Objective: 

Oxidative stress may occur as a result of increased free – radical generation and/or to a decrease in antioxidant defense mechanism. For instance, in diabetes mellitus endothelium-dependent relaxation may be impaired by an excess generation of superoxide, which destroys nitric oxide. The aim of our research was to establish a possible relationship among peroxisome proliferator- activated receptor (PPAR) gamma agonist, b1 blockers, oxidative stress and endothelial dysfunction in diabetic animals.

Methods: 

Experiments were performed on adult male Wistar rats divided in five groups (n=10 / per group) as follows: group I: control group, group II: streptozotocin -induced diabetic rats, group III: diabetic rats treated with b1 blocker (Nevibolol), group IV: diabetic rats treated with PPAR gamma agonist (Pioglitazone) and group V: diabetic rats treated with PPAR gamma agonist and b1 blocker. Animals were sacrificed under ether anesthesia after 30 days and aortic segments and blood were taken in order to asses the oxidative stress markers (malondialdehyde, protein carbonyl groups), antioxidant defense (thyol groups, superoxide dismutase) and endothelial dysfunction (nitrates).

Results: 

There was a significant decrease (p< 0.001) in malondialdehyde levels due to both Nevibolol and Pioglitazone administration (0.6 ± 0.2 nmol/mg protein) compared to the diabetic animals (3.85 ± 1.8 nmol/mg protein), diabetic and Nevibolol treated animals (1.9 ± 0.5 nmol/mg protein), diabetic and Pioglitazone treated animals (1.4 ± 0.4 nmol/mg protein). A significant decrease (p< 0.001) in protein carbonyl groups levels in animals treated with both Nevibolol and Pioglitazone (1.6 ± 0.4 nmol/mg protein) was seen compared to the diabetic animals (9.3 ± 3.1 nmol/mg protein), diabetic and Nevibolol treated animals (4.1 ± 2.4 nmol/mg protein), diabetic and Pioglitazone treated animals (3.9 ± 1.6 nmol/mg protein). Blood antioxidant defense assessment revealed a significant increase (p< 0.001) in thyol groups levels in animals treated with both Nevibolol and Pioglitazone (4 ± 2.6 mmol/ml) as compared to the: diabetic animals (1.4± 0.3 mmol/ml), diabetic and Nevibolol treated animals (2.4 ± 1.2 mmol/ml), diabetic and Pioglitazone treated animals (2.8 ± 1.1 mmol/ml). Superoxide dismutase activities significantly increased (p<0.005) in animals treated with both Nevibolol and Pioglitazone (10.10 ± 3.6 U/mg protein) compared to the diabetic animals (4.66 ± 2.4 U/mg protein), diabetic and Nevibolol treated animals (7.8 ± 3.4 U/ mg protein), diabetic and Pioglitazone treated animals (8.3 ± 3.1 U/mg protein). Blood nitrates levels significantly increased (p< 0.001) in Nevibolol + Pioglitazone (0.6 ± 0.2 nmol/ml) treated animals compared to the: diabetic animals (0.1± 0.04 nmol/ml), diabetic and Nevibolol treated animals (0.2 ± 0.02 nmol/ml), diabetic and Pioglitazone treated animals (0.4 ± 0.1 nmol/ml).

Conclusions: 

Our findings suggested that PPAR gamma agonist and b1 blocker improved antioxidant defense decreased oxidative stress markers and normalized endothelium – dependent relaxation by increasing nitric oxide bioavailability via a reduction in the level of vascular reactive oxygen species.