Melatonin (MT) is an ubiquitous molecule, representing one of the phylogenetically oldest signaling mechanisms. Our previous studies demonstrated that MT and its precursor
L-tryptophan (L-Trp) show strong protective effect on gastric mucosa. The aim of the present study was: 1) to assess the effect of MT and L-Trp on healing of chronic
gastric ulcer and accompanying changes in gastric mucosal blood flow (GBF); 2) to study the effect of MT and L-Trp on expression of iNOS. cNOS and HSP70 in ulcerated mucosa; 3) to compare the effect of L-Trp free and L-Trp rich diet on
ulcer healing and gene expression of proinflammatory
cytokines such as
tumor necrosis factor-alpha (
TNF-alpha),
superoxide dismutase (SOD),
cyclooxygenase-2 (COX-2) and NFkappaB-p65
protein expression in
ulcer area and intact non-ulcerated. Chronic
ulcers were induced in Wistar rats by Okabe's modification of
acetic acid method. Rats with chronic
gastric ulcers were divided in following treatment groups: 1) vehicle (saline); 2) MT (20mg/kg-d i.p.) and 3) L-Trp (100 mg/kg i.p.). The expression of iNOS, cNOS and HSP70
protein was measured by Western blot. In separate experiments, the influence of commercially available (Bio-Serv, USA) L-Trp free diet (TFD) was compared to the L-Trp rich diet (TRD) on the course of
ulcer healing was assessed. The
ulcer area was measured by planimetry. The expression of
TNFalpha, COX-2 and SOD
mRNA in ulcerated mucosa was analyzed by RT-PCR method. MT and its precursor L-Trp significantly accelerated
ulcer healing. Healing ulcerated mucosa showed increased
protein expression of iNOS and HSP70 as compared to intact gastric mucosa. TFD in contrast to normal diet significantly attenuated the
ulcer healing, whereas the TRD exerted opposite effects and significantly accelerated
ulcer healing. This last effect was accompanied by significant decrease of
TNF-alpha mRNA expression and expression of NFkB-p65 in gastric mucosa. We conclude that: 1) MT and its precursor L-Trp significantly accelerate healing of
gastric ulcer; 2) L-Trp free diet significantly attenuates experimental
ulcer healing and this is due to decreased synthesis of MT from L-Trp by EE cells in gastric mucosa and 3) MT shows strong anti-inflammatory effects due to inhibition of NFkappaB and
TNF-alpha expression.