共查询到20条相似文献,搜索用时 0 毫秒
1.
《Journal of trace elements in medicine and biology》2014,28(2):240-246
This work investigated zinc (Zn) and mercury (Hg) effects on oxidative parameters, markers of toxicity and metal levels in different tissues from non-lactating rats (NLR) and lactating rats (LR). Adult NLR and LR received ZnCl2 (27 mg/kg) or saline (0.9%) subcutaneously and after 24 h they received HgCl2 (5 mg/kg) or saline (0.9%). Twenty four hours later, they were sacrificed and the preparation of biological material and biochemical analyses were performed. With respect to oxidative parameters, Hg exposure decreased kidney total SH levels from NLR and LR and hepatic catalase activity (not statistically significant) in NLR. Zinc pre-treatment partly prevented the decrease of kidney total SH levels in LR. Zinc per se increased hepatic non-protein SH levels of NLR and LR. Regarding toxicity markers, Hg exposure inhibited the δ-aminolevulinic acid dehydratase (δ-ALA-D) activity from kidney and liver of NLR, inhibited serum alanine aminotransferase (ALT) activity of LR and increased serum creatinine and urea levels of NLR and LR. Zinc pre-exposure prevented the enzymatic alterations caused by Hg. NLR and LR Hg exposed presented accumulation of mercury in the kidney, liver, blood and urine. Zinc pre-treatment prevented this accumulation partly in NLR liver and blood and completely in LR kidney and liver. These results show that NLR and LR are differently sensitive to HgCl2 and that ZnCl2 showed a promising effect against Hg toxicity. 相似文献
2.
This work investigated the preventive effect of diphenyl diselenide [(PhSe)2] on renal and hepatic toxicity biomarkers and oxidative parameters in adult mice exposed to mercury chloride (HgCl2). Selenium (Se) and mercury (Hg) determination was also carried out. Mice received a daily oral dose of (PhSe)2 (5.0 mg/kg/day) or canola oil for five consecutive days. During the following five days, the animals were treated with a daily subcutaneous dose of HgCl2 (5.0 mg/kg/day) or saline (0.9%). Twenty-four hours after the last HgCl2 administration, the animals were sacrificed and biological material was obtained. Concerning toxicity biomarkers, Hg exposure inhibited blood δ-aminolevulinic acid dehydratase (δ-ALA-D), serum alanine aminotransferase (ALT) activity and also increased serum creatinine levels. (PhSe)2 partially prevented blood δ-ALA-D inhibition and totally prevented the serum creatinine increase. Regarding the oxidative parameters, Hg decreased kidney TBARS levels and increased kidney non-protein thiol levels, while (PhSe)2 pre-treatment partially protected the kidney thiol levels increase. Animals exposed to HgCl2 presented Hg content accumulation in blood, kidney and liver. The (PhSe)2 pre-treatment increased Hg accumulation in kidney and decreased in blood. These results show that (PhSe)2 can be efficient in protecting against these toxic effects presented by this Hg exposure model. 相似文献
3.
Divalent cadmium and mercury ions are capable in vitro of displacement of zinc from metallothionein. This process has now been studied in vivo and ex vivo, using the isolated perfused rat liver system, in order to determine if this process can occur in the intact cell. Rats with normal and elevated (via preinduction with zinc) levels of hepatic zinc thionein were studied. Cd(II) completely displaces zinc from normal levels of metallothionein and on a one-to-one basis from elevated levels of metallothionein, both in vivo and ex vivo. Hg(II) displaces zinc from metallothionein (normal or elevated) rather poorly, as compared with Cd(II), in vivo, probably due to the kidneys preference for absorbing this metal. Ex vivo Hg(II) displaces zinc from metallothionein (normal or elevated) on a one-to-one basis, with considerably more mercury being incorporated into the protein than in vivo. The results of double-label ex vivo experiments using metal and [35S]cysteine (+/- cycloheximide) were consistent with the above experiments, indicating that de novo thionein synthesis was not required for short term incorporation of cadmium and mercury into metallothionein. These data are supportive of the hypothesis that cadmium and mercury incorporation into rat hepatic metallothionein during the first few hours after exposure to these metals can occur primarily by displacement of zinc from preexisting zinc thionein by a process which does not require new protein synthesis. 相似文献
4.
5.
Metallothionein, zinc, and mercury levels in tissues of young rats exposed to zinc and subsequently to mercury 总被引:1,自引:0,他引:1
Several studies have described mercury toxicity and the role of metallothioneins (MT) in the detoxification and regulation of metal homeostasis. However, little data exist on this topic during the specific post-natal developmental phase in young mammals. This developmental phase is particularly important since young animals are more sensitive to toxicants than adults. The objective of this work was to investigate whether MT participates in the mechanism of protection conferred by zinc pre-treatment on the toxic effects induced by mercury in neonate rats. Pups were exposed to ZnCl(2) (5 doses of 27 mg/kg/day, s.c.) and subsequently to HgCl(2) (5 doses of 5 mg/kg/day, s.c.); metal (Zn and Hg) and MT contents were analyzed in the liver, kidney, and blood. MT was induced in the liver and kidney of pups of both Zn-sal and Zn-Hg groups, although the greatest increase was in neonates exposed to Zn only. A direct relationship exists between MT and metals for both hepatic and renal tissues, which indicates that the increase in metal levels occurs in parallel to the increase in MT content. Although the heat-treated cytosolic fraction is rich in MT and metals, higher Zn and Hg contents were detected in the insoluble fraction of all tissues. These results suggest that MT is, at least in part, responsible for preventing Hg accumulation in the liver and blood and decreasing renal toxicity. 相似文献
6.
The developmental alterations in metallothionein (MT) proteins and zinc (Zn) were investigated in brains of two transgenic
strains of mice. MT protein was measured by a cadmium binding assay and Zn by atomic absorption spectrophotometry. MT proteins
were expressed at birth (day 1) both in MT-I overexpressing transgenic mouse (MT-I*) and MT-null (expressing only brain specific
isoform, MT-III) transgenic mouse. MT proteins level (mainly MT-I) in MT-I* was 16.1 Μ-g/g at birth, and thereafter increased
with age to a maximal adult level of 55.3 Μg/g (day 60). Zn level in MT-I* also increased from 8.43 Μg/g (day 1) to 20.7 Μg/g
(day 60) with age. MT protein (MT-III) in MT-null mouse was 9.71 Μg/g at birth and remained relatively unchanged during development.
Zn level in MT-null mouse at birth was 9.46 Μg/g and also remained unchanged during development. The similar alterations in
MT isoforms and Zn in brain during development suggest that MT isoforms may act as a Zn binding protein. 相似文献
7.
The influence of protein deprivation and cystein deficiency on the distribution of methyl mercury between 4 subcellular fractions of liver was studied in 2 rat strains (Wistar, strain R and Sprague-Dawley). Kept on a standard diet, the 2 strains showed a similar distribution pattern, with the highest mercury level found in the cytosol, followed by the mitochondrial, microsomal and nuclei fractions. The protein free diet caused on increase in the total amount of bound mercury in both strains, the greatest increase, being found in livers from strain R rats. The cystein deficient diet, on the other hand, gave rise to diverging results. Whereas the level of mercury bound to the subcellular fractions was increased in livers from strain R rats, it was markedly reduced in livers from Sprague-Dawley rats. 相似文献
8.
9.
Minoru Yoshida Hisayoshi Ohta Youji Yamaguchi Yukio Seki Morihisa Sagi Kentarou Yamazaki Yawara Sumi 《Biological trace element research》1998,63(2):167-175
Samples of liver, renal cortex, and medulla were obtained from 55 forensic autopsies (0- to 95-yr-old Japanese). Metallothionein
(MT) was determined by the Ag-hem or Cd-hem method. Zinc (Zn), copper (Cu), and cadmium (Cd) were determined by atomic absorption
spectrophotometry. The mean levels of MT were 250 μg/g in the liver, and 394 μg/g (cortex) and 191 μg/g (medulla) in the kidney.
Age-dependent changes were observed in both the liver and kidney. In the liver, MT level decreased during infancy and increased
thereafter with age. Similar age-dependent changes in the levels of Zn and Cu were observed. In the kidney cortex, MT level
increased with age, although no correlation was found after middle age. The levels of Cd and Zn also increased with age until
middle age; however, they decreased thereafter. These results suggest that age-dependent changes in renal MT levels are associated
with accumulation of Cd. 相似文献
10.
Rakhi Agarwal S. Raisuddin Shikha Tewari Sudhir K. Goel R. B. Raizada Jai Raj Behari 《Journal of biochemical and molecular toxicology》2010,24(2):123-135
To evaluate the effect of pre‐ or posttreatment of selenium (6 μmol/kg b.w., single intraperitoneal injection) in mercury intoxication, rats were exposed to mercury (12 μmol/kg b.w., single intraperitoneal injection). Exposure to mercury resulted in induced oxidative stress in liver, kidney, and brain tissues. Marked changes in serum biochemical parameters together with alterations in histopathology and an induction in metallothionein‐I and metallothionein‐II mRNA expression in the liver and kidney were observed. Pretreatment with selenium to mercury‐exposed animals had protective effect on the liver, whereas posttreatment had partial protection on restoration of altered oxidative stress parameters. In the kidney, pretreatment with selenium showed partial protection on restoration of altered biochemical parameters, whereas no protection was observed in posttreatment. The pretreatment with selenium resulted in restoration of mercury‐induced metallothionein‐I and metallothionein‐II mRNA expression, which was completely restored in the liver whereas partial restoration was observed in the kidney. Posttreatment with selenium resulted in further induction in metallothionein‐I and metallothionein‐II mRNA expression in the liver and kidney. In the brain, selenium showed partial protection on alerted biochemical parameters. Results indicate that pretreatment with selenium is beneficial in comparison to posttreatment in mercury intoxication. Thus, dietary intake of selenium within safe limit may, therefore, enable us in combating any foreseen effects due to mercury exposure. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:123–135, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20320 相似文献
11.
Krishna Prahlad Maremanda Sabbir Khan Gopabandhu Jena 《Biochemical and biophysical research communications》2014
The role of zinc (Zn) in the protection of germ cells against testicular toxicants has long been elucidated, but the exact molecular mechanisms have not yet been explored. Cyclophosphamide (CP), one of the most commonly used anticancer drugs survived ages of treatment, but the unwanted toxicity limits its clinical usage. The present investigation was aimed to explore the role of Zn and its associated pathways in CP-induced testicular toxicity in S.D. rat. CP was administered in saline 30 mg/kg 5× weekly for 3 weeks (total dose of 450 mg/kg) by i.p. route, while Zn was supplemented by oral route at the doses of 1, 3, 10 mg/kg/day for 3 weeks. CP significantly reduced Zn levels in serum and testes, body and testicular weight, sperm count and motility, spermiogenic cells, plasma testosterone and significantly increased the oxidative stress, sperm head abnormalities, sperm DNA damage with decreased chromatin and acrosome integrity; while Zn supplementation ameliorated the same. The present results demonstrated that Zn supplementation protected against CP-induced testicular damages by modulating metallothionein (MT), tesmin and Nrf2 associated pathways. Thus Zn supplementation during anticancer therapy might be potentially beneficial in reducing the off target effects associated with oxidative stress. 相似文献
12.
Caroline B. Houghton M. George Cherian 《Journal of biochemical and molecular toxicology》1991,6(3):221-228
The effects of alterations in sulfur metabolism on hepatic and renal metallothionein and glutathione metabolism were studied in the adult rat using inhibition of two enzymes of these pathways, hepatic cystathionase and renal gamma-glutamyl transpeptidase. Rats were fed a diet containing both methionine (0.66%) and cystine (0.20%) for 1 week before receiving three consecutive daily intraperitoneal injections of propargylglycine, a selective cystathionase inhibitor, at various doses (2.5–375 μmol/kg). When hepatic cystathionase was inhibited greater than 90% (≥50 μmol propargylglycine/kg), renal and hepatic metallothionein and hepatic glutathione were unaltered except at the highest dose. On the other hand, renal glutathione was increased twofold with a concomitant decrease in renal gamma-glutamyl transpeptidase activity (50% of control). In another experiment, when renal gamma-glutamyl transpeptidase was inhibited greater than 90% with three consecutive daily injections of acivicin, a selective gamma-glutamyl transpeptidase inhibitor (10 mg/kg IP), renal glutathione content was unaltered while hepatic glutathione was decreased. Renal and hepatic metallothionein were not changed. Thus, the cysteine pools for metallothionein and glutathione appear unrelated under the present experimental conditions. In addition, following either propargylglycine or acivicin injections, renal and hepatic glutathione pools appear to be altered differently. These results suggest that renal glutathione may be preferentially maintained even when hepatic glutathione is decreased. 相似文献
13.
Zuotai (mainly β-HgS) and Zhusha (also called as cinnabar, mainly α-HgS) are used in traditional medicines in combination with herbs or even drugs in the treatment of various disorders, while mercury chloride (HgCl2) and methylmercury (MeHg) do not have known medical values but are highly toxic. This study aimed to compare the effects of mercury sulfides with HgCl2 and MeHg on hepatic drug processing gene expression. Mice were orally administrated with Zuotai (β-HgS, 30 mg/kg), α-HgS (HgS, 30 mg/kg), HgCl2 (33.6 mg/kg), or MeHg (3.1 mg/kg) for 7 days, and the expression of genes related to phase-1 drug metabolism (P450), phase-2 conjugation, and phase-3 (transporters) genes were examined. The mercurials at the dose and duration used in the study did not have significant effects on the expression of cytochrome P450 1–4 family genes and the corresponding nuclear receptors, except for a slight increase in PPARα and Cyp4a10 by HgCl2. The expressions of UDP-glucuronosyltransferase and sulfotransferase were increased by HgCl2 and MeHg, but not by Zuotai and HgS. HgCl2 decreased the expression of organic anion transporter (Oatp1a1), but increased Oatp1a4. Both HgCl2 and MeHg increased the expression of multidrug resistance-associated protein genes (Mrp1, Mrp2, Mrp3, and Mrp4). Zuotai and HgS had little effects on these transporter genes. In conclusion, Zuotai and HgS are different from HgCl2 and MeHg in hepatic drug processing gene expression; suggesting that chemical forms of mercury not only affect their disposition and toxicity, but also affect their effects on the expression of hepatic drug processing genes. 相似文献
14.
Nagamine T Kusakabe T Takada H Nakazato K Sakai T Oikawa M Satoh T Arakawa K 《Cytokine》2006,34(5-6):312-319
We evaluated the changes of metallothionein induction and cellular zinc distribution in HepG2 cells by interferonbeta treatment. Immunohistochemical staining of metallothionein was observed in the cytoplasm and nuclei of hepatocytes; which was observed predominantly in the cells treated with interferon and zinc compared to those with zinc alone, interferon alone or the no-treated control. The cellular zinc level was higher in order of the interferon- and zinc-treated cells, the zinc-alone-treated cells, and the interferon-alone-treated cells. Flow cytometry showed that S-phase population increased in interferon-alone-treated cells and interferon- and zinc-treated cells, but not in zinc-alone-treated ones. Cellular elemental distribution was analyzed using in-air micro-particle induced X-ray emission. In zinc-alone-treated sample, X-ray spectra showed good consistency between the enhanced cellular zinc distribution and the phosphorous map. Localizations of bromine followed by interferon treatment were found accompanying a spatial correlation with the phosphorous map. The samples treated with interferon and zinc showed the marked accumulation of zinc and bromine. Discrete bromine accumulation sites were clearly visible with a strong spatial correlation followed by zinc accumulation. These findings suggest that interferonbeta in combination with zinc predominantly induces metallothionein expression in HepG2 cells. In addition, interferonbeta may promote the translocation of metallothionein-bound zinc from cytoplasm to S-phase nuclei. 相似文献
15.
A. M. Rofe J. C. Philcox D. R. Haynes M. W. Whitehouse P. Coyle 《Biological trace element research》1992,34(3):237-248
The early changes in hepatic metallothionein (MT) and plasma zinc (Zn), copper (Cu), and iron (Fe) were investigated during
the induction of adjuvant (AJ) arthritis in rats in conjunction with cyclosporin (CSA) treatment. Plasma Zn decreased after
AJ injection (60% of control values at 8 h), and this was associated with a 4.5-fold increase in hepatic MT at 8 h. Plasma
Zn was lowest at 16 h (40% of control), whereas hepatic MT concentrations increased to a maximum of 20-fold at 16 h. Changes
in plasma Fe paralleled those of Zn, whereas plasma Cu levels were increased. Plasma metal and hepatic MT concentrations returned
toward normal from d 1–7. At d 14, when marked paw swelling was apparent, hepatic MT and plasma Cu were again increased and
plasma Zn decreased.
Administration of CsA decreased MT induction in rats injected with AJ and also caused a marked recovery in plasma Zn and Fe
levels. These changes were small but significant even in the early stages (up to 24 h) after AJ injection and were followed
by a sustained improvement in all parameters, corresponding to the nonappearance of clinical arthropathy in CsA-treated rats.
TNF-α and IL-6 production by peritoneal macrophages isolated from AJ-injected rats was significantly decreased by CsA treatment
at d 7 and 14. The inhibition of hepatic MT induction during acute and chronic inflammation by cyclosporin emphasizes the
role of the immune system in altered metal homeostasis in inflammation. 相似文献
16.
Regional distribution of metallothionein, zinc, and copper in the brain of different strains of rats 总被引:4,自引:0,他引:4
The regional brain distribution of metallothionein (MT), zinc, and copper in the brain was determined in nine anatomical regions
(olfactory bulb, cortex, corpus striatum, hippocampus, thalamus plus hypothalamus, pons plus medulla oblongata, cerebellum,
midbrain, and white matter) and was compared between two different strains of rat (Sprague-Dawley [SD] and Lewis). No significant
difference was observed in the whole-brain MT level between the two strains (17.8 ± 3.4 μg/g in SD rats and 20.3 ± 2.3 μg/g
in Lewis rats). In SD rats, however, MT was more highly expressed in the white matter than in the other regions studied. In
contrast, MT concentration was highest in the cortex and lowest in the olfactory bulb in Lewis rats. The MT levels in the
cortex, corpus striatum, hippocampus, and thalamus plus hypothalamus were significantly lower in SD rats than in Lewis rats.
In both strains, the olfactory bulb contained markedly higher levels of both zinc and copper than the other regions (27.9
±6.8 μg/g zinc in SD rats and 27.6 ± 6.9 μg/g zinc in Lewis rats, and 5.2 ± 1.5 μg/g copper in SD rats and 11.1 ± 4.8 μg/g
copper in Lewis rats). The next high-est zinc levels were seen in the hippocampus, whereas the next highest copper levels
were in the corpus striatum in both SD and Lewis rats. The high levels of zinc and copper in the olfactory bulb were not accompanied
by concomitant high MT concentrations. These results indicate that the strain of rat as well as the anatomical brain region
should be taken into account in MT and metal distribution studies. However, the highest concentrations of zinc and copper
in olfactory bulb were common to both SD and Lewis rats. The discrepancy between MT and the metal levels in olfactory bulb
suggests a role for other proteins in addition to MT in the homeostatic control of zinc and copper. 相似文献
17.
Brandão R Santos FW Farina M Zeni G Bohrer D Rocha JB Nogueira CW 《Cell biology and toxicology》2006,22(6):429-438
Acute effects of mercury on mouse blood, kidneys, and liver were evaluated. Mice received a single dose of mercuric chloride
(HgCl2, 4.6 mg/kg, subcutaneously) for three consecutive days. We investigated the possible beneficial effects of antioxidant therapy
(N-acetylcysteine (NAC) and diphenyl diselenide (PhSe)2) compared with the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), an effective chelating agent in HgCl2 exposure in mice. We also verified whether metallothionein (MT) induction might be involved in a possible mechanism of protection
against HgCl2 poisoning and whether different treatments would modify MT levels and other toxicological parameters. The results demonstrated
that HgCl2 exposure significantly inhibited δ-aminolevulinate dehydratase (δ-ALA-D) activity in liver and only DMPS treatment prevented
the inhibitory effect. Mercuric chloride caused an increase in renal non-protein thiol groups (NPSH) and none of the treatments
modified renal NPSH levels. Urea concentration was increased after HgCl2 exposure. NAC plus (PhSe)2 was partially effective in protecting against the effects of mercury. DMPS and (PhSe)2 were effective in restoring the increment in urea concentration caused by mercury. Thiobarbituric acid-reactive substances
(TBARS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities and ascorbic acid levels were not
modified after mercury exposure. Mercuric chloride poisoning caused an increase in hepatic and renal MT levels and antioxidant
treatments did not modify this parameter. Our data indicated a lack of therapeutic effect of the antioxidants tested. 相似文献
18.
AimThe potential effects of heavy metals on non-alcoholic fatty liver disease (NAFLD) remain unknown. We investigated the sex-specific relationships of blood lead (BPb), mercury (BHg), and cadmium (BCd) levels with hepatic steatosis (HS) and fibrosis (HF).MethodWe included 4420 participants from the 2016–2017 Korea National Health and Nutrition Examination Survey. High-risk alcoholics and patients with chronic hepatitis B or C infections or liver cirrhosis were excluded. We calculated the hepatic steatosis index (HSI) and fibrosis-4 index (FIB-4) values; we defined the presence of HS and HF as an HSI ≥ 36 and FIB-4 score >2.67, respectively. We adjusted for age, smoking and alcohol consumption statuses, hypertension, obesity, diabetes, hypertriglyceridemia, and BPb, BHg, and BCd levels.ResultIn males (n = 1860), the HSI was correlated negatively with the BPb level and positively with the BHg level (both p < 0.01). The FIB-4 score was correlated positively with the BPb and BCd levels (both p < 0.01). In females (n = 2560), the HSI and FIB-4 score were correlated positively with the BPb, BHg, and BCd levels (all p < 0.01). After adjustments, the BHg level increased the risk of HS in both males (OR = 1.065, p = 0.003) and females (OR = 1.061, p = 0.048), and the BCd level increased the risk of HF in females (OR = 1.668, p = 0.012).ConclusionBlood heavy metal levels were generally correlated positively with the HSI and FIB4 score, more so in females than males. The BHg level was associated with HS in males and females, and the BCd level was associated with HF in females. Further studies on NAFLD progression according to heavy metal status and sex are warranted. 相似文献
19.
The changes of heavy metal and metallothionein distribution in testis induced by cadmium exposure 总被引:1,自引:0,他引:1
Takahiko Kusakabe Katsuyuki Nakajima Keiji Suzuki Kyoumi Nakazato Hisashi Takada Takahiro Satoh Masakazu Oikawa Kenji Kobayashi Hiroshi Koyama Kazuo Arakawa Takeaki Nagamine 《Biometals》2008,21(1):71-81
Cadmium (Cd) is known to cause various disorders in the testis, and metallothionein (MT) is known as a protein, which has
a detoxification function for heavy metals. However, the changes of Fe, Cu, and Zn distribution in the testis induced by Cd
exposure have not been well examined. Moreover, only a few studies have been reported on the localization of MT after Cd exposure.
In this study, we have investigated the changes of Fe, Cu, and Zn distribution in Cd-exposed testis by a newly developed in
air micro-Particle Induced X-ray Emission (PIXE) method. Also, we examined the distribution of MT expression in testis. In
the testis of Cd-treated rats with significant increases of lipid peroxidation, the sertoli cell tight junction was damaged
by Cd exposure, resulting from disintegration of the blood testis barrier (BTB). Evaluation by in air micro-PIXE method revealed
that Cd and Fe distribution were increased in the interstitial tissues and seminiferous tubules. The histological findings
indicated that the testicular tissue damage was advanced, which may have been caused by Fe flowing into seminiferous tubules
followed by disintegration of the BTB. As a result, Fe was considered to enhance the tissue damage caused by Cd exposure.
MT was detected in spermatogonia, spermatocytes, and Sertoli’s cells in the testis of Cd-treated rats, but was not detected
in interstitial tissues. These results suggested that MT was induced by Cd in spermatogonia, spermatocytes, and Sertoli’s
cells, and was involved in the resistance to tissue damage induced by Cd. 相似文献
20.
Lange A Ausseil O Segner H 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2002,131(3):231-243
The objective of this study was to assess the effects of Cd and Zn exposure of rainbow trout (Oncorhynchus mykiss) on (a) hepatic glutathione (GSH) levels; and (b) hepatic and branchial metallothionein (MT) mRNA expression. Juvenile rainbow trout were exposed to waterborne Cd (nominal concentrations: 1.5 or 10 microg Cd l(-1)), Zn (150 or 1000 microg Zn l(-1)) or Cd/Zn mixtures (1.5 microg Cd l(-1) with 200 microg Zn l(-1) or 10 microg Cd l(-1) with 1000 microg Zn l(-1)). After 14 and 28 days of treatment, hepatic concentrations of total glutathione, oxidized glutathione (GSSG) and cysteine were determined by means of fluorometric high performance liquid chromatography (HPLC). Branchial and hepatic expression of MT mRNA was measured by means of semi-quantitative RT-PCR. Exposure of trout to Zn did not result in significantly elevated tissue levels of Zn, whereas Cd accumulation factors changed significantly with time and concentration. Despite of the absence of Zn accumulation, hepatic GSH but not MT mRNA levels were significantly altered in Zn-exposed fish. Cd, on the contrary, affected mainly the MT response but not GSH. Also tissue specific differences in the regulation of the two thiol pools were expressed. The thiol response after exposure to metal mixtures could not be explained by simple addition of the effects of the individual metals. The results indicate that cellular thiol pools show different reaction patterns with respect to specific metals and metal mixtures. Under conditions of long-term, low dose metal exposure, the function of GSH appears to go beyond that of a transitory, first line defense. 相似文献