Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver

This study examined in vivo effects of 2,2’,4,4’,5-pentabromodiphenyl ether (BDE-99) on the liver of Wistar Albino rats (250-300 gr) in doses of 0.05 mg/kg and 0.1 mg/kg for ten days by gavage. Our objective was to investigate the effects of BDE-99 on the apoptotic process in the liver. Previous stu...

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Main Authors: Elvan Bakar, Deniz Yüksel Yence, Ayşegül Çerkezkayabekir
Format: Article
Language:English
Published: Trakya University 2025-04-01
Series:Trakya University Journal of Natural Sciences
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Online Access:https://dergipark.org.tr/en/download/article-file/3435717
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author Elvan Bakar
Deniz Yüksel Yence
Ayşegül Çerkezkayabekir
author_facet Elvan Bakar
Deniz Yüksel Yence
Ayşegül Çerkezkayabekir
author_sort Elvan Bakar
collection DOAJ
description This study examined in vivo effects of 2,2’,4,4’,5-pentabromodiphenyl ether (BDE-99) on the liver of Wistar Albino rats (250-300 gr) in doses of 0.05 mg/kg and 0.1 mg/kg for ten days by gavage. Our objective was to investigate the effects of BDE-99 on the apoptotic process in the liver. Previous studies have shown that BDE-99 causes accumulation and oxidative damage in various tissues, especially the liver. Although the primary mechanism of BDE-99 toxicity is known to involve oxidative stress, limited information is available on its specific impact on apoptosis. Therefore, immunoreactivity of Proliferating Cell Nuclear Antigen (PCNA), Vimentin and Topoisomeraz2A (TOP2A) and Topoisomeraz2B (TOP2B) and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) were determined in the liver. Superoxide dismutase (SOD), Glutathione peroxidase (GPX) and Catalase (CAT) activities were measured in the liver. qRT-PCR analyses for the p53, Bax, Bcl-2, PCNA and Vimentin genes were carried out from paraffin-embedded liver tissues. Cell membrane damage, hypertrophy, endothelial injury, mononuclear cell infiltration in the liver were determined by Hematoxylin & Eosin. Immunoreactivity of TUNEL, Vimentin, TOP2A and TOP2B increased in both doses, but immunoreactivity of PCNA significantly increased only 0.1 mg/kg BDE-99 dose (p < 0.05). SOD and GPX activities increased but CAT activity decreased significantly (p < 0.05) in the liver. Bax, Bcl-2, PCNA, Vimentin gene expressions increased in a dose-dependent manner and p53 expression increased only in 0.1 mg/kg BDE-99. In conclusion, our results point out BDE-99 inducing apoptosis of the intrinsic mitochondrial pathway in rat liver and indicate that exposure to BDE-99 is possible to be a potential risk factor for liver diseases.
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issn 2528-9691
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publishDate 2025-04-01
publisher Trakya University
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series Trakya University Journal of Natural Sciences
spelling doaj-art-6aa1d3909f824348889db41cdf9d35102025-08-20T03:53:23ZengTrakya UniversityTrakya University Journal of Natural Sciences2528-96912025-04-01261293710.23902/trkjnat.136684269Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liverElvan Bakar0https://orcid.org/0000-0001-5703-3469Deniz Yüksel Yence1https://orcid.org/0000-0001-8696-9725Ayşegül Çerkezkayabekir2https://orcid.org/0000-0001-5537-1042TRAKYA ÜNİVERSİTESİTRAKYA ÜNİVERSİTESİTRAKYA ÜNİVERSİTESİThis study examined in vivo effects of 2,2’,4,4’,5-pentabromodiphenyl ether (BDE-99) on the liver of Wistar Albino rats (250-300 gr) in doses of 0.05 mg/kg and 0.1 mg/kg for ten days by gavage. Our objective was to investigate the effects of BDE-99 on the apoptotic process in the liver. Previous studies have shown that BDE-99 causes accumulation and oxidative damage in various tissues, especially the liver. Although the primary mechanism of BDE-99 toxicity is known to involve oxidative stress, limited information is available on its specific impact on apoptosis. Therefore, immunoreactivity of Proliferating Cell Nuclear Antigen (PCNA), Vimentin and Topoisomeraz2A (TOP2A) and Topoisomeraz2B (TOP2B) and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) were determined in the liver. Superoxide dismutase (SOD), Glutathione peroxidase (GPX) and Catalase (CAT) activities were measured in the liver. qRT-PCR analyses for the p53, Bax, Bcl-2, PCNA and Vimentin genes were carried out from paraffin-embedded liver tissues. Cell membrane damage, hypertrophy, endothelial injury, mononuclear cell infiltration in the liver were determined by Hematoxylin & Eosin. Immunoreactivity of TUNEL, Vimentin, TOP2A and TOP2B increased in both doses, but immunoreactivity of PCNA significantly increased only 0.1 mg/kg BDE-99 dose (p < 0.05). SOD and GPX activities increased but CAT activity decreased significantly (p < 0.05) in the liver. Bax, Bcl-2, PCNA, Vimentin gene expressions increased in a dose-dependent manner and p53 expression increased only in 0.1 mg/kg BDE-99. In conclusion, our results point out BDE-99 inducing apoptosis of the intrinsic mitochondrial pathway in rat liver and indicate that exposure to BDE-99 is possible to be a potential risk factor for liver diseases.https://dergipark.org.tr/en/download/article-file/3435717bde99apoptosistunelimmunohistochemistryantioxidant enzymesqrt-pcr
spellingShingle Elvan Bakar
Deniz Yüksel Yence
Ayşegül Çerkezkayabekir
Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
Trakya University Journal of Natural Sciences
bde99
apoptosis
tunel
immunohistochemistry
antioxidant enzymes
qrt-pcr
title Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
title_full Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
title_fullStr Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
title_full_unstemmed Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
title_short Brominated flame retardant BDE-99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
title_sort brominated flame retardant bde 99 promotes apoptosis by intrinsic mitochondrial pathway in rat liver
topic bde99
apoptosis
tunel
immunohistochemistry
antioxidant enzymes
qrt-pcr
url https://dergipark.org.tr/en/download/article-file/3435717
work_keys_str_mv AT elvanbakar brominatedflameretardantbde99promotesapoptosisbyintrinsicmitochondrialpathwayinratliver
AT denizyukselyence brominatedflameretardantbde99promotesapoptosisbyintrinsicmitochondrialpathwayinratliver
AT aysegulcerkezkayabekir brominatedflameretardantbde99promotesapoptosisbyintrinsicmitochondrialpathwayinratliver