Ellagic acid attenuates liver toxicity induced by valproic acid in rats

Abdelkader, Noha F.; El-Yamany, Mohammed F.; Gad, Amany M.; Assaf, Naglaa; Fawzy, Hala M.; Elesawy, Wesam H.

doi:10.1016/j.jphs.2020.01.007

Cited by 62 publications

(32 citation statements)

References 52 publications

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“…[31] VPA toxicity to liver and kidney in the experimental and clinical studies is well-documented, while VPAinduced lung injury was reported in only a few case reports. [9,32,33] Abdelkader et al [8] detected that VPA administration resulted in a marked elevation in hydroxyproline and led to liver fibrosis. On the contrary, the therapeutic potential of VPA was experimentally shown on pulmonary hypertension, lipopolysaccharide-induced acute lung injury, and lung cancer.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of vitamin U on valproic acid‐induced lung toxicity in rats via amelioration of oxidative stress

Öztay

Tunalı

Kayalar

et al. 2020

J Biochem & Molecular Tox

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Vitamin U (Vit U) is a novel free-radical scavenger. The protective effect of Vit U on valproic acid (VPA)-induced lung damage was examined. Rats were divided into four groups: control rats; rats given Vit U (50 mg/kg/d, by gavage) for 15 days; rats treated with VPA (500 mg/kg/d, intraperitoneally) for 15 days; and rats were given VPA + Vit U (in same dose and time). On the 16th day of the experiment, the lungs were collected from rats. Lung structure, pulmonary oxidant/antioxidant parameters and Nrf2, α-SMA, and collagen-1 were evaluated by microscopic and biochemical analysis. Additionally, it was determined the interactions of Vit U with Nrf2 and Keap1 by in silico analysis. VPA administration increased lipid peroxidation and the activity of lactate dehydrogenase and myeloperoxidase. However, it decreased the glutathione level, and the activities of glutathione peroxidase, glutathione-Stransferase, catalase, and superoxide dismutase. VPA-mediated oxidative stress prompted structural distortion and fibrotic alterations in the lung. Vit U supplementation reversed structural and biochemical alterations, induced antioxidant system through Nrf2 activation, and attenuated fibrosis by reducing collagen expression in VPA-administered rats. However, Vit U pretreatment was unable to reduce α-SMA levels in the lung of VPA-treated rats. Molecular docking analysis showed the binding of Vit U to ETGE motif leads to dissociation of Nrf2 from the Nrf2/Keap1 complex and its transfer to nuclei. In conclusion, Vit U attenuated VPA-induced tissue damage by restoring antioxidative systems through amelioration of Nrf2 activity in the lung under oxidative stress.

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Section: Discussionmentioning

confidence: 99%

The protective effect of vitamin U on valproic acid‐induced lung toxicity in rats via amelioration of oxidative stress

Öztay

Tunalı

Kayalar

et al. 2020

J Biochem & Molecular Tox

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“…sedation, anxiety, and depression (Auditeau et al, 2019;Elyamany et al, 2020;Thomas, Priano, & Smith, 2020). Antiepileptic drugs are found to cause oxidative damage by increasing free radical production (Obay, Taşdemir, Tümer, Bilgin, & Atmaca, 2008).…”

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confidence: 99%

The effects of chard on brain damage in valproic acid‐induced toxicity

2020

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Valproic acid or valproate (VPA; 2-propyl valeric acid)-a branched chain carboxylic acid-is the most commonly used as anticonvulsant medication due to its broad effect on several categories of seizure (Duncan, Sander, Sisodiya, & Walker, 2006). Also, it acts as mood stabilizer, therefore, recommended for borderline personality disorder, schizoaffective disorders, social phobias, bipolar disorders, schizophrenia, and impulse disorders (Haddad, Das, Ashfaq, & Wieck, 2009). Besides the positive effects, there was reported that it has antagonistic effects on the function and development of brain. More so, some of these agents are accompanied liver toxicity,

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“…Nevertheless, no substantial alterations were detected in these three parameters ( Figure 7 c–e). Interestingly, E has elicited a hepatoprotective effect against valproic acid-provoked hepatic injury in rats [ 41 ]. Our formulations did not cause serious organ toxicities and thus did not have obvious effects to alleviate the heart-, liver-, and kidney-related toxicities.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrion-Directed Nanoparticles Loaded with a Natural Compound and a microRNA for Promoting Cancer Cell Death via the Modulation of Tumor Metabolism and Mitochondrial Dynamics

Lo¹,

Wang²,

Chen³

et al. 2020

Pharmaceutics

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Mitochondrial dysfunction may cause cancer and metabolic syndrome. Ellagic acid (abbreviated as E), a phytochemical, possesses anticancer activity. MicroRNA 125 (miR-125) may regulate metabolism. However, E has low aqueous solubility, and miR-125 is unstable in a biological fluid. Hence, this study aimed to develop nanoparticle formulations for the co-treatment of miR-125 and E. These nanoparticles were modified with one mitochondrion-directed peptide and a tumor-targeted ligand, and their modulating effects on mitochondrial dysfunction, antitumor efficacy, and safety in head and neck cancer (HNC) were evaluated. Results revealed that miR-125- and E-loaded nanoparticles effectively targeted cancer cells and intracellular mitochondria. The co-treatment significantly altered cellular bioenergetics, lipid, and glucose metabolism in human tongue squamous carcinoma SAS cells. This combination therapy also regulated protein expression associated with bioenergenesis and mitochondrial dynamics. These formulations also modulated multiple pathways of tumor metabolism, apoptosis, resistance, and metastasis in SAS cells. In vivo mouse experiments showed that the combined treatment of miR-125 and E nanoparticles exhibited significant hypoglycemic and hypolipidemic effects. The combinatorial therapy of E and miR-125 nanoparticles effectively reduced SAS tumor growth. To our best knowledge, this prospective study provided a basis for combining miRNA with a natural compound in nanoformulations to regulate mitochondrial dysfunction and energy metabolism associated with cancer.

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Ellagic acid attenuates liver toxicity induced by valproic acid in rats

Cited by 62 publications

References 52 publications

The protective effect of vitamin U on valproic acid‐induced lung toxicity in rats via amelioration of oxidative stress

The protective effect of vitamin U on valproic acid‐induced lung toxicity in rats via amelioration of oxidative stress

The effects of chard on brain damage in valproic acid‐induced toxicity

Mitochondrion-Directed Nanoparticles Loaded with a Natural Compound and a microRNA for Promoting Cancer Cell Death via the Modulation of Tumor Metabolism and Mitochondrial Dynamics

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