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Azelnidipine Ameliorates Dementia in Streptozotocin Treated Rats: Interplay between Oxidative Stress and Calcium

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Abstract

Deregulation of brain Ca2+ homeostasis is linked with oxidative stress, mitochondrial dysfunction, neurodegeneration, loss of synaptic plasticity, and cholinergic deficits. Earlier chronic administration of calcium channel blockers (L-type CCBs) has afforded relief in Alzheimer’s disease (AD) symptoms. Azelnidipine (AZL) is a long duration L-type Ca2+ channel blocker recently included in anti-hypertensive therapy. The present study reveals the role of AZL in the management of ICV-STZ induced AD in rats. Wistar rats of either sex (aged 12–15 weeks and weight range 260–280 g) were divided into 6 groups in single blind fashion and stereotaxic surgery was performed. Streptozotocin (3 mg/kg) was injected (ICV) in five groups and one group was administered with ACSF. AZL was administered (1.5, 3 and 6 mg/kg; p.o.) to separate groups of ICV-STZ pre-treated rats for 14 successive days. Memory of rats was measured using elevated plus maze and novel object recognition task. After behavioral evaluation, the animals were sacrificed and whole brains were isolated for estimation of AChE activity, TBARS and GSH levels. ICV-STZ treatment increased the brain AChE activity, TBARS level, decreased GSH level, and thereby impaired the memory of rats. The Ca2+ antagonistic property of AZL attenuated the STZ induced derangement of biochemical parameters and resurrected the memory functions in rats. This study exhibited that long-term blockade of the L-type Ca2+ channels using azelnidipine mitigates AD type dementia owing to its neuroprotective and antioxidant properties.

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ACKNOWLEDGMENTS

The authors are thankful to the A.S.B.A.S.J.S.M. College of Pharmacy, (Ropar) for providing the necessary research facility.

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Authors and Affiliations

  1. Department of Pharmacology, A.S.B.A.S.J.S.M. College of Pharmacy, 140111, Bela, Ropar, India

    Pardeep Singh, Manish Kumar & Nitin Bansal

  2. I.K. Gujral Punjab Technical University, Kapurthala, Punjab, India

    Manish Kumar

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  1. Pardeep Singh
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Correspondence to Nitin Bansal.

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Ethical approval. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Pardeep Singh, Kumar, M. & Bansal, N. Azelnidipine Ameliorates Dementia in Streptozotocin Treated Rats: Interplay between Oxidative Stress and Calcium. Neurochem. J. 13, 274–282 (2019). https://doi.org/10.1134/S1819712419030139

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