Abstract 53: Telmisartan But Not Tempol Improves the Already Established Renal Cell Senescence in Type 2 Diabetic Rats
We previously reported that hyperglycemia induces renal tubular cell senescence in type 1 diabetic animals. In the present study, we evaluated the tubular cell senescence in type 2 diabetic animals and investigated whether the renal cell senescence could regress in response to treatment with a reno-protective dosage of an angiotensin receptor blocker, telmisartan (10 mg/kg/day). Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneously developed type 2 diabetes, showed an age-dependent increase in renal cell senescence analyzed by p21 expression (6 weeks old: 1.3±0.3 fold, 22 weeks old: 2.6±0.3 fold, vs. age-matched lean control rats, n=8, respectively) and senescence-associated β galactosidase (SABG) staining. OLETF rats were separated into the following 3 groups at 22 weeks of age and were kept under treatment until 34 weeks of age (n=10 per group): 1) un-treated, 2) telmisartan, and 3) tempol (an anti-oxidant, 3 mmol/L in drinking water). Neither treatment affected the blood glucose levels. Telmisartan, but not tempol, markedly reduced SABG staining by 34 weeks of age compared with that at 22 weeks of age or with that of age-matched un-treated rats. Increase in the expression of p21 was significantly smaller in telmisartan-treated rats (1.3±0.2 fold vs. lean rats) than in un-treated rats (2.9±0.2 fold, p<0.01) and tempol-treated rats (3.0±0.2 fold, p<0.01). Un-treated OLETF rats showed a greater intrarenal expression of TNF-α than lean rats, and the increase was suppressed by telmisartan. On the other hand, ED-1-positive macrophages rarely colocalized with p21-positive tubules at any stage of diabetes in any treated groups. These results indicate that type 2 diabetes prompts the renal cell senescence and that accumulation of renal senescent cells is reversible. Macrophage infiltration seems unlikely to contribute to the reduction of senescent cells. In addition, while there are many reports showing the involvement of oxidative stress in cell senescence, anti-oxidant tempol did not affect the established cell senescence.
- © 2012 by American Heart Association, Inc.