[ effects of genistein, a tyrosine kinase inhibitor, on acute and chronic inflammation in diabetic mice]

ABSTRACT

The effects of tyrosine kinases on acute and chronic inflammation during diabetes are not fully determined. Therefore, the present study focuses on investigating the effects of genistein, a tyrosine kinase inhibitor, on acute and chronic inflammation in diabetic mice. The mice either received normal saline [control, 0.1 ml, i.p., n=144] or were injected with streptozotocin [diabetic, STZ, 200 mg kg -1, i.p., n=144]. By injecting carrageenan and implanting 2 cotton pellets [a week after the injection of saline or STZ] we induced acute and chronic inflammation. Before injecting carrageenan or 5 day after implantation, 9 mice from each group [control or diabetic] received genistein [10 mg kg -1, i.p.], indomethacin [2 mg kg -1, i.p.] or L-NAME [0.1 mg kg -1, i.p.]. Paw edema and the weight of cotton pellets were significantly higher in diabetic mice. Pretreatment with either indomethacin or L NAME significantly reduced the acute and chronic inflammation in the diabetic group. Genistein reduced chronic inflammation significantly [P<0.0001]. These results suggest that activation of tyrosine kinases as well as prostaglandins and nitric oxide pathways are involved in the increased chronic inflammatory responses observed in the diabetic animals