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Published in: Metabolic Brain Disease 1/2018

01-02-2018 | Original Article

Long-term treatment of diabetic rats with vanadyl sulfate or insulin attenuate acute focal cerebral ischemia/reperfusion injury via their antiglycemic effect

Authors: Hossein Ahmadi-Eslamloo, Gholam Abbas Dehghani, Seyed Mostafa Shid Moosavi

Published in: Metabolic Brain Disease | Issue 1/2018

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Abstract

It is well-known that patients with diabetes mellitus have worse clinical outcomes following acute ischemic stroke. The intensifying effects of diabetes on ischemic brain injury have been shown to be mostly due to hyperglycemia, rather than the lack of insulin direct effects on brain. It is also well-approved that vanadium compounds have insulin-like and anti-diabetic effects, and the present study was designed to compare the protective effects of diabetes treatment with vanadium or insulin on ischemic/reperfused brain injury. Male Sprague-Dawley rats were divided into 4 groups (n = 21). Two groups of streptozotocin-induced diabetic rats were treated with either vanadyl sulfate or insulin at proper doses to similarly attenuate hyperglycemia during 45 days, while there was no treatment in the control diabetic and non-diabetic sham groups. Thereafter, all treated and non-treated diabetic rats were subjected to 60-min of the right middle cerebral artery occlusion followed by 12-h reperfusion, and then their brains were removed for evaluating blood-brain barrier leakage, tissue swelling, infarct size and oxidant status in both hemispheres. Vanadium and insulin that equally reduced blood glucose and water intake had some differences in their antidiabetic effects of ameliorating weight loss and hypertension during 45-days treatment period. However, they caused similar decrements in levels of Evans blue dye extravastion, edema, infarct volume and malondialdehyde in ischemic/reperfused cerebral hemisphere. Therefore, it can be suggested that insulin and vanadium via their antiglycemic effect cause reduction in cerebral production of oxidants following acute focal ischemia/reperfusion, which attenuate BBB disruption and brain tissue injury.
Literature
go back to reference Ahmadi-Eslamloo H, Moosavi SM, Dehghani GA (2017) Cerebral ischemia-reperfusion injuries in vanadyl-treated diabetic rats. Iran J Med Sci 42(6):544–552 Ahmadi-Eslamloo H, Moosavi SM, Dehghani GA (2017) Cerebral ischemia-reperfusion injuries in vanadyl-treated diabetic rats. Iran J Med Sci 42(6):544–552
go back to reference Cam MC, Brownsey RW, McNeill JH (2000) Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 7:829–847CrossRef Cam MC, Brownsey RW, McNeill JH (2000) Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent? Can J Physiol Pharmacol 7:829–847CrossRef
go back to reference Dehghani GA, Ahmadi S, Omrani GR (1997) Effects of vanadyl sulphate on glucose homeostasis in severe diabetes induced by streptozotocin in rats. Indian J Med Res 106:481–485PubMed Dehghani GA, Ahmadi S, Omrani GR (1997) Effects of vanadyl sulphate on glucose homeostasis in severe diabetes induced by streptozotocin in rats. Indian J Med Res 106:481–485PubMed
go back to reference Hasegawa Y, Morioka M, Hasegawa S, Matsumoto J, Kawano T, Kai Y, Yano S, Fukunaga K, Kuratsu J (2006) Therapeutic time window and dose dependence of neuroprotective effects of sodium orthovanadate following transient middle cerebral artery occlusion in rats. J Pharmacol Exp Ther 317(2):875–881. https://doi.org/10.1124/jpet.105.096677 CrossRefPubMed Hasegawa Y, Morioka M, Hasegawa S, Matsumoto J, Kawano T, Kai Y, Yano S, Fukunaga K, Kuratsu J (2006) Therapeutic time window and dose dependence of neuroprotective effects of sodium orthovanadate following transient middle cerebral artery occlusion in rats. J Pharmacol Exp Ther 317(2):875–881. https://​doi.​org/​10.​1124/​jpet.​105.​096677 CrossRefPubMed
go back to reference Keshavarz S, Dehghani GA (2017) Cerebral ischemia/reperfusion injury in the hyperthyroid rat. Iran J Med Sci 42(1):48–56PubMedPubMedCentral Keshavarz S, Dehghani GA (2017) Cerebral ischemia/reperfusion injury in the hyperthyroid rat. Iran J Med Sci 42(1):48–56PubMedPubMedCentral
go back to reference Li L, Gao L, Liu S, Liu Q, Sun S, Huan Y, Li C, Peng J, Hou G, Li L, Liu W, Shen Z (2013) Bis(α-furancarboxylato)oxovanadium(IV) exerts durable antidiabetic effects and suppresses matrix metalloproteinase-2 activity in spontaneous type 2 diabetic KKAy mice. Biol Trace Elem Res 153(1-3):329–339. https://doi.org/10.1007/s12011-013-9689-5 CrossRefPubMed Li L, Gao L, Liu S, Liu Q, Sun S, Huan Y, Li C, Peng J, Hou G, Li L, Liu W, Shen Z (2013) Bis(α-furancarboxylato)oxovanadium(IV) exerts durable antidiabetic effects and suppresses matrix metalloproteinase-2 activity in spontaneous type 2 diabetic KKAy mice. Biol Trace Elem Res 153(1-3):329–339. https://​doi.​org/​10.​1007/​s12011-013-9689-5 CrossRefPubMed
go back to reference Mohammadi MT, Shid Moosavi SM, Dehghani GA (2011) Contribution of nitric oxide synthase (NOS) activity in blood-brain barrier disruption and edema after acute ischemia/reperfusion in aortic coarctation-induced hypertensive rats. Iran Biomed J 15(1-2):22–30PubMedPubMedCentral Mohammadi MT, Shid Moosavi SM, Dehghani GA (2011) Contribution of nitric oxide synthase (NOS) activity in blood-brain barrier disruption and edema after acute ischemia/reperfusion in aortic coarctation-induced hypertensive rats. Iran Biomed J 15(1-2):22–30PubMedPubMedCentral
go back to reference Niu X, Xiao R, Wang N, Wang Z, Zhang Y, Xia Q, Yang X (2016) The molecular mechanisms and rational design of anti-diabetic vanadium compounds. Curr Top Med Chem 16(8):811–822CrossRefPubMed Niu X, Xiao R, Wang N, Wang Z, Zhang Y, Xia Q, Yang X (2016) The molecular mechanisms and rational design of anti-diabetic vanadium compounds. Curr Top Med Chem 16(8):811–822CrossRefPubMed
go back to reference Ozkul A, Ayhan M, Akyol A, Turgut ET, Kadikoylu G, Yenisey C (2013) The effect of insulin resistance on inflammatory response and oxidative stress in acute cerebral ischemia. Neuroendocrinol Lett 34(1):52–57PubMed Ozkul A, Ayhan M, Akyol A, Turgut ET, Kadikoylu G, Yenisey C (2013) The effect of insulin resistance on inflammatory response and oxidative stress in acute cerebral ischemia. Neuroendocrinol Lett 34(1):52–57PubMed
go back to reference Soveid M, Dehghani GA, Omrani GR (2013) Long- term efficacy and safety of vanadium in the treatment of type 1 diabetes. Arch Iran Med 16(7):408–411. 10.13167/AIM.009 PubMed Soveid M, Dehghani GA, Omrani GR (2013) Long- term efficacy and safety of vanadium in the treatment of type 1 diabetes. Arch Iran Med 16(7):408–411. 10.​13167/​AIM.​009 PubMed
go back to reference Vakili A, Nekooeian AA, Dehghani GA (2004) L-NAME and 7-nitroindazole reduces brain injuries in transient focal cerebral ischemia in rat. Iran J Med Sci 29:109–115 Vakili A, Nekooeian AA, Dehghani GA (2004) L-NAME and 7-nitroindazole reduces brain injuries in transient focal cerebral ischemia in rat. Iran J Med Sci 29:109–115
Metadata
Title
Long-term treatment of diabetic rats with vanadyl sulfate or insulin attenuate acute focal cerebral ischemia/reperfusion injury via their antiglycemic effect
Authors
Hossein Ahmadi-Eslamloo
Gholam Abbas Dehghani
Seyed Mostafa Shid Moosavi
Publication date
01-02-2018
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 1/2018
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-017-0153-7

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