Rp. Korolkiewicz et al., Polaprezine exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats, DIG DIS SCI, 45(6), 2000, pp. 1200-1209
We examined the influence of diabetes mellitus (DM) on the healing of HCl-i
nduced gastric lesions and the healing promoting effect of polaprezinc [N-(
3-aminopropionyl)-6-histiclinnto zinc] on these lesions. Studies were perfo
rmed on rats injected intraperitoneally with streptozotocin (STZ, 70 mg/kg)
five weeks prior to experiments. Diabetic rats had blood glucose levels (B
GLs) higher than 350 mg/100 ml. Randomly chosen animals were treated subcut
aneously with insulin (4 IU/day/rat) starting 1 week after STZ. Animals wer
e given 1 ml of 0.6 N HCl by oral gavage (per os) following 18 hr of fastin
g; they were fed normally from 1 hr later and killed at various lime points
after HCl administration. Polaprezinc (3-30 mg/kg) or its components ZnSO4
/7H(2)O and L-carnosine were given orally, twice daily fur four days follow
ing HCl treatment. Gastric lesions induced by HCl healed macroscopically to
quiescence within 10 days. DM and insulin did not affect the development o
f HCl-invoked gastric lesions, but the healing of such lesions was markedly
impaired in animals with DM. Daily administration of insulin returned high
BGLs to significantly lower ranges (190-208 mg/100 ml) and markedly antago
nized the healing impairment. Polaprezinc (> 10 mg/kg) significantly revers
ed the delay observed in diabetic rats without any notable effects on BGLs
or acid secretion, Similar trends were observed with 1 ZnSO4/7H(2)O or a mi
xture of ZnSQ4/7H(2)O and L-carnosine, but not by L-carnosine alone. The mu
cosal expression of insulin-like growth factor-1 (IGF-I) mRNA was significa
ntly lower in diabetic rats, a dysregulation partially corrected by insulin
and polaprezinc. In addition, the delayed healing in diabetic rats was als
o significantly promoted by the repeated subcutaneous administration of rhI
GF-I (> 10 mu g/kg, twice daily) without any notable effect on BGLs or acid
secretion. These results suggest that DM exerted a deleterious influence o
n the healing of acute gastric lesions in both insulin- and zinc-sensitive
manner. The salutary effects of polaprezinc on the impaired healing of gast
ric lesion in STZ-diabetic animals may at least be partly explained by enha
ncement of mucosal IGF-I mRNA expression in the stomach.