Gastroprotection induced by silymarin, the hepatoprotective principle of Silybum marianum in ischemia-reperfusion mucosal injury: role of neutrophils.
Investigations were carried out to determine the antiulcer effects of silymarin, the hepatoprotective principle of Silybum marianum L. Gaertn., in gastric injury induced by ischemia-reperfusion and its effects on mucosal myeloperoxidase activity, an index of polymorphonuclear leukocyte infiltration, after injury in rats. These results were compared with those from rats that received allopurinol, an inhibitor of xanthine oxidase and with those from rats made neutropenic by prior administration of dexamethasone and methotrexate. Pretreatment with silymarin prevented post-ischemic mucosal injury. The mean ulcer indexes (U.I.) of rats treated with 25, 50 mg, and 100 mg silymarin/kg body weight (4.79 +/- 0.75, 4.50 +/- 0.81, and 3.63 +/- 0.74, respectively) were significantly lower (p < 0.05, 0.05, and p < 0.005) than that of control rats. Allopurinol was considerably more potent in reducing the U.I. than silymarin, with a calculated U.I. of 2.33 +/- 0.45, p < 0.001. These protective effects were specifically related to a reduction in the number of neutrophils in the gastric mucosa. Reduction in the numbers of circulating neutrophils by treating rats with methotrexate (MPO level of 7.2 x 10(-2) +/- 0.56 x 10(-2)U/mg wt) and dexamethasone (MPO level of 6.97 x 10(-2) +/- 0.68 x 10(-2)U/mg wt) also resulted in a significant reduction in the susceptibility to gastric damage induced by ischemia-reperfusion. These results suggest that neutrophils play an important role in the gastric mucosal dysfunction associated with ischemia-reperfusion. These findings also indicate that the inhibitory effects of silymarin on neutrophil function may contribute significantly to its gastroprotective actions.
Alarcón de la Lastra
A C
AC
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Sevilla, Spain.
Martín
M J
MJ
Motilva
V
V
Jiménez
M
M
La Casa
C
C
López
A
A
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010944:Plants / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D012838:Silymarin / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000150:complications / Q000517:prevention & control*
D000897:Anti-Ulcer Agents; D012838:Silymarin; D009195:Peroxidase