Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats.
Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water-maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-γ agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia.
CNS and CVS Lab, Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass Meerut, Pin-250103, Uttar Pradesh, India. Electronic address: sharmaslab6@gmail.com.
Swati
S
Jain
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, A-Block, Ground Floor, Sector-125, Noida 201303, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India. Electronic address: drbhupeshresearch@gmail.com.
Bhupesh
B
Sharma
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003704:Dementia / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010180:Pancreatectomy / Q000009:adverse effects; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012430:Ruthenium Red / Q000627:therapeutic use*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D009566:Nitrates; D009573:Nitrites; D019837:Ryanodine Receptor Calcium Release Channel; D045162:Thiazolidinediones; D012430:Ruthenium Red; D000077205:Pioglitazone
Attentional-set shifting; Blood brain barrier; Inflammation; Morris water maze; Oxidative stress; Ryanodine receptor antagonist