Histone deacetylase 2 inhibitor valproic acid attenuates bisphenol A-induced liver pathology in male mice

Al-Griw, Mohamed A.; Alshibani, Zaynab Osama; Alghazeer, Rabia; Elhensheri, Mohamed; Tabagh, Refaat M; Eskandrani, Areej A.; Alansari, Wafa S.; Habibulla, Mahmoud M; Shamlan, Ghalia

doi:10.1038/s41598-022-12937-4

Cited by 6 publications

(6 citation statements)

References 89 publications

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“…[36] BPA also causes nephrotoxicity, hepatotoxicity, neurotoxicity, and cardiotoxicity by triggering apoptosis and ROS formation in various tissues. [20,[37][38][39] Studies are increasing day by day to reduce these negative effects of BPA. [26,40] GA has important antioxidant, anticancer, anti-inflammatory, and antiapoptotic properties.…”

Section: Discussionmentioning

confidence: 99%

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

Bayav,

Darendelioğlu,

Caglayan

2024

J Biochem & Molecular Tox

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Bisphenol A (BPA) is a synthetic environmental pollutant widely used in industry, as well as is an endocrine disrupting chemicals and has a toxic effects on heart tissue. The aim of this study is to reveal the cardioprotective effects of 18β‐glycyrretinic acid (GA) against BPA‐induced cardiotoxicity in rats. In this study, 40 male rats were used and five different groups (each group includes eight rats) were formed. The rats were applied BPA (250 mg/kg b.w.) alone or with GA (50 and 100 mg/kg b.w.) for 14 days. Rats were killed on Day 15 and heart tissues were taken for analysis. GA treatment decreased serum lactate dehydrogenase and creatine kinase MB levels, reducing BPA‐induced heart damage. GA treatment showed ameliorative effects against lipid peroxidation and oxidative stress caused by BPA by increasing the antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase, and catalase) and GSH level of the heart tissue and decreasing the MDA level. In addition, GA showed antiapoptotic effect by increasing Bcl‐2, procaspase‐3, and ‐9 protein expression levels and decreasing Bax, cytochrome c, and P53 protein levels in heart tissue. As a result, it was found that GA has cardioprotective effects on heart tissue by exhibiting antioxidant and antiapoptotic effects against heart damage caused by BPA, an environmental pollutant. Thus, it was supported that GA could be a potential cardioprotective agent.

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Section: Discussionmentioning

confidence: 99%

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

Bayav,

Darendelioğlu,

Caglayan

2024

J Biochem & Molecular Tox

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“…For liver damage test, alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) were measured using commercial kits (Biomaghreb, Tunisia) as previously described ( Al-Griw et al , 2022a ). The enzymatic-based method was used to measure the activities of the enzymes.…”

Section: Methodsmentioning

confidence: 99%

“…BPA impacts the health of humans, therefore, has gotten a lot of attention in public health. Impacts of BPA on the kidneys, lungs, heart, and liver have been demonstrated ( Tyl et al , 2008 ; Al-Griw et al , 2022a ). Recent research exhibited that BPA has detrimental effects on testicular cytoarchitecture and male reproductive performance ( Al-Griw et al , 2021a , 2022b ).…”

Section: Introductionmentioning

confidence: 99%

“…In humans and animals, the liver is a crucial organ for detoxification, and malfunction of the liver after environmental toxicant exposures is accompanied by liver pathology ( Paradies et al , 2014 ; Al-Griw et al , 2022a ). According to the vest knowledge of the authors, there are no/little studies on the role of VitD in reducing and/ or preventing liver pathology.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D ameliorates liver pathology in mice caused by exposure to endocrine disruptor bisphenol A

Griw¹,

Zaed²,

Hdud³

et al. 2023

Open Vet J

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Background: Increasing evidence suggests that bisphenol A (BPA) induces liver pathological changes. Further, an association between BPA and circulating vitamin D (VitD) levels were documented. Aim: The role of VitD in BPA-induced liver pathological changes was explored in this study. Methods: Healthy 4.5-week-old male (n=35) and female (n=35) Swiss albino mice were used in this study. The animals were randomly divided into control and treated groups. The control groups were further divided into sham (no treatment) and vehicle (corn oil), whereas the treated groups were also divided into VitD (2195U/kg), BPA (50μg/kg), and BPA+VitD (50μg/kg+2195U/kg) groups. For six weeks (twice a week), the animals were dosed intraperitoneally (IP). One week later (at 10.5-weeks-old), the animals were sacrificed for biochemical and histological analyses. Results: BPA produced a considerable rise in the body and liver weights in both genders of mice when compared to control mice. BPA also caused significant increases in the liver damage markers alanine transaminase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). It also induced liver histopathological changes, including higher apoptotic indices in both genders. On the other hand, treatment with VitD considerably reduced liver damage and slightly decreased the apoptotic index rate. The ALP, ALT, and GGT levels were also markedly reduced. VitD has been proven to have a protective effect on both genders. Conclusions: According to our findings, VitD protects mice from BPA-induced liver damage, possibly via suppressing liver damage markers.

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“…PTZ (Sigma-Aldrich, Poz- Valproic acid (VPA) is an anticonvulsant drug indicated for the treatment of epilepsy and is occasionally used in the treatment of bipolar disorder [21,22]. The mode of action of VPA remains unclear, though proposed mechanisms include modulation of GABA levels, blocking of voltage-gated sodium channels, and inhibiting histone deacetylases [23,24]. VPA is clinically available in several forms including VPA alone, sodium valproate (VPN), and VPN in combination with VPA [21].…”

Section: Animal Treatmentmentioning

confidence: 99%

Pharmacometabolic Effects of Pteryxin and Valproate on Pentylenetetrazole-Induced Seizures in Zebrafish Reveal Vagus Nerve Stimulation

Skiba

Pellegata

Morozova

et al. 2023

Cells

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Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 µM (the equivalent of 4.28 ± 0.28 µg/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 ± 0.40 µg/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1–20 µM) showed significantly higher bioavailability than VPN (0.1–5 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters.

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Histone deacetylase 2 inhibitor valproic acid attenuates bisphenol A-induced liver pathology in male mice

Cited by 6 publications

References 89 publications

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

18β‐Glycyrrhetinic acid exerts cardioprotective effects against BPA‐induced cardiotoxicity through antiapoptotic and antioxidant mechanisms

Vitamin D ameliorates liver pathology in mice caused by exposure to endocrine disruptor bisphenol A

Pharmacometabolic Effects of Pteryxin and Valproate on Pentylenetetrazole-Induced Seizures in Zebrafish Reveal Vagus Nerve Stimulation

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