Effects of rutin and harmaline on rat reflux oesophagitis.
1. This study was aimed at evaluating the effect of rutin and harmaline (1-methyl-7-methoxy-3,4-dihydro-beta-carboline) on the development of the surgically induced reflux oesophagitis, on gastric secretion, lipid peroxidation, polymorphonucleocytes (PMNs) accumulation, superoxide and hydroxyl radical production in PMNs, cytokine [interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha)] production in blood and [Ca2+]i mobilization in PMNs. 2. Rutin and harmaline significantly prevented the development of reflux oesophagitis and gastric secretion. Treatments of oesophagitis rats with rutin and harmaline inhibited lipid peroxidation, and myeloperoxidase (MPO) in the oesophagus in comparison with untreated rats. 3. Superoxide anion and hydrogen peroxide production in 1 microm formylmethionylleucylphenylalanine (fMLP)- or 0.1 microg ml-1N-phorbol 12-myristate 13-acetate (PMA)-activated PMNs was inhibited by rutin and harmaline in a dose-dependent fashion. Rutin and harmaline effectively scavenged the hydroxyl radical and hydrogen peroxide. Treatments of oesophagitis rats with rutin and harmaline inhibited IL-1beta production in the oesophagus in comparison with untreated rats, but TNF-alpha production was not affected by rutin and harmaline. The fMLP-induced elevation of [Ca2+]i was inhibited by rutin. 4. The results of this study suggest that rutin and harmaline may have beneficial protective effects against reflux oesophagitis by the inhibition of gastric acid secretion, oxidative stress, inflammatory cytokine production (i.e. IL-1beta), and intracellular calcium mobilization in PMNs in rats.
Shin
Y K
YK
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea.
Sohn
U D
UD
Choi
M S
MS
Kum
C
C
Sim
S S
SS
Lee
M Y
MY
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004942:Esophagitis, Peptic / Q000378:metabolism / Q000517:prevention & control*; D004947:Esophagus / Q000201:enzymology; D005744:Gastric Acid / Q000378:metabolism; D006246:Harmaline / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009195:Peroxidase / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*
D016207:Cytokines; D012431:Rutin; D006246:Harmaline; D009195:Peroxidase