Regulation of arginase/nitric oxide synthesis axis via cytokine  balance contributes to the healing action of malabaricone B against  indomethacin-induced gastric ulceration in mice.
The role of the arginine-metabolism in the healing action of the Myristica malabarica phenol malabaricone B (mal B) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg kg- 1) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (30.8%, P < 0.01), eNOS expression, along with increased iNOS expression, total NOS activity (5.55 folds, P < 0.001), NO generation (2.19 folds, P < 0.001), and ratio of pro-/anti-inflammatory cytokines. Besides providing comparable healing as omeprazole (3 mg kg- 1 x 3 days), mal B (10 mg kg- 1 x 3 days, p. o.) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (51.6%, P < 0.001), eNOS expression, and reduced iNOS expression, total NOS activity (approximately 75%, P < 0.001), and NO level (50.6%, P < 0.01). These could be attributed to a favourable anti/pro inflammatory cytokines ratio, generated by mal B. The healing by omeprazole was however, not significantly associated with those parameters.
Maity
Biswanath
B
Department of Biochemistry, Dr BC Roy Post Graduate Institute of Basic Medical Sciences & IPGME&R, Kolkata, India.
Banerjee
Debashish
D
Bandyopadhyay
Sandip Kumar
SK
Chattopadhyay
Subrata
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D001119:Arginase / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D009853:Omeprazole / Q000627:therapeutic use*; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012118:Resorcinols / Q000737:chemistry / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D016207:Cytokines; D012118:Resorcinols; D009569:Nitric Oxide; C071788:malabaricone B; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D001119:Arginase; D009853:Omeprazole; D007213:Indomethacin