Neuroprotective potentials of candesartan, atorvastatin and their combination against stroke induced motor dysfunction

Abstract

Cerebral ischaemia is a leading cause of death and disability. The objective of the present investigation was to explore the neuroprotective potentials of candesartan and atorvastatin alone and their combination against the cerebral ischaemia induced behavioral, biochemical, and mitochondrial dysfunction. Male Wistar rats (200-220 g) were subjected to bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion. Candesartan (0.1 and 0.3 mg/kg) and atorvastatin (10 and 20 mg/kg) were pretreated for 7 days before animals were subjected to ischaemia reperfusion injury. Various behavioral tests (locomotor activity and rotarod performance), biochemical parameters (Malondialdehyde levels, nitrite concentration, superoxide dismutase and catalase activity, redox ratio, and GST) and mitochondrial enzyme (Complex I, II, III, and IV) dysfunctions were measured in cerebral cortex, striatum and hippocampus of the ischaemic brain. Seven days candesartan (0.1 and 0.3 mg/kg) or atorvastatin (10 and 20 mg/kg) pretreatment significantly attenuated neurobehavioral alterations, oxidative damage and restored mitochondrial enzyme dysfunction as compared to control (I/R) group. Further, combined treatment of candesartan (0.1 mg/kg) and atorvastatin (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone. Present study suggests the protective effect of candesartan and atorvastatin and their combination against ischaemia reperfusion induced behavioral and biochemical alterations in rats.

Statins enhance cognitive performance in object location test in albino Swiss mice: Involvement of beta-adrenoceptors

“…In accordance to this, Ludka et al demonstrated that a single administration of atorvastatin in a range dose of 0.01 to 30 mg/kg, did not cause any changes in locomotor parameters [40]. It has been shown that 1 week of atorvastatin treatment (10 and 20 mg/kg) improved the deficit promoted by stroke in the locomotors patterns, but atorvastatin per se did not cause any changes in OF [41]. The literature demonstrates that 2 weeks of simvastatin treatment do not change exploratory patterns in open field in rats, however 4 weeks of simvastatin (10 mg/kg) treatment promotes an increase in distance traveled in the open field task [14,19].…”

Candesartan and epigallocatechin‐3‐gallate ameliorate gentamicin‐induced renal damage in rats through p38‐MAPK and NF‐κB pathways

“…Either candesartan or EGCG exhibited potent antioxidant activity and decreased gentamicin‐induced nephrotoxicity, which was verified by restoring the oxidative balance. There are different experimental studies which demonstrated their antioxidant effects …”

“…There are different experimental studies which demonstrated their antioxidant effects. [38,[41][42][43][44] Inflammatory progression induced by gentamicin was evident also by the notable elevation in renal levels of key inflammatory cytokines;…”

Amelioration of Stroke-Induced Neurological Deficiency by Lyophilized Powder of Catapol and Puerarin

“…As in the case of rt-PA in combination with aspirin, it is a common and effective treatment against stroke in clinical now. Besides, Candesartan with atorvastatin 38, Memantine with Clenbuterol 39 and Vitamin Dhormone (VDH) with progesterone (P4) can protect brain from stroke 40. Beyond the combination in clinical drugs, drug with peptid can treat acute stroke better as well 41.…”