Investigation of the Effects of Edaravone on Valproic Acid Induced Tissue Damage in Pancreas

Oktay, Şule; Alev-Tüzüner, Burçin; Tunalı, Sevim; Ak, Esin; Emekli-Alturfan, Ebru; Tunalı-Akbay, Tuğba; Koç-Öztürk, Leyla; Çetınel, Şule; Yanardağ, Refiye; Yarat, Ayşen

doi:10.12991/marupj.319312

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Examination of the pancreas by light microscope in our study revealed that VPA treatment led to vacuolated and eosinophilic fibrillar cytoplasm in some acinar cells. These findings coincide with that reported by [ 53 ]. They stated that vacuolization and eosinophilic fibrillar patterns in the acinar cell cytoplasm might be potential factors for cellular digestion.…”

Section: Discussionsupporting

confidence: 93%

The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study

Ghoneim

Alrefai

Elsamanoudy

et al. 2020

Biology

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Background: Sodium valproate (VPA) is an antiepileptic drug (AED) licensed for epilepsy and used during pregnancy in various indications. Alpha-lipoic acid (ALA) is a natural compound inducing endogenous antioxidant production. Our study aimed to investigate the effect of prenatal administration of VPA on the pancreas of rat offspring and assess the potential protective role of ALA co-administration during pregnancy. Methods: Twenty-eight pregnant female albino rats were divided into four groups: group I (negative control), group II (positive control, ALA treated), group III (VPA-treated), and group IV (VPA-ALA-treated). The pancreases of the rat offspring were removed at the fourth week postpartum and prepared for histological, immune-histochemical, morphometric, molecular, and oxidative stress marker studies. Results: In group III, there were pyknotic nuclei, vacuolated cytoplasm with ballooning of acinar, α, and β cells of the pancreas. Ultrastructural degeneration of cytoplasmic organelles was detected. Additionally, there was a significant increase in oxidative stress, a decrease in insulin-positive cell percentage, and an increase in glucagon positive cells in comparison to control groups. Moreover, VPA increased the gene expression of an apoptotic marker, caspase-3, with a decrease in anti-apoptotic Bcl2 and nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional factor. Conversely, ALA improved oxidative stress and apoptosis in group VI, and a consequent improvement of the histological and ultrastructure picture was detected. Conclusion: ALA co-administration with VPA significantly improved the oxidative stress condition, histological and morphometric picture of the pancreas, and restored normal expression of related genes, including Nrf2, caspase-3, and Bcl-2. Administration of α-lipoic acid has a protective effect against VPA-induced pancreatic oxidative damage via its cytoprotective antioxidant effect.

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Section: Discussionsupporting

confidence: 93%

The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study

Ghoneim

Alrefai

Elsamanoudy

et al. 2020

Biology

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“…Decreased activities of CAT, SOD, and GPx enzymes were reported by Vidya and Subramanian [ 66 ] who conducted research on the effects of valproate‐sodium salt (SVP) on the liver and kidney. In another study, Oktay et al [ 67 ] revealed that VPA‐induced pancreatic damage causes a decline in the activities of the same enzymes mentioned above. El‐Shenawy and Hamza [ 68 ] reported that activities of CAT, SOD, glutathione‐related enzymes declined when rats were treated with different doses of SVP.…”

Section: Discussionmentioning

confidence: 96%

The effects of edaravone, a free‐radical scavenger in lung injury induced by valproic acid demonstrated via different biochemical parameters

Bayrak

Yılmaz

Cakmak

et al. 2021

J Biochem & Molecular Tox

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In this study, we aimed to evaluate whether edaravone (EDA) has a protective role against valproic acid (VPA)-induced lung damage via its antioxidative activity. Male Sprague-Dawley rats were split into four groups. Control (n = 8) rats; rats given EDA (30 mg kg −1 day −1 ; n = 10); rats given only (VPA, 500 mg kg −1 day −1 ; n = 10); rats given VPA + EDA (in the same dose and time) for 7 days. EDA and VPA were applied intraperitoneally. After 8 days, lung tissues were immediately taken from the rats. In lung homogenates, reduced glutathione, total antioxidant status levels, and superoxide dismutase, glutathione peroxidase, sodium/potassium ATPase, paraoxonase1, and carbonic anhydrase activities significantly abated, whereas catalase, glutathione reductase, glutathione-S-transferase activities insignificantly decreased in the VPA-treated group. In contrast, lipid peroxidation, reactive oxygen species, and total oxidant status levels, glycoprotein and protein carbonyl contents, nitric oxide, hydroxyproline levels, and xanthine oxidase, lactate dehydrogenase, arginase, and prolidase activities significantly increased in the VPA-given group. Administration of EDA caused the reverse effects. As a consequence, EDA prevented oxidative stress-mediated lung injury via its robust antioxidant effects.

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“…Ultrastructurally, there were shrunken heterochromatic nuclei with irregularity, dilated rough endoplasmic reticulum and perinuclear space and swollen disrupted mitochondria in the acinar cells and beta cells. These adverse findings of valproic acid administration were supported by some researchers who reported that valproic acid caused disturbance of the normal structure of the pancreas causing acute pancreatitis [1,34] . Moreover, no significant ultrastructural changes were observed in alpha cells of VA-treated rats.…”

Section: Discussionmentioning

confidence: 67%

“…Valproic acid (VA) and its salts, mainly sodium valproate, are effective antiepileptic and anticonvulsant drugs [1] . It was approved by Food and Drug Administration since 1978 [2] .…”

Section: Introductionmentioning

confidence: 99%

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Marjoram Oil Attenuates Valproic Acid-Induced Pancreatic Damage in Adult Male Albino Rats: A Histological and Immunohistochemical Study

Kassab

Eldin

Abd-El-Hafez

2022

Egyptian Journal of Histology

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Introduction:Valproic acid [VA] is an antiepileptic drug that is extensively prescribed for many neurological disorders. Its use is associated with serious pancreatic complications. Marjoram oil [MO] is a health protective agent with proved anti-oxidant activity. Aim: Study of the effect of valproic acid on pancreas of adult male albino rats exploring novel mechanisms of VA-induced pancreatic damage and to evaluate the potential protective role of marjoram oil. Materials and Methods: Fifty adult male albino rats were used as a control group, a valproic acid group and a valproic acidmarjoram group. Both VA [200mg/kg] and MO [0.5ml/kg] were given once a day orally for eight weeks. Specimens of the pancreas were processed for light and electron microscopic studies. Immunohistochemical study was performed using anti-P53 antibodies.Results: Specimens of the valproic acid group showed an obvious distortion in the pancreatic acini as well as the islets of Langerhans. The acinar and islets cells showed cytoplasmic vacuoles and pyknotic nuclei. Large autophagic vacuoles containing an acidophilic material appeared in many cells. Dilated ducts and blood vessels were seen. There was a significant increase in the P53-immunoreaction of the acinar and islets cells and a significant decrease in the number of the zymogen granules of the acinar cells. Ultrastructurally, there were shrunken nuclei with irregularity, dilated rough endoplasmic reticulum and swollen mitochondria in the acinar cells and beta cells. In contrast, minimal changes occurred in the valproic acid-marjoram group that received MO before VA. Conclusion: Valproic acid administration to albino rats resulted in significant structural alterations in the pancreas. Marjoram oil attenuated VA effect and preserved the pancreas structure.

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Investigation of the Effects of Edaravone on Valproic Acid Induced Tissue Damage in Pancreas

Cited by 9 publications

References 24 publications

The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study

The Protective Role of Prenatal Alpha Lipoic Acid Supplementation against Pancreatic Oxidative Damage in Offspring of Valproic Acid-Treated Rats: Histological and Molecular Study

The effects of edaravone, a free‐radical scavenger in lung injury induced by valproic acid demonstrated via different biochemical parameters

Marjoram Oil Attenuates Valproic Acid-Induced Pancreatic Damage in Adult Male Albino Rats: A Histological and Immunohistochemical Study

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