Eicosapentaenoic acid ablates valproate-induced liver oxidative stress and cellular derangement without altering its clearance rate: Dynamic synergy and therapeutic utility

El‐Mowafy, Abdalla M.; Abdel-Dayem, Marwa A.; Abdel-Aziz, Azza; El-Azab, Mona F.; Said, Sameh M.

doi:10.1016/j.bbalip.2011.04.014

Cited by 24 publications

(19 citation statements)

References 35 publications

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“…EPA has been tested for the galactosamine induced liver damage in mice and results indicated that EPA was able to present hepatoprotective effects (Roy et al 2007). Also, protective effect of EPA was determined against valproate (a drug prescribed for epilepsy, bipolar affective disorder and migraine) hepatotoxicity (El-Mowafy et al 2011). In the present study, the EPA has also a pronounced effect on the relative potency of TCDD.…”

Section: Discussionmentioning

confidence: 60%

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Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes

et al. 2011

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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and ubiquitous environmental contaminant. The health impact of TCDD exposure is of great concern to the general public. Recent reports have implied that eicosapentaenoic acid (EPA) might be a potential chemopreventive agent and influence hepatotoxicity. The aim of the current study was to explore the effectiveness of EPA in alleviating the toxicity of TCDD on primary cultured rat hepatocytes. EPA (5, 10 and 20 lM) was added to cultures alone or simultaneously with TCDD (5 and 10 lM). Rat hepatocytes were treated with TCDD and EPA for 48 h, and then cytotoxicity was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (LMN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD but not EPA decreased cell viability. TCDD also increased TOS level and significantly decreased TAC level in rat hepatocytes in a clear dose dependent manner. On the basis of increasing doses, the dioxin caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures treated with EPA alone, TOS level did not change and the level of TAC significantly increased. The presence of EPA with TCDD minimized the toxic effects of the dioxin on primary hepatocytes cultures. Noteworthy, EPA has a protective effect against TCDD-mediated DNA damages.

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Section: Discussionmentioning

confidence: 60%

“…EPA exhibited significant neuroprotective potential in neurological injuries (Dyall and Michael-Titus 2008). This fatty acid can act as hepatoprotective agent (Roy et al 2007;El-Mowafy et al 2011). In the last years, there has been a renewed interest in the biological activities of EPA.…”

Section: Introductionmentioning

confidence: 99%

Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes

et al. 2011

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“…Valproic acid also has anti-inflammatory effects (16). On the other hand, in some cases, VPA augments inflammatory responses; patients receiving VPA may well develop hemorrhagic pancreatitis, bone marrow suppression, and hepatotoxicity (17,18). Gingival overgrowth and progression of gingival inflammation are sometimes observed in patients who are taking VPA chronically (19).…”

Section: Introductionmentioning

confidence: 98%

Valproic Acid Increases Susceptibility to Endotoxin Shock Through Enhanced Release of High-Mobility Group Box 1

Sugiura¹,

Ishihara

Komatsu³

et al. 2011

Shock

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High-mobility group box 1 (HMGB1) is a nuclear factor and a secreted protein. During inflammation, HMGB1 is secreted into the extracellular space where it can interact with the receptor for advanced glycation end products and trigger proinflammatory signals. Extracellular HMGB1 plays a critical role in several inflammatory diseases such as sepsis and rheumatoid arthritis. Valproic acid (VPA) is one of the most frequently prescribed antiepileptic drugs. The present study was undertaken to investigate the effect of VPA on secretion of HMGB1 in systemic inflammatory responses induced by lipopolysaccharide. Pretreatment with VPA increased the susceptibility of mice to lipopolysaccharide in endotoxemia. Valproic acid induced HMGB1 release and nuclear factor κB activation in RAW-blue cells. Valproic acid promoted the phosphorylation of ERK1/2 but not that of p38 or JNK. The MEK1/2 inhibitor PD98059 also suppressed HMGB1 release and activation of nuclear factor κB induced by VPA. Valproic acid induced expression of γ-aminobutyric acid receptors in macrophages, and picrotoxin, a γ-aminobutyric acid A receptor antagonist, inhibited the VPA-activated phosphorylation of ERK and VPA-induced HMGB1 release. These results suggest that VPA may exacerbate innate immune responses to endotoxin through enhanced release of HMGB1.

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“…Lee et al (2008) determined that Omega-3 fatty acid can repair hepatocellular damage caused by obstruction of the bile ducts 36 ; it was also shown that fish oil along with allopurinol And verapamil improve hepatic injuries resulting from ischemia by a significant reduction in oxidative stress and hepatic enzymes 37 .In a study by Mardones et al (2012), it was demonstrated that combination of thyroid hormone and fish oil protocol prevents liver damage resulted from tissue injury and ischemia 38 .Furthermore, Omega-3 fatty acid prevents acute liver defects and stimulates liver regeneration following 90% hepatectomy in rats 39 . Chiang et al (2009) showed that fish oil can stimulate anti cell proliferation effect of 1-alpha 25-dihydroxy vitamin D3 on hepatic cancer cells 40 ; EPA can also improve hepatic toxicity, oxidative stress and inflammation induced by valproate 41 .…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Fish Oil Omega-3 Supplement on Liver-related Biochemical Factors Changes Induced by Thioacetamide in Male Rats

Moghadamnia¹,

Mokhtari²,

Khatamsaz³

2016

Biosci., Biotech. Res. Asia

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Exposure to thioacetamide causes hepatotoxicity and hepatocellular carcinoma in human, while fish oil Omega-3 supplement has anti-inflammatory effects. In this study, the protective effect of Fish oil Omega-3 supplement against liver-related biochemical factors changes induced by thioacetamide in rat is investigated.42 male rats were divided into 6 groups of seven. The control group, The sham 1 group receiving 0.4ml/kg olive oil as the solvent of Fish oil Omega-3 supplement, the sham2 group inter peritonealy receiving a dose of 150 mg/kg thioacetamide at the end of the experiment, the experimental groups 1, 2 and 3 orally receiving a daily dose of 100, 200 and 300 mg/kg Fish oil Omega-3 supplements respectively for 3 month followed by an inter peritoneal dose of 150 mg/kg thioacetamide at the end of the experiment. The serum levels of GGT, LDH, albumin and total protein were measured. Following hematoxylin-eosin staining, liver tissue samples were pathologically studied.The mean level of Albumin showed a significant reduction in experimental groups 1, 2 and 3 receiving thioacetamide. Also, the mean concentration of GGT In the experimental groups 1 and 2 compared to the group receiving thioacetamide decreased significantly; whereas, the mean levels of LDH and total protein showed no significant changes in the experimental groups 1, 2, and 3 (pd"0.05). The results of this study indicate that Fish oil Omega-3 supplement has a protective effect on liver-related biochemical factors changes induced by thioacetamide in rat.

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Eicosapentaenoic acid ablates valproate-induced liver oxidative stress and cellular derangement without altering its clearance rate: Dynamic synergy and therapeutic utility

Cited by 24 publications

References 35 publications

Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes

Eicosapentaenoic acid protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced hepatic toxicity in cultured rat hepatocytes

Valproic Acid Increases Susceptibility to Endotoxin Shock Through Enhanced Release of High-Mobility Group Box 1

Protective Effects of Fish Oil Omega-3 Supplement on Liver-related Biochemical Factors Changes Induced by Thioacetamide in Male Rats

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