ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats

Çakır, Murat; Düzova, Halil; Tekin, Suat; Taşlıdere, Elif; Kaya, Gülşen; Çiğremiş, Yılmaz; Özgöçer, Tuba; Yoloğlu, Saim

doi:10.1016/j.lfs.2017.03.022

Cited by 21 publications

(10 citation statements)

References 43 publications

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“…In our previous study on Alzheimer's disease in rats, we found the anti-inflammatory, antiapoptotic, and antioxidant effects of ACA. 18 In our study increased TOS, OSI, and MDA levels in kidney tissue in the I/R group were reduced by ACA administration. ACA administration also increased catalase enzyme activity, which decreased in the I/R group.…”

Section: Discussionsupporting

confidence: 56%

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Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A₂ enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Çakır

Tekin

Taşlidere

et al. 2018

J of Cellular Biochemistry

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The production of reactive oxygen species and inflammatory events are the underlying mechanisms of ischemia-reperfusion injury (IRI). It was determined that transient receptor potential melastatin-2 (TRPM2) channels and phospholipase A 2 (PLA 2 ) enzymes were associated with inflammation and cell death. In this study, we investigated the effect of N-(p-amylcinnamoyl) anthranilic acid (ACA), a TRPM2 channel blocker, and PLA 2 enzyme inhibitor on renal IRI. A total of 36 male Sprague-Dawley rats were divided into four groups: control, ischemia-reperfusion (I/R), I/R + ACA 5 mg, I/R + ACA 25 mg. In I/R applied groups, the ischemia for 45 minutes and reperfusion for 24 hours were applied bilaterally to the kidneys. In the I/R group, serum levels of the blood urea nitrogen (BUN), creatinine, cystatin C (CysC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 increased. On histopathological examination of renal tissue in the I/R group, the formation of glomerular and tubular damage was seen, and it was detected that there was an increase in the levels of malondialdehyde (MDA), caspase-3, total oxidant status (TOS), and oxidative stress index (OSI); and there was a decrease in total antioxidant capacity (TAC) and catalase enzyme activity. ACA administration reduced serum levels of BUN, creatinine, CysC, KIM-1, NGAL, interleukin-18. In the renal tissue, ACA administration reduced histopathological damage, levels of caspase-3, MDA, TOS, and OSI; and it increased the level of TAC and catalase enzyme activity. It has been shown with the histological and biochemical results in this study that ACA is protective against renal IRI. K E Y W O R D S N-(p-amylcinnamoyl) anthranilic acid, phospholipase A 2 , renal ischemia-reperfusion injury, transient receptor potential melastatin-2 channels J Cell Biochem. 2019;120:3822-3832. wileyonlinelibrary.com/journal/jcb 3822 |

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Section: Discussionsupporting

confidence: 56%

“…There are no studies in the literature about the ACA effect on IRI. In our previous study on Alzheimer’s disease in rats, we found the anti‐inflammatory, antiapoptotic, and antioxidant effects of ACA . In our study increased TOS, OSI, and MDA levels in kidney tissue in the I/R group were reduced by ACA administration.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A₂ enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Çakır

Tekin

Taşlidere

et al. 2018

J of Cellular Biochemistry

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“…In vivo and in vitro, OA leads to Aβ deposition and subsequent neuronal degeneration, synaptic loss, memory impairment and tau hyperphosphorylation, all of which resemble AD pathology (25,26). OA also induces neurotoxicity of the SH-SY5Y cell line and cultured neuronal cells, resulting in the development of pathological conditions similar to AD (27).…”

Section: Discussionmentioning

confidence: 99%

Galangin decreases p‑tau, Aβ42 and β‑secretase levels, and suppresses autophagy in okadaic acid‑induced PC12 cells via an Akt/GSK3β/mTOR signaling‑dependent mechanism

Huang

Zhong

et al. 2019

Mol Med Report

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Okadaic acid (OA)-induced neurotoxicity may be considered a novel tool used to study Alzheimer's disease (AD) pathology, and may be helpful in the development of a novel therapeutic approach. It has been reported that galangin inhibits β-site amyloid precursor protein-cleaving enzyme 1 expression, which is a key enzyme for amyloid β (Aβ) generation and is a potential drug candidate for AD therapy. However, further studies are required to confirm its neuroprotective effects in other AD models. The present study aimed to explore the neuroprotective effects of galangin on OA-induced neurotoxicity in PC12 cells. The cells were divided into the following groups: Control group, model group (175 nM OA for 48 h) and galangin groups (0.25, 0.5 and 1 µg/ml). Beclin-1, phosphorylated (p)-protein kinase B (Akt), p-glycogen synthase kinase (GSK)3β and p-mechanistic target of rapamycin (mTOR) expression was also measured in the following PC12 cell groups: Control group, model group, 3-methyladenine group (5 nM), rapamycin group (100 nM) and galangin group (1 µg/ml). The levels of β-secretase, Aβ 42 and p-tau were detected by ELISA, Beclin-1 expression was examined by immunohistochemistry and the protein expression levels of p-Akt, p-mTOR p-GSK3β, and Beclin-1 were detected by western blotting. Galangin treatment enhanced cell viability in cells treated with OA, and decreased β-secretase, Aβ 42 and p-tau levels. In addition, it suppressed Beclin-1 and p-GSK3β expression, but promoted p-Akt and p-mTOR expression by regulating the Akt/GSK3β/mTOR pathway. These results indicated that galangin protected PC12 cells from OA-induced cytotoxicity and inhibited autophagy via the Akt/GSK3β/mTOR pathway, thus suggesting that it may be considered a potential therapeutic agent for AD.

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“…of AD such as tau hyperphosphorylation and Aβ formation have been reported in AD models induced by other toxic substances. Okadaic acid induced AD biomarkers through inhibition of serine/threonine phosphatase 1 (PP1) and 2A (PP2) [78]. Ibotenic acid impaired cholinergic neurons in the nucleus basalis of Meynert, a similar sign found in AD.…”

Section: Biomarkersmentioning

confidence: 75%

Toxic Substance-induced Hippocampal Neurodegeneration in Rodents as Model of Alzheimer’s Dementia

Nurmasitoh

Sari

Susilowati

2021

Open Access Maced J Med Sci

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BACKGROUND: Alzheimer’s Dementia (AD) cases are increasing with the global elderly population. To study the part of the brain affected by AD, animal models for hippocampal degeneration are still necessary to better understand AD pathogenesis and develop treatment and prevention measures. AIM: This study was a systematic review of toxic substance-induced animal models of AD using the Morris Water Maze method in determining hippocampal-related memory impairment. Our aim was reviewing the methods of AD induction using toxic substances in laboratory rodents and evaluating the report of the AD biomarkers reported in the models. METHODS: Data were obtained from articles in the PubMed database, then compiled, categorized, and analyzed. Eighty studies published in the past 5 years were included for analysis. RESULTS AND DISCUSSION: The most widely used method was intracerebroventricular injection of amyloid-β _substances. However, some less technically challenging techniques using oral or intraperitoneal administration of other toxic substances also produce successful models. Instead of hippocampal neurodegeneration, many studies detected biomarkers of the AD pathological process while some reported inflammation, oxidative stress, neurotrophic factors, and changes of cholinergic activity. Female animals were underrepresented despite a high incidence of AD in women. CONCLUSION: Toxic substances may be used to develop AD animal models characterized with appropriate AD pathological markers. Characterization of methods with the most easy-handling techniques and more studies in female animal models should be encouraged.

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ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats

Cited by 21 publications

References 43 publications

Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A₂ enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A₂ enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Galangin decreases p‑tau, Aβ42 and β‑secretase levels, and suppresses autophagy in okadaic acid‑induced PC12 cells via an Akt/GSK3β/mTOR signaling‑dependent mechanism

Toxic Substance-induced Hippocampal Neurodegeneration in Rodents as Model of Alzheimer’s Dementia

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ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats

Cited by 21 publications

References 43 publications

Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Galangin decreases p‑tau, Aβ42 and β‑secretase levels, and suppresses autophagy in okadaic acid‑induced PC12 cells via an Akt/GSK3β/mTOR signaling‑dependent mechanism

Toxic Substance-induced Hippocampal Neurodegeneration in Rodents as Model of Alzheimer’s Dementia

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Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A₂ enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

Protective effect of N‐(p‐amylcinnamoyl) anthranilic acid, phospholipase A₂ enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury