Azilsartan ameliorates aluminium chloride induced Alzheimer’s disease like pathology
Curr Issues Pharm Med Sci., Vol. 36, No. 3, 151-157
Sunita Mishra*, Shakti Ketan Prusty, Pratap Kumar Sahu, Debajyoti Das
School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, India
10.2478/cipms-2023-0026
© 2023 Author(s). This is an open access article distributed under the Creative Commons Attribution-NonComercial-No Derivs licence (http://creativecommons.org/licenses/by-nc-nd/3.0/)
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease manifested with accumulation of neurotoxic proteins like beta-amyloid (Aβ) and hyperphosphorylated tau. Administration of angiotensin receptor blockers (ARBs) such as Telmisartan has demonstrated to generate significant memory improvement in AD. Azilsartan is an ARB with better bioavailability than Telmisartan. Hence, the present work evaluates the efficacy of Azilsartan against aluminium chloride (AlCl3) induced AD. In the work, albino rats were divided into five groups (n=6). Group I served as control and received saline (10 ml/kg). Group-II was treated with AlCl3 (100 mg/kg) for 42 days; Group-III and IV received Azilsartan (5 mg/kg)
and Telmisartan (10 mg/kg) with AlCl3 daily for 42 days. Y-maze, elevated plus maze and radial arm maze were used to evaluate memory functions. This was followed by biochemical and histological studies, along-with determination of Aβ content and anti-oxidant status. AlCl3 was found to significantly (p <0.05) reduce cognition and increased concentration of Aβ in a hippocampus with elevated lipid peroxidation levels. It also significantly (p<0.05) decreased superoxide dismutase and increased malondialdehyde content. However, brain histology showed presence of neurofibrillary tangles, neuronal dead cells, and pyknotic cells compared to normal group. Still, Azilsartan and Telmisartan significantly (p<0.05) reversed cognitive dysfunction, improved antioxidant status and decreased Aβ production. Thus we conclude that Azilsartan protects AlCl3 induced AD-like pathology but, to a degree less than Telmisartan.
Full Text
Keywords
Alzheimer’s, memory, neuroprotective, amyloid-beta, AlCl3, angiotensin.
References
- Parihar MS, Hemnani T. Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci. 2004;11:456-67.
- Anand A, Patience AA, Sharma N, Khurana N. The present and future of pharmacotherapy of Alzheimer’s disease: A comprehensive review. Eur J Pharmacol. 2017;815:364-75.
- Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harbor Perspect Med. 2011;1:a006189.
- Sahu PK, Tiwari P, Prusty SK, Subudhi BB. Past and present drug development for alzheimer’s disease. In: Rahman A (Ed), Frontiers in clinical drug research – Alzheimer disorders, Vol 7. Bentham Science publishers. 2018, p. 214-253.
- Kawahara M, Kato-Negishi M. Link between aluminum and the pathogenesis of Alzheimer's disease: the integration of the aluminum and amyloid cascade hypotheses. Int J Alzheimer’s Dis. 2011;2011.
- L Blaylock R. Aluminum induced immunoexcitotoxicity in neurodevelopmental and neurodegenerative disorders. Curr Inorg Chem. 2012;2:46-53.
- Walton JR. A longitudinal study of rats chronically exposed to aluminum at human dietary levels. Neurosci Lett. 2007;412:29-33.
- Wu YH, Zhou ZM, Xiong YL, Wang YL, Sun JH, Liao HB, Luo XD. Effects of aluminum potassium sulfate on learning, memory, and cholinergic system in mice. Acta Pharmacol Sin. 1998;19:509-12.
- Platt B, Fiddler G, Riedel G, Henderson Z. Aluminium toxicity in the rat brain: histochemical and immunocytochemical evidence. Brain Res Bull. 2001;55:257-67.
- Shishido H, Kishimoto Y, Kawai N, Toyota Y, Ueno M, Kubota T, Kirino Y, Tamiya T. Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer’s disease. Neurosci Lett. 2016;629:62-67.
- Atlas SA. The renin-angiotensin aldosterone system: pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13:9-20.
- Ciobica A, Bild W, Hritcu L, Haulica I. Brain renin-angiotensin system in cognitive function: pre-clinical findings and implications for prevention and treatment of dementia. Acta Neurol Bel. 2009;109:171-80.
- Horiuchi M, Mogi M. Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage. Br J Pharmacol. 2011;163:1122-30.
- Sharma B, Singh N. Experimental hypertension induced vascular dementia: pharmacological, biochemical and behavioral recuperation by angiotensin receptor blocker and acetylcholinesterase inhibitor. Pharmacol Biochem Behav. 2012;102:101-8.
- Kurata T, Lukic V, Kozuki M, Wada D, Miyazaki K, Morimoto N, et al. Long-term effect of telmisartan on Alzheimer’s amyloid genesis in SHR-SR after tMCAO. Translat Stroke Res. 2015;6:107-15.
- Wincewicz D, Braszko JJ. Telmisartan attenuates cognitive impairment caused by chronic stress in rats. Pharmacol Rep. 2014;66:436-41.
- Wincewicz D, Braszko JJ. Angiotensin II AT1 receptor blockade by telmisartan reduces impairment of spatial maze performance induced by both acute and chronic stress. J Renin-Angiotensin-Aldosterone Sys. 2015;16:495-505.
- Tsukuda K, Mogi M, Iwanami J, Min LJ, Sakata A, Jing F, Iwai M, Horiuchi M. Cognitive deficit in amyloid-β–injected mice was improved by pretreatment with a low dose of telmisartan partly because of peroxisome proliferator-activated receptor-γ activation. Hypertension. 2009;54:782-7.
- Prusty S K, Sahu P K, Subudhi B. Angiotensin mediated oxidative stress and neuroprotective potential of antioxidants and AT1 receptor blockers. Mini Reviews in Medicinal Chemistry. 2017;17(6):518-28.
- Mishra SK, Rout K, Prusty SK, Sahu PK. Shodhana decreases nootropic activity of Semecarpus anacardium. Asian J Pharm Clin Res. 2016;2:294-7.
- Prusty SK, Pati AK, Subudhi BB, Sahu PK. Chronic forced swimming induced stress alters behavioural, histological and anti-oxidant status. Ind Drug. 2017;54:6.
- Das MK, Tiwari P, Prusty SK, Sahu PK. Neuroprotective potential of metformin against forced swimming induced neurodegeneration Wistar albino rats. Asian J Biol Sci. 2018;11:89-97.
- Salissou MT, Mahaman YA, Zhu F, Huang F, Wang Y, Xu Z, Ke D, Wang Q, Liu R, Wang JZ, Zhang B. Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats. Aging. 2018;10:3229.
- Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012;148:1204-22.
- Llansola M, Miñana MD, Montoliu C, Saez R, Corbalán R, Manzo L, Felipo V. Prenatal exposure to aluminum reduces expression of neuronal nitric oxide synthase and of soluble guanylate cyclase and impairs glutamatergic neurotransmission in rat cerebellum. J Neurochem. 1999;73:712-8.
- Savaskan E. The role of the brain renin-angiotensin system in neurodegenerative disorders. Curr Alzheimer Res. 2005;2:29-35.
- Kerr DS, Bevilaqua LR, Bonini JS, Rossato JI, Köhler CA, Medina JH, Izquierdo I, Cammarota M. Angiotensin II blocks memory consolidation through an AT2 receptor-dependent mechanism. Psychopharmacology. 2005;179:529-35.
- Indumathy S, Kavimani S, Raman KV. Role of angiotensin antagonists in memory enhancement. Int J Pharm Bio Sci. 2010;1:1-4.
- Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ. 2010;340.
- Jung KH, Chu K, Lee ST, Kim SJ, Song EC, Kim EH, et al. Blockade of AT1 receptor reduces apoptosis, inflammation, and oxidative stress in normotensive rats with intracerebral hemorrhage. J Pharmacol Exp Ther. 2007;322:1051-8.
- Khalifa M, Safar MM, Abdelsalam RM, Zaki HF. Telmisartan protects against aluminum-induced Alzheimer-like pathological changes in rats. Neurotox Res. 2020;37:275-85.
- Sodhi RK, Singh N, Jaggi AS. Neuroprotective mechanisms of peroxisome proliferator-activated receptor agonists in Alzheimer’s disease. Naunyn-Schmiedeberg's Arch Pharmacol. 2011;384:115-24.
- Glatz T, Stöck I, Nguyen-Ngoc M, Gohlke P, Herdegen T, Culman J, Zhao Y. Peroxisome-proliferator-activated receptors γ and peroxisome-proliferator-activated receptors β/δ and the regulation of interleukin 1 receptor antagonist expression by pioglitazone in ischaemic brain. J Hypert. 2010;28:1488-97.
- Yamada K, Uchida S, Takahashi S, Takayama M, Nagata Y, Suzuki N, Shirakura S, Kanda T. Effect of a centrally active angiotensin-converting enzyme inhibitor, perindopril, on cognitive performance in a mouse model of Alzheimer's disease. Brain Res. 2010;1352:176-86.
- Alzahrani YM, Sattar MA, Kamel FO, Ramadan WS, Alzahrani YA. Possible combined effect of perindopril and Azilsartan in an experimental model of dementia in rats. Saudi Pharm J. 2020;28:574-81.
- Gao Q, Ou Z, Jiang T, Tian YY, Zhou JS, Wu L, Shi JQ, Zhang YD. Azilsartan ameliorates apoptosis of dopaminergic neurons and rescues characteristic parkinsonian behaviors in a rat model of Parkinson’s disease. Oncotarget. 2017;8:24099.
- Singh NA, Bhardwaj V, Ravi C, Ramesh N, Mandal AK, Khan ZA. EGCG nanoparticles attenuate aluminum chloride induced neurobehavioral deficits, beta amyloid and tau pathology in a rat model of Alzheimer’s disease. Front Aging Neurosci. 2018:244.