Effects of allyl isothiocyanate from horseradish on several experimental gastric lesions in rats.
Allyl isothiocyanate is well known to be a principal pungent constituent of horseradish and an agonist for transient receptor potential (TRP) A1. Ally isothiocyanate markedly inhibited the formation of gastric lesions induced by ethanol (1.5 ml/rat, p.o.), 0.6 M HCl (1.5 ml/rat, p.o.), 1% ammonia (1.5 ml/rat, p.o.), and aspirin (150 mg/kg, p.o.) (ED(50)=1.6, 2.2, 1.7, ca. 6.5 mg/kg, p.o.). It also significantly inhibited the formation of gastric lesions induced by indomethacin (20 mg/kg, p.o.), though the inhibition was ca. 60% at a high dose (40 mg/kg, p.o.). Furthermore, several synthetic isothiocyanate compounds also significantly inhibited ethanol and indomethacin-induced gastric lesions. Whereas, TRPV1 agonists, capsaicin and piperine, inhibited gastric lesions induced by ethanol, 1% ammonia, and aspirin, but had less of an effect on 0.6 M HCl-induced gastric lesions. With regard to mode of action, the protective effects of ally isothiocyanate on ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin, but not with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), or ruthenium red. Pretreatment with indomethacin reduced the protective effects of piperine, and L-NAME reduced the effects of capsaicin and omeprazole. Furthermore, ruthenium red reduced the effects of capsaicin, piperine, and omeprazole. These findings suggest that endogenous prostaglandins play an important role in the protective effect of allyl isothiocyanate in ethanol-induced gastric lesions different from capsaicin, piperine, and omeprazole.
Matsuda
Hisashi
H
Department of Pharmacognosy, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Ochi
Momotaro
M
Nagatomo
Akifumi
A
Yoshikawa
Masayuki
M
D000470:Alkaloids / Q000494:pharmacology; D000641:Ammonia / Q000009:adverse effects; D000818:Animals; D031215:Armoracia / Q000737:chemistry; D001241:Aspirin / Q000009:adverse effects; D052117:Benzodioxoles / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005520:Food Preservatives / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006851:Hydrochloric Acid / Q000009:adverse effects; D007213:Indomethacin / Q000009:adverse effects; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009853:Omeprazole / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red; D013329:Structure-Activity Relationship
D000470:Alkaloids; D052117:Benzodioxoles; D005520:Food Preservatives; D017879:Isothiocyanates; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011453:Prostaglandins; D012430:Ruthenium Red; D000431:Ethanol; D000641:Ammonia; C004471:allyl isothiocyanate; D009853:Omeprazole; D006851:Hydrochloric Acid; D001241:Aspirin; D002211:Capsaicin; C008922:piperine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin