Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions

Abstract

Ischemia/reperfusion injury (IRI) during kidney transplantation is a serious clinical problem with a high mortality rate and a lack of therapy. Therefore, there is a need to improve the ability of the kidney to tolerate IRI during transplantation. This study aimed to investigate the possible protective effect of vinpocetine; a derivative of vincamine alkaloid; against renal IRI in rats with the elucidation of the involved mechanisms. Vinpocetine (25 mg/kg; i.p.) was administered for 10 successive days before the induction of ischemia by bilateral clamping of both renal pedicles for 45 min followed by 24 h of reperfusion. Blood and renal tissue samples were then collected for biochemical, molecular, and histopathological investigations. Vinpocetine significantly reduced serum creatinine and blood urea nitrogen levels in rats subjected to IRI. It also reduced mRNA expression of NADPH oxidase and renal content of malondialdehyde, while enhanced Nrf2 protein expression and renal content of reduced glutathione. The suppression of the provoked inflammatory response was evident by the downregulation of IKKβ and NF‐κB p65 protein expressions, as well as their downstream inflammatory markers; tumor necrosis factor‐α, interleukin‐6, and myeloperoxidase. In addition, vinpocetine reduced protein expression of the apoptotic executioner cleaved caspase‐3. These nephroprotective effects were confirmed by the improvement in histopathological features. Collectively, the protective effect of vinpocetine against IRI could be attributed to modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions. Thus, vinpocetine could improve oxidant/antioxidant balance, suppress triggered inflammatory response, and promote renal cell survival after IRI.

Effect of vinpocetine against acrylamide‐induced nephrotoxicity in rats

“…Vinpocetine has an antiapoptotic impact on renal Ischemia/reperfusion injury (IRI), which may be caused either directly by inhibiting activated caspase‐3 or indirectly through its antioxidant and anti‐inflammatory activities. [ 34 ] Expression levels of caspase‐3 and Bcl‐2 in cisplatin‐induced AKI rats decreased after administration of VIN (5 mg/kg, p.o.) for 10 days.…”

The anti-inflammatory properties of vinpocetine mediates its therapeutic potential in management of atherosclerosis

“…Besides, protective effect of VPN against ischemic reperfusion injury (IRI) could be attributed to inhibtion of NADPH oxidase/Nrf2, IKKβ/NF-κB p65, and cleaved caspase-3 expressions. Thus, VPN could improve oxidant/antioxidant balance, suppress inflammatory response, and promote cell survival after IRI [ 46 ]. These verdicts suggest that VPN may be effective against the development of inflammatory disorders in AS by suppressing of inflammatory reactions.…”

Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

“… 61 VNP additionally restores renal function, boosts antioxidant defence, and attenuates inflammation after ischaemic reperfusion injury. 62 , 63…”