Reduction of circulating superoxide dismutase activity in type 2 diabetic patients with microalbuminuria and its modulation by telmisartan therapy

Abstract

Growing evidence indicates that oxidative stress induced by excessive superoxide has a central role in the pathogenesis of diabetic nephropathy (DN). Telmisartan, one of the currently available angiotensin II type 1 receptor blockers (ARBs), has been shown to exert a more powerful proteinuria (albuminuria) reduction in patients with DN, but whether the prominent renoprotective effect of telmisartan is mediated through enhancing antioxidant defense capacity and reducing oxidative stress has not been fully elucidated. The present study first revealed that the serum activity of superoxide dismutase (SOD) responsible for superoxide removal is reduced in the DN stage of microalbuminuria, but not in normoalbuminuria in type 2 diabetic patients. We next examined the alteration of SOD and oxidative stress following an 8-week treatment with telmisartan (40 mg per day) in 12 type 2 diabetic patients with microalbuminuria. Interestingly, the telmisartan treatment not only reduced the circulating levels of two oxidative stress markers, 8-hydroxy-2¢-deoxyguanosine (8-OHdG) and nitrotyrosine (NT), but also enhanced serum SOD activity. Notably, a significant correlation was observed between the increase in serum SOD activity and the reduction in albuminuria. We further compared the anti-oxidative effect of telmisartan with that of losartan, another member of the ARB class, by implementing an 8-week interval crossover treatment with these ARBs in another 12 microalbuminuric type 2 diabetic patients. The patients showed higher serum SOD activity, and lower circulating levels of 8-OHdG and NT, during treatment with telmisartan than with losartan. These results suggest that telmisartan has a more potent antioxidative effect through its ability to enhance SOD activity in type 2 diabetic patients with microalbuminuria.

DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria <i>via</i> up-regulation of SDF-1α in type 2 diabetic patients with incipient nephropathy

“…ARBs are widely used for the amelioration of proteinuria (albuminuria) in patients with DN, and provide more beneficial effects especially in incipient DN stage as shown in the INNOVATION study [31,32]. A large body of evidence from experimental studies and our clinical study suggests that ARBs exert greater anti-oxidative effects and ameliorate diabetic and oxidative renal injury [30,[33][34][35]. Moreover, a recent experimental study has reported that DPP-4 inhibition on top of angiotensin II type 1 receptor blockade provides more powerful renoprotective effects through highly reducing oxidative stress in diabetic kidney [4].…”

“…We have recently reported that renal oxidative stress is highly produced in the incipient DN stage, but not the normoalbuminuric stage, and that the incipient DN stage is more suitable than other stages for antioxidative intervention [30]. Treatment with DPP-4 inhibitors which have higher selectivity and stronger inhibitory activity for DPP-4 is expected to contribute greatly to the amelioration of renal oxidative stress and albuminuria in patients with incipient DN.…”

Therapeutic Insights against Oxidative Stress Induced Diabetic Nephropathy: A Review

“…A recent clinical study has shown it to be more effective in renoprotection as compared to other ARB class of drugs like losartan and valsartan owing to the difference in their intrinsic pharmacokinetic and physiochemical properties [160]. Furthermore, a number of properties like the best binding affinity to Ang II type 1 receptors, the maximum plasma halflife and the highest lipophilicity among the presently available…”

“…The effects of plant extracts on diabetic patients have shown to reduce the level of ROS, blood glucose level along with the improvement of antioxidants activity [113,191]. Studies on human also indicate the renal protective effect of above mentioned drugs by decreasing the expression of TGF-β and AGE, thereby preventing albuminuria [160,192]. But to increase the efficacy of above mentioned molecules, a targeted drug delivery system is essential and that is lacking in present scenario.…”

Albuminuria, serum antioxidant enzyme levels and markers of hemolysis and inflammation in steady state children with sickle cell anemia

“…The knowledge of the association of microalbuminuria with oxidative stress could be of therapeutic interest. Although the use of antioxidants and supplementation of enzyme cofactors can be conceivably envisaged, the prominent renoprotective effect of angiotensin II type 1 receptor blocker (ARB) Telmisartan in type 2 diabetes, a condition associated with microalbuminuria as SCA has been reported to be mediated through enhancing antioxidant defense capacity and reducing oxidative stress [6]. Unfortunately, data on oxidative stress in SCA patients with and without microalbuminuria are very scare in Africa, a setting where SCA is prevailing [7–10].…”