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对喂食不同膳食脂肪和蛋白质的大鼠进行甲基汞影响的研究:睾丸类固醇生成酶和血清睾酮水平

An investigation of the effects of methylmercury in rats fed different dietary fats and proteins: testicular steroidogenic enzymes and serum testosterone levels.

作者信息

McVey Mark J, Cooke Gerard M, Curran Ivan H A, Chan Hing Man, Kubow Stan, Lok Eric, Mehta Rekha

机构信息

Toxicology Research Division, Health Products and Foods Branch, Food Directorate, Health Canada, Sir Fredrick G. Banting Research Centre, 2202D1 Tunney's Pasture, Ottawa, ON, Canada K1A 0L2.

出版信息

Food Chem Toxicol. 2008 Jan;46(1):270-9. doi: 10.1016/j.fct.2007.08.004. Epub 2007 Aug 14.

Abstract

Methylmercury (MeHg) is a testicular toxicant causing reduced steroidogenic enzyme activity, reduced serum testosterone (T) and abnormal spermatogenesis in mammals and fowl. It is also known that certain diets can alter androgen metabolism in rats. Previously we have shown that diets used in the current study impact circulating androgen levels and testicular steroidogenic enzyme activities in Sprague Dawley rats in the absence of MeHg. In the present study, we have investigated the impact of imposing an environmental contaminant (MeHg) commonly found in marine mammals and fish onto the rats' dietary intake of different proteins and lipids in order to determine if the different diets could modify MeHg toxicity in rats. Therefore, we examined the effects of MeHg on testicular steroidogenic enzymes and serum testosterone in rats fed diets containing either different protein sources (casein, fishmeal, whey) or different lipid sources (soybean oil, docosahexaenoic acid (DHA), seal oil, fish oil, lard). Male rats 42-45 days of age (18 per group) were assigned to different experimental diets for 28 days after which 6 rats in each group were gavaged daily with 0, 1 or 3 mg/kg body weight (BW)/day MeHg chloride in 5 mM Na(2)CO(3) solution for 14 days while being maintained on their diets. On the 43rd day of dosing, rats were sacrificed and blood plasma and testes frozen (-80 degrees C) until analysis. Microsomal steroidogenic enzyme activities (3beta-HSD, 17-OHase, C-17, 20-lyase, 17beta-HSD) were measured radiometrically. Serum testosterone was determined using ELISA kits. Testis weights were not affected by MeHg. MeHg at 3 mg/kg BW/day caused a reduction (>50%) in the activity of C-17, 20-lyase in all three protein diets and similar reductions in 17-OHase activity were seen in the casein and whey protein fed rats. At 3 mg/kg BW/day, MeHg reduced 17-OHase activity in the DHA diet but had no effect on 3beta-HSD activity and no inhibitory effects on 17beta-HSD activity. MeHg (3 mg/kg BW/day) caused significant reductions in serum T in the whey, soybean oil and fish oil groups. Interestingly, fishmeal protein but not fish oil offered some protection with respect to maintaining steroidogenic enzyme activities and serum T levels in rats dosed with MeHg. In conclusion, these studies show that different lipid diets can alter the toxic effects of MeHg on male rat steroidogenesis in terms of serum testosterone and steroidogenic enzyme activities.

摘要

甲基汞(MeHg)是一种睾丸毒物,可导致哺乳动物和禽类的类固醇生成酶活性降低、血清睾酮(T)水平降低以及精子发生异常。此外,已知某些饮食可改变大鼠体内的雄激素代谢。此前我们已表明,在不存在MeHg的情况下,本研究中使用的饮食会影响Sprague Dawley大鼠的循环雄激素水平和睾丸类固醇生成酶活性。在本研究中,我们研究了将海洋哺乳动物和鱼类中常见的环境污染物(MeHg)施加到大鼠不同蛋白质和脂质的饮食摄入上的影响,以确定不同饮食是否会改变大鼠对MeHg的毒性。因此,我们研究了MeHg对喂食含有不同蛋白质来源(酪蛋白、鱼粉、乳清)或不同脂质来源(大豆油、二十二碳六烯酸(DHA)、海豹油、鱼油、猪油)饮食的大鼠睾丸类固醇生成酶和血清睾酮的影响。42 - 45日龄的雄性大鼠(每组18只)被分配到不同的实验饮食中28天,之后每组6只大鼠每天用5 mM Na₂CO₃溶液配制的0、1或3 mg/kg体重(BW)/天的氯化甲基汞灌胃14天,同时维持其饮食。在给药的第43天,处死大鼠,将血浆和睾丸冷冻(-80℃)直至分析。通过放射性测量法测定微粒体类固醇生成酶活性(3β - HSD、17 - OHase、C - 17,20 - 裂解酶、17β - HSD)。使用ELISA试剂盒测定血清睾酮。睾丸重量不受MeHg影响。3 mg/kg BW/天的MeHg导致所有三种蛋白质饮食中C - 17,20 - 裂解酶活性降低(>50%),在喂食酪蛋白和乳清蛋白的大鼠中,17 - OHase活性也出现类似程度的降低。在3 mg/kg BW/天的剂量下,MeHg降低了DHA饮食中17 - OHase的活性,但对3β - HSD活性没有影响,对17β - HSD活性也没有抑制作用。3 mg/kg BW/天的MeHg导致乳清、大豆油和鱼油组的血清T显著降低。有趣的是,鱼粉蛋白而非鱼油在维持MeHg给药大鼠的类固醇生成酶活性和血清T水平方面提供了一定保护。总之,这些研究表明,不同的脂质饮食在血清睾酮和类固醇生成酶活性方面可以改变MeHg对雄性大鼠类固醇生成的毒性作用。

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