In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat

Usuki, Fusako; Yasutake, Akira; Umehara, Fujio; Tokunaga, Hidehiro; Matsumoto, Mutsuo; Eto, Komyo; Ishiura, Shoichi; Higuchi, Itsuro

doi:10.1016/s0304-3940(01)01764-5

Cited by 83 publications

(61 citation statements)

References 16 publications

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“…However, the inhibitory effect of mercury on antioxidative system is described more frequently [4,24]. This effect has been usually mediated by mercury-induced inhibition of antioxidant enzymes and decrease of glutahione [6,9,25,26] or vitamins such as tocopherol [27] and ascorbic acid [28]. In this study, anti-atherosclerotic mechanisms coupled with HDL (indicated by negative linear correlation between HDL-C and IMT) appeared only in non-smokers exposed to mercury vapour.…”

Section: Hg-u Concentration and Carotid Arterial Imt O R I G I N A L mentioning

confidence: 64%

The dependence between urinary mercury concentration and carotid arterial intima-media thickness in workers occupationally exposed to mercury vapour

Skoczyńska¹,

Poręba²,

Steinmentz-Beck³

et al. 2009

International Journal of Occupational Medicine and Environmental Health

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Objectives: Mechanisms of the mercury effect on arterial vessel walls include increased free radicals generation, decreased nitric oxide synthesis and increased reactivity to vasoconstrictors, leading to accelerated development of atherosclerosis and arterial hypertension. The aim of this study was to evaluate the correlation between urinary mercury (Hg-U) concentration and carotid intima-media thickness (IMT) or intraventricular septum diastolic diameter (IVSDD) to find the best markers of mercury cardiovascular toxicity. Materials and Methods: The study included 154 workers of a chemical factory using mercury in chlorine production. Urinary mercury concentration was determined by atomic absorption spectrophotometry. Serum lipids were assessed by routine methods using enzymatic assay. Serum total antioxidant status (TAS) was determined by colorimetry. Measurements of IMT and IVSDD were made by ultrasound imaging using MEDISON SA 9900 PRIME system. Results: The mean Hg-U concentration was 1.9±2.7 μg/g creatinine in women (n = 29) and 5.6±12.2 μg/g creatinine in men (n = 125). In the group of non-smokers (n = 102) there was a positive linear correlation between Hg-U concentration and IMT (r = 0.1728; p < 0.05) and a negative dependence between high density cholesterol (HDL-C) and IMT (r = -0.2109; p < 0.01). The negative linear correlation between serum total antioxidant status (TAS) and carotid IMT (r = -0.2142; p < 0.05), and the positive correlation between HDL-C and TAS (r = 0.1953; p < 0.05) were shown to be valid for the total studied group. Serum lipids in women were normal, but in men the mean triglyceride level was higher than normal. Conclusions: The occupational exposure to mercury vapour remains in a relationship with early, asymptomatic carotid atherosclerosis. The dependence between urinary mercury elimination and carotid intima-media thickness is evidenced in non-smoking workers. Defensive anti-atherosclerotic mechanisms in these workers are strongly related with HDL. In smokers, these protective mechanisms are disturbed.

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Section: Hg-u Concentration and Carotid Arterial Imt O R I G I N A L mentioning

confidence: 64%

The dependence between urinary mercury concentration and carotid arterial intima-media thickness in workers occupationally exposed to mercury vapour

Skoczyńska¹,

Poręba²,

Steinmentz-Beck³

et al. 2009

International Journal of Occupational Medicine and Environmental Health

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“…Lower doses of trolox than used in the present study clearly reduced methylmercury-induced toxicity in rats. 39 These studies suggest that trolox may decrease toxicity associated with a broad spectrum of compounds.…”

Section: Discussionmentioning

confidence: 99%

Trolox enhances the anti-lymphoma effects of arsenic trioxide, while protecting against liver toxicity

et al. 2007

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Arsenic trioxide (As 2 O 3 ) is an effective therapy in acute promyelocytic leukemia (APL), but its use in other malignancies is limited by the higher concentrations required to induce apoptosis. We have reported that trolox, an analogue of a-tocopherol, increases As 2 O 3 -mediated apoptosis in a variety of APL, myeloma and breast cancer cell lines, while nonmalignant cells may be protected. In the present study, we extended previous results to show that trolox increases As 2 O 3 -mediated apoptosis in the P388 lymphoma cell line in vitro, as evidenced by decrease of mitochondrial membrane potential and release of cytochrome c. We then sought to determine whether this combination can enhance antitumor effects while protecting normal cells in vivo. In BDF 1 mice, trolox treatment decreased As 2 O 3 -induced hepatomegaly, markers of oxidative stress and hepatocellular damage. In P388 tumor-bearing mice, As 2 O 3 treatment prolonged survival, and the addition of trolox provided a further significant increase in lifespan. In addition, the combination of As 2 O 3 and trolox inhibited metastatic spread, and protected the tumor-bearing mice from As 2 O 3 liver toxicity. Our results suggest, for the first time, that trolox might prevent some of the clinical manifestations of As 2 O 3 -related toxicity while increasing its pro-apoptotic capacity and clinical efficacy in hematological malignancies.

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“…Antioxidative enzymes and antioxidants, for example, reduce the toxicity of methylmercury (Naganuma et al, 1998;Usuki et al, 2001;Watanabe et al, 2009). According to several reports, the ubiquitin proteasome system, a selective proteolysis pathway, plays an important role in reducing the toxicity of methylmercury Hwang et al, , 2005Hwang et al, , 2007Hwang et al, and 2009.…”

Section: Introductionmentioning

confidence: 99%

siRNA-mediated AMPK.ALPHA.1 subunit gene PRKAA1 silencing enhances methylmercury toxicity in HEK293 cells

et al. 2010

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-The environmental pollutant methylmercury is a potent neurotoxin. The mechanisms of toxicity and biological defense remain largely unknown. We found that inhibiting the expression of PRKAA1 (AMPKα1), an activated subunit of AMP-activated protein kinase (AMPK), increased susceptibility of HEK293 cells to methylmercury toxicity. Treatment of the cells with AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside), an AMPK activator, reduced the methylmercury toxicity. Here, we suggest for the first time that the activation (phosphorylation) of AMPK may play an important role in reducing the toxicity of methylmercury.

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In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat

Cited by 83 publications

References 16 publications

The dependence between urinary mercury concentration and carotid arterial intima-media thickness in workers occupationally exposed to mercury vapour

The dependence between urinary mercury concentration and carotid arterial intima-media thickness in workers occupationally exposed to mercury vapour

Trolox enhances the anti-lymphoma effects of arsenic trioxide, while protecting against liver toxicity

siRNA-mediated AMPK.ALPHA.1 subunit gene PRKAA1 silencing enhances methylmercury toxicity in HEK293 cells

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