Histopathologic, apoptotic and autophagic, effects of prenatal bisphenol A and/or di(2-ethylhexyl) phthalate exposure on prepubertal rat testis

Balcı, Aylin; Özkemahlı, Gizem; Erkekoğlu, Pınar; Zeybek, Naciye Dilara; Yersal, Nilgün; Koçer-Gümüşel, Belma

doi:10.1007/s11356-020-08274-6

Cited by 39 publications

(11 citation statements)

References 78 publications

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“…Because of its high quantity of polyunsaturated fatty acids (PUFAs) and a lack of antioxidant mechanisms, the hippocampus is particularly vulnerable to lipid peroxidation damage (de Freitas 2010). In response to BPA exposure, caspase-3 can play a critical role in triggering apoptosis by cleaving essential cellular proteins, resulting in morphological abnormalities and cell death (Balci et al 2020). The study noted that animals pretreated with EGCG before BPA exhibited both apoptosis and necrosis in the hippocampal neurons of the CA3 region, which can be elucidated by enhancing the activity of caspase-3 as a result of altering mitochondrial function by ROS/ RNS.…”

Section: Discussionmentioning

confidence: 93%

Does ( −)-epigallocatechin-3-gallate protect the neurotoxicity induced by bisphenol A in vivo?

Tabaa

Sokkar

Ramdan

et al. 2022

Environ Sci Pollut Res

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Bisphenol A (BPA) is one of the chemicals that is firmly accompanied by hippocampal neuronal injury. As oxidative stress appears to be a major contributor to neurotoxicity induced by BPA, antioxidants with remarkable neuroprotective effects can play a valuable protective role. Around the world, ( −)-epigallocatechin-3-gallate (EGCG) was one of the most popular antioxidants that could exert a beneficial neuroprotective role. Here, we examined the potential efficiency of EGCG against neurotoxicity induced by BPA in the hippocampal CA3 region of the rat model. This study revealed that EGCG was unable to abrogate the significant decrease in circulating adiponectin level and hippocampal superoxide dismutase activity as well as an increase in hippocampal levels of nitric oxide and malondialdehyde. Notably, EGCG failed to antagonize the oxidative inhibitory effect of BPA on hippocampal neurotransmission and its associated cognitive deficits. In addition, the histopathological examination with immunohistochemical detection of caspase-3 and NF-kB/p65 emphasized that EGCG failed to protect hippocampal CA3 neurons from apoptotic and necrotic effects induced by BPA. Our study revealed that EGCG showed no protective role against the neurotoxic effect caused by BPA, which may be attributed to its failure to counteract the BPA-induced oxidative stress in vivo. The controversial effect is probably related to EGCG’s ability to impede BPA glucuronidation and thus, its detoxification. That inference requires further additional experimental and clinical studies. Graphical abstract

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Section: Discussionmentioning

confidence: 93%

Does ( −)-epigallocatechin-3-gallate protect the neurotoxicity induced by bisphenol A in vivo?

Tabaa

Sokkar

Ramdan

et al. 2022

Environ Sci Pollut Res

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“…Cleaved caspase-3 and Bax/Bcl-2 were significantly raised, and Bcl-2 was decreased only at high doses of DEHP, but Bax was not significantly different (Zhu et al 2021 ). Balci et al found that DEHP significantly increased the apoptosis of testicular spermatogenic cells in the progeny of rats and raised the levels of caspase-8, LC3, and Beclin, while there was no difference in the levels of caspase-3 and p62 (Balci et al 2020 ). Zhao et al found that DEHP could notably increase the number of apoptotic cells, increase cleaved caspase-3 levels, and reduce the Bcl-2/Bax proportion in rat testes (Zhao et al 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…It can enter the body through the respiratory and digestive tracts and is toxic to multiple organs (Kashyap and Agarwal 2018 ; Luo et al 2018 , 2020 ). DEHP can induce autophagy and apoptosis in mouse testicular cells (Barakat et al 2017 ; Sun et al 2018 ; Wei et al 2018 ; Pan et al 2019 ; Balci et al 2020 ; Gan et al 2020 ; Zhang et al 2020 ; Zhao et al 2020 ; Zhu et al 2021 ) and damage to human sperm DNA, leading to apoptosis (Wang et al 2016a , 2016b , 2019b ). A low dose of DEHP can properly activate autophagy to protect the testis, while a high dose of DEHP can mediate apoptosis to damage the testis (Fu et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Lycium barbarum glycopeptide on renal and testicular injury induced by di(2-ethylhexyl) phthalate

Zhou

Zhang

Shi

et al. 2022

Cell Stress and Chaperones

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Di(2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant with renal and reproductive toxicity. Lycium barbarum glycopeptide (LbGp) is the main active component of Lycium barbarum, which can protect the kidney and promote reproduction. Autophagy and apoptosis are the regulatory mechanisms of cell adaptation to external stress. This study investigated whether DEHP and LbGp affect kidney and testis by regulating autophagy and apoptosis. DEHP induced apoptosis in human embryonic kidney-293 (HEK-293) cells and human kidney-2 (HK-2) cells, as well as glomerular enlargement, enhanced renal autophagy and inflammation, decreased testicular germ cells, and enhanced testicular autophagy. LbGp reduced apoptosis in HEK-293 cells and HK-2 cells, reduced glomerular enlargement and renal inflammation, enhanced renal autophagy, increased testicular germ cells, and alleviated testicular autophagy. These results suggested that DEHP induced inflammation to cause kidney injury, mildly enhanced renal autophagy, and also induced excessive autophagy, leading to testicular injury. LbGp reduced inflammation and appropriately enhanced autophagy to alleviate renal injury and also reduced excessive autophagy to alleviate testicular injury. Silent information regulator 1 (SIRT1)/forkhead box O3a (FoxO3a)-mediated autophagy and p38 mitogen-activated protein kinase (p38 MAPK)-mediated inflammation played important roles.

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“…Male rats treated per os with DEHP (50 mg/kg bw/day), DBP (50 mg/kg bw/day), BPA (25 mg/kg bw/day) and their MIX (50 mg/kg bw/day DEHP + 50 mg/kg bw/day DBP + 25 mg/kg bw/day BPA) showed more evident testicular toxicity in the MIX group (desquamated germinal epithelium cells, enlarged cells with hyperchromatic nuclei, multinucleated cells and intracytoplasmic vacuoles) in comparison with the individual chemicals, while effects on redox status were either more prominent, or present only in the MIX group, confirming that the male reproductive system might be more susceptible following exposure to chemicals in mixtures than individually [ 38 ]. Moreover, when orally administered during pregnancy and lactation, the mixture of BPA (50 mg/kg/day), DEHP (30 mg/kg/day) and their binary mixture (50 mg/kg/day BPA + 30 mg/kg/day DEHP) shows more dramatic changes in both testicular structure and cell death [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Toxicological Assessment of Oral Co-Exposure to Bisphenol A (BPA) and Bis(2-ethylhexyl) Phthalate (DEHP) in Juvenile Rats at Environmentally Relevant Dose Levels: Evaluation of the Synergic, Additive or Antagonistic Effects

Tassinari

Tait

Busani

et al. 2021

IJERPH

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Background: The general population (including children) is exposed to chemical mixtures. Plasticizers such as Bisphenol A (BPA) and Phthalates (mainly Bis(2-ethylhexyl) phthalate-DEHP) are widespread contaminants classified as endocrine disrupters which share some toxicological profiles and coexist in food and environment. Methods: To identify hazards of DEHP and BPA mixtures, the juvenile toxicity test—where rodents are in peripubertal phase of development, resembling childhood—was selected using exposure data from biomonitoring study in children. Biological activity and potential enhanced and/or reduced toxicological effects of mixtures due to common mechanisms were studied, considering endpoints of metabolic, endocrine and reproductive systems. The degree of synergy or antagonism was evaluated by synergy score calculation, using present data and results from the single compound individually administered. Results: In metabolic system, synergic interaction predominates in female and additive in male rats; in the reproductive and endocrine systems, the co-exposure of BPA and DEHP showed interactions mainly of antagonism type. Conclusions: The present approach allows to evaluate, for all the endpoints considered, the type of interaction between contaminants relevant for human health. Although the mode of action and biological activities of the mixtures are not completely addressed, it can be of paramount usefulness to support a more reliable risk assessment.

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Histopathologic, apoptotic and autophagic, effects of prenatal bisphenol A and/or di(2-ethylhexyl) phthalate exposure on prepubertal rat testis

Cited by 39 publications

References 78 publications

Does ( −)-epigallocatechin-3-gallate protect the neurotoxicity induced by bisphenol A in vivo?

Does ( −)-epigallocatechin-3-gallate protect the neurotoxicity induced by bisphenol A in vivo?

Effects of Lycium barbarum glycopeptide on renal and testicular injury induced by di(2-ethylhexyl) phthalate

Toxicological Assessment of Oral Co-Exposure to Bisphenol A (BPA) and Bis(2-ethylhexyl) Phthalate (DEHP) in Juvenile Rats at Environmentally Relevant Dose Levels: Evaluation of the Synergic, Additive or Antagonistic Effects

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