusside (4 mg/kg, i.v.) or the iNOS inhibitor dexamethasone (3 mg./kg, i.p.) at macroscopic level and reversed by Indo or Dex at microscopic level. Increased peroxidase activity -index of tissue neutrophil infiltration- in the distal ileum of LPS-treated rats was decreased by α-MSH and this effect was reversed by pretreatment with Indo. In conclusion, the neuropeptide α-MSH has a beneficial effect on endotoxin-induced distal intestinal lesions by a mechanism which probably involves nitric oxide and COX-1 derived prostaglandins.
ISSN:0196-9781
1873-5169
DOI:10.1016/S0196-9781(01)00551-4