Modulating effects of dietary fats on methylmercury toxicity and distribution in rats

Jin, Xiaolei; Lok, E.; Bondy, Genevieve S.; Caldwell, Douglas R.; Mueller, Robert F.; Kapal, Kamla; Armstrong, Cheryl; Taylor, Marnie; Kubow, Stan; Mehta, Rekha; Chan, Hing Man

doi:10.1016/j.tox.2006.10.023

Cited by 37 publications

(14 citation statements)

References 58 publications

(60 reference statements)

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“…Treatment of the rats with MeHg resulted in a dosedependent increase of Hg in WB and brain sections (FC, HC, and CB). This fi nding is in agreement with previous studies reported that blood levels of Hg were 12-20 fold higher than brain levels (Iverson et al, 1973;Jin et al, 2007).…”

Section: Discussionsupporting

confidence: 94%

Mercury-induced amyloid-beta (Aβ) accumulation in the brain is mediated by disruption of Aβ transport

2014

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-According to a recent study, mercury (Hg) exposure contributes to Alzheimer's disease (AD). However, the underlying mechanisms are not understood. This study investigated the effect of methylmercury (MeHg) treatment on the generation, degradation, and transport of amyloid β-protein (Aβ) in the brain. Wistar rats were administered MeHg by gavage (0, 20, 200, and 2,000 μg Hg/kg/day) for 4 weeks. The total Hg in the blood and brain regions was measured, and the levels of Aβ 42 in plasma, cerebrospinal fluid (CSF), and brain regions were estimated. The expression of amyloid precursor protein (APP), beta-site APP-cleaving enzyme 1 (BACE1), and neprilysin (NEP) in the brain regions was determined, in addition to the expression of low-density lipoprotein receptor-related protein 1 (LRP1) and the receptor for advanced glycation end products (RAGE) in the brain capillary endothelium (BCE). Finally, the amount of soluble low-density lipoprotein receptor-related protein (sLRP) in the plasma was determined. Aβ 42 levels were decreased in the CSF of the 2,000 μg Hg/kg/day group compared with controls, and Aβ 42 levels increased in the hippocampus (HC) in a dose-dependent manner. MeHg decreased LRP1 expression but increased RAGE levels in BCE. sLRP levels were decreased in the plasma of the MeHgtreated rats. They were positively correlated with CSF Aβ 42 and negatively correlated with Aβ 42 and Hg levels in HC. These results imply that MeHg reduces the transportation of Aβ, thereby resulting in the accumulation of the protein in the HC. Plasma sLRP levels may be an early biomarker of Hg-induced Aβ accumulation in the brain.

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Section: Discussionsupporting

confidence: 94%

Mercury-induced amyloid-beta (Aβ) accumulation in the brain is mediated by disruption of Aβ transport

2014

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“…The greater expression of oxidative stress in liver exposed to TCDD may be due to inactivation of the antioxidant enzymes (Jin et al 2007). Our study clearly demonstrates that a decreased ability to scavenge ROS may result from TCDD exposure, contributing to oxidative stress and thus to TCDD hepatotoxicity.…”

Section: Discussionmentioning

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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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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“…The reasons for this observation are unknown. Analysis of the lard diet indicated no detectable mercury (Jin et al, 2007).…”

Section: Mercury Content In Kidneymentioning

confidence: 97%

“…The dietary and MeHg treatment of the animals has been described in detail elsewhere (Jin et al, 2007). Briefly, male Sprague Dawley rats at weights of 217 ± 9 g and ages of 42-45 days were obtained from Charles River Canada (St Constant, Quebec, Canada).…”

Section: Animals Diets and Treatmentsmentioning

confidence: 99%

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Dietary fats altered nephrotoxicity profile of methylmercury in rats

Jin

Lok

Caldwell

et al. 2008

J of Applied Toxicology

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Weanling male Sprague-Dawley rats were administered semi-purified isocaloric diet containing soy oil (SO), seal oil (SE), docosahexaenoic acid (DHA), fish oil (FO) or lard (LA) for 28 days, and then gavaged with 0, 1 or 3 mg MeHg kg(-1) body weight per day and fed the same diet for 14 days. Serum and 24 h urine samples were collected on the day of necropsy, and analyzed for markers of kidney function and diseases. Kidney slices were analyzed for para-amino-hippurate (PAH) and tetraethylammonium (TEA) uptake, total mercury and MeHg content, and examined for pathological lesions. Total mercury and MeHg contents increased significantly and dose-dependently in all dietary groups. MeHg significantly increased relative kidney weight in all groups, serum creatinine in all except SO group, serum uric acid in the DHA and LA groups, serum Mg in all except the LA group, and urinary protein in the SO group. MeHg significantly decreased serum urea nitrogen in SE, FO and LA groups, urinary creatinine in the DHA group, PAH uptake in all except the SE group, and TEA uptake in all groups. MeHg caused nephrosis in all dietary groups. MeHg also significantly increased neutrophil counts in all except the SE group, decreased serum albumin and triglyceride in all except the DHA group, and increased serum total cholesterol in all groups, suggesting a nephrotic syndrome-like outcome. These results confirmed that kidney tubules are major targets of MeHg nephrotoxicity. Treatment with dietary fats did not prevent, but rather altered the profile of, nephrotoxicity of MeHg in rats.

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Modulating effects of dietary fats on methylmercury toxicity and distribution in rats

Cited by 37 publications

References 58 publications

Mercury-induced amyloid-beta (Aβ) accumulation in the brain is mediated by disruption of Aβ transport

Mercury-induced amyloid-beta (Aβ) accumulation in the brain is mediated by disruption of Aβ transport

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

Dietary fats altered nephrotoxicity profile of methylmercury in rats

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