Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

Abstract

Studies have shown that tetracycline class antibiotics exhibit an ameliorating action with its antioxidant property on increased oxidative stress in tissues, including heart. Since endothelial vascular dysfunction in diabetes is associated with increased oxidative stress and prevented with antioxidants, herein, we aimed to test a hypothesis whether a low-dose doxycycline treatment of diabetic rats for 4 weeks can ameliorate endothelial vascular dysfunction of thoracic aortas. Results of the present study shows that both direct and alpha receptor-mediated contractile responses as well as endothelium-dependent and endothelium-independent vasodilatory responses were preserved with low-dose doxycycline treatment (30 μmol/kg, daily; for 4 weeks) compared with untreated diabetic group. Furthermore, doxycycline treatment normalized increased lipid peroxidation and cellular glutathione level measured in plasma and prevented diabetes-induced impaired body weight gain without significant effect on high blood glucose level. Increased membrane protein level of caveolin-1, elevated ratio of PKC in particulate and cytosolic fraction, and increased protein level of cytosolic endothelin-1 in diabetic rats were also significantly prevented with doxycycline treatment. Moreover, diabetes-induced another type of oxidative stress markers in rats, matrix metalloproteinases, MMP-2, and MMP-9 were also normalized with doxycycline treatment in blood. Taken together, our data address that amelioration and/or prevention of vascular endothelial and contractile dysfunction by doxycycline is accompanied by a clear reduction in oxidative stress markers of diabetes, which provides evidence for doxycycline's potential antioxidant action as a therapeutic agent for amelioration and/or prevention of vascular disorders in diabetic subjects.

Enhancement of Cellular Antioxidant-Defence Preserves Diastolic Dysfunction via Regulation of Both Diastolic Zn2+and Ca2+and Prevention of RyR2-Leak in Hyperglycemic Cardiomyocytes

“…Furthermore, total protein-thiol level was not affected by either diabetes or NAC treatment (data not shown). We, therefore, demonstrated that there is marked increase in oxidative stress in the heart of diabetics besides a high circulatory level of lipid peroxidation [32] from STZ-induced diabetic rat, and it can be controlled to normal level by NAC treatment, which is confirmed also with previously published data [33–35]. …”

Protective effect of sitagliptin and rosuvastatin combination on vascular endothelial dysfunction in type-2 diabetes

“…Acetylcholine (ACh) and sodium nitroprusside-induced vasorelaxation were studied on isolated rat aortas. Oxidative stress indices such as SOD, CAT, LPO and NO levels were determined in rat aortas at end of the treatments[1617]. …”

Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention

“…This was attributed to an inhibition of eNOS function due to cav-1 binding and a reduction of NO production [189, 190]. …”