Carp Kidney Research Articles

Effect of dietary glutamine on growth performance, non-specific immunity, expression of cytokine genes, phosphorylation of target of rapamycin (TOR), and anti-oxidative system in spleen and head kidney of Jian carp (Cyprinus carpio var. Jian).

This study was designed to investigate the effects of dietary glutamine on the growth performance, cytokines, target of rapamycin (TOR), and antioxidant-related parameters in the spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian). Fish were fed the basal (control) and glutamine-supplemented (12.0gglutaminekg(-1) diet) diets for 6weeks. Results indicated that the dietary glutamine supplementation improved the growth performance, spleen protein content, serum complement 3 content, and lysozyme activity in fish. In the spleen, glutamine down-regulated the expression of the interleukin 1 and interleukin 10 genes, and increased the level of phosphorylation of TOR protein. In the head kidney, glutamine down-regulated the tumor necrosis factor α and interleukin 10 gene expressions, phosphorylated and total TOR protein levels, while up-regulated the transforming growth factor β2 gene expression. Furthermore, the protein carbonyl content was decreased in the spleen of fish fed glutamine-supplemented diet; conversely, the anti-hydroxyl radical capacity and glutathione content in the spleen were increased by glutamine. However, diet supplemented with glutamine did not affect the lipid peroxidation, anti-superoxide anion capacity, and antioxidant enzyme activities in the spleen. Moreover, all of these antioxidant parameters in the head kidney were not affected by glutamine. Results from the present experiment showed the importance of dietary supplementation of glutamine in benefaction of the growth performance and several components of the innate immune system, and the deferential role in cytokine gene expression, TOR kinase activity, and antioxidant status between the spleen and head kidney of juvenile Jian carp.

Proteomic identification and characterization of Ctenopharyngodon idella tumor necrosis factor receptor-associated protein 1 (CiTrap1): An anti-apoptosis factor upregulated by grass carp reovirus infection

Human tumor necrosis factor receptor-associated protein 1 (Trap1) is a mitochondrial protein identical to heat shock protein 75 (HSP75) that plays an important role in protecting cells from oxidative stress and apoptosis. In this study, grass carp (Ctenopharyngodon idella) tumor necrosis factor receptor-associated protein 1 (designated as CiTrap1) was identified through two-dimensional electrophoresis (2-DE) analysis and its pattern of expression was investigated in grass carp kidney (CIK) cells infected with grass carp reovirus (GCRV). The full length cDNA of CiTrap1 contained an opening reading frame of 2157 bp that encoded a peptide of 718 amino acids. Phylogenetic analyses indicated that the CiTrap1 shared 87% identity with its homologue from zebrafish (Danio rerio). The transcriptional level of CiTrap1 in CIK cells was upregulated post virus infection as well as poly (I: C) stimulation. Following virus infection, grass carp PTEN-induced putative kinase 1 (PINK1) and Sorcin, whose coding proteins interact with Trap1 in human, were simultaneously upregulated with CiTrap1. Typical characteristics of apoptosis were observed in CIK cells infected with GCRV by DAPI staining, DNA ladder electrophoresis, TUNEL assay and Annexin Ⅴ labeling. RNAi-mediated silencing of CiTrap1 in CIK cells resulted in the increased rate of virus-induced apoptotic cells. The results of this study suggest that CiTrap1 is involved in the host's innate immune response to viral infection possibly through protecting infected cells from apoptosis.

Effects of atrazine and chlorpyrifos on oxidative stress-induced autophagy in the immune organs of common carp (Cyprinus carpio L.)

Atrazine (ATR) and chlorpyrifos (CPF) are the most common agrochemical in the freshwater ecosystems of the world. This study assessed the effects of ATR (4.28, 42.8 and 428 μg/L), CPF (1.16, 11.6 and 116 μg/L) and combined ATR/CPF (1.13, 11.3 and 113 μg/L) on common carp head kidneys and spleens following 40 d exposure and 40 d recovery treatments. Nitric oxide (NO) content, activities of anti hydroxyl radical (AHR), anti superoxide anion (ASA), peroxidase (POD) and inducible nitric oxide synthase (iNOS), and the mRNA levels of the autophagy genes (LC3-II, dynein, TOR) were determined. The results indicate that the antioxidant enzyme (AHR, ASA, POD and iNOS) activities and NO content in the head kidney and spleen of the common carp increased significantly after a 40 d exposure to ATR and CPF alone or in combination. The mRNA levels of LC3-II and dynein in common carp increased significantly after exposure to ATR and CPF alone, or in combination. Moreover, the mRNA levels of LC3-II and dynein decreased significantly after a 40-d recovery. However, the mRNA levels of TOR gene for all decreased significantly at the end of the exposure and the recovery. To our knowledge, this is the first study to report the oxidative stress-induced autophagic effects in the common carp by exposure to ATR, CPF and the ATR/CPF combination. The information presented in the present study may be helpful to understanding the mechanisms of autophagy induced by ATR, CPF and the ATR/CPF combination in fish.

The in vitro immune modulatory effect of bisphenol A on fish macrophages via estrogen receptor α and nuclear factor-κB signaling.

Bisphenol A (BPA) is a well-known environmental endocrine-disrupting chemical. Employing primary macrophages from head kidney of red common carp (Cyprinus carpio), the present study aimed to evaluate the immune modulatory effect of BPA and to explore its potential action mechanism associated with estrogen receptor (ER) and nuclear factor-κB (NF-κB) pathways. A dynamic response process was observed in macrophages upon various concentrations of BPA exposure, which significantly enhanced the antibacterial activity of macrophages at 0.1, 1, or 10 μg/L, but instead induced the apoptosis at 100, 1000, and 10,000 μg/L. A potential pro-inflammatory effect of BPA exposure was suggested, judging from the increased production of nitrite oxide and reactive oxygen species (ROS), the induction of interleukin-1β mRNA and protein, as well as NF-κB and other NF-κB-associated immune gene expression. Following BPA coexposure with the ER or NF-κB antagonist, the induction of ROS, ERα, and NF-κB-associated immune gene expression was significantly inhibited, implying interaction between those two pathways. This study thus indicated that low doses of BPA exposure alone could significantly disturb the immune response of fish primary macrophages in vitro, and for the first time revealed the synergistic action of ERα and NF-κB transcription factors in the BPA effect.

Alternations in the liver enzymatic activity of Common carp, Cyprinus carpio in response to parasites, Dactylogyrus spp. and Gyrodactylus spp.

The present study was carried out to investigate the effects of parasites, monogenea, Dactylogyrus spp. and Gyrodactylus spp. on some enzymatic and biochemical components of liver in healthy and infected common carp, Cyprinus carpio. For this purpose, 10 healthy and 10 infected fish were collected from farm. The blood samples were taken and after separation of serum, the values of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) enzymes activities as well as Creatinine and Urea were measured. Based on obtained results, the values of AST, ALT enzymes activities as well as Creatinine and Urea were higher in the infected fish compared to non-infected fish. In conclusion; our results reveals that infection with external parasites, Dactylogyrus spp. and Gyrodactylus spp. can causes some dysfunctions in liver and kidney of common carp.

Assessment of pesticide residues and gene expression in common carp exposed to atrazine and chlorpyrifos: Health risk assessments

This study assessed the impacts of atrazine (ATR), chlorpyrifos (CPF) and combined ATR/CPF exposure on the kidney of common carp (Cyprinus carpio L.). The carp were sampled after a 40-d exposure to CPF and ATR, individually or in combination, followed by a 40-d recovery to measure the expression levels of heat shock proteins genes (HSP60, HSP70 and HSP90) and pesticide residues in the kidney tissue. The results revealed that the mRNA and protein levels of HSP60, HSP70 and HSP90 were induced in the kidney of common carp by ATR, CPF, and ATR/CPF mixture. The accumulated amounts of ATR, CPF, and their metabolites in the kidney tissues exhibited dose-dependency. These results exhibited that increasing concentration of ATR and CPF in the environment causes considerable stress for common carp, suggesting that the expression levels of HSP60, HSP70 and HSP90 may act as potential biomarkers for assessing the environmental ATR and CPF risk for carp.

Experimental studies on the effect of cadmium chloride, zinc acetate, their mixture and the mitigation with vitamin C supplementation on hatchability, size and quality of newly hatched larvae of common carp, Cyprinus carpio

The present results show that the fertilization and hatching rates, as well as the development of the embryos of common carp are adversely affected by heavy metal pollution. The degree of this effect depends on the duration and the concentration of the heavy metal used. Malformation of the yolk sac and curvature in the abdominal region were also observed throughout this study. No statistical difference was recorded between the polluted group which was supplemented with vitamin C (300mg/kg of dry feed), and the control group (P<0.05). The newly hatched larvae showed severe body malformation, and they were not able to swim or feed. Other organs such as the kidneys and livers were also affected. The most important changes in the kidneys of common carp were glomerular expansion and the reduction of Bowman’s space. No abnormalities or alterations were observed in the livers of the control fish. However, the main alterations were observed in the liver of treated fish with cadmium chloride that were either single or mixed with zinc acetate. The most important changes in the livers of common carp were hypertrophy nucleus and vacuolation in cytoplasm. Addition of vitamin C with dry feed showed an improvement in the tissues of livers and kidneys of polluted fish.

Cellular activation, expression analysis and functional characterization of grass carp IκBα: Evidence for its involvement in fish NF-κB signaling pathway

IκBα is a well-known member of the inhibitors of kappa B (IκB) family that controls NF-κB signaling by blocking NF-κB translocation from cytoplasm to nucleus. In the present study, an IκBα homologue was identified from grass carp (gcIκBα), showing the structural characteristics of IκB family. Moreover, mRNA expression of this molecule in grass carp periphery blood lymphocytes (PBLs) was enhanced significantly by both LPS and PHA in a time- and dose-dependent manner, indicating the involvement of gcIκBα in fish immune response. Further analysis demonstrated that LPS but not PHA induced gcIκBα phosphorylation and protein degradation in PBLs, implying different signaling pathways mediated by LPS and PHA in gcIκBα expression regulation in grass carp PBLs. In particular, the time-dependent oscillation of gcIκBα phosphorylation and total protein levels induced by LPS is in accordance with the characteristics of mammalian IκBα phosphorylation followed by protein degradation during NF-κB activation. In support of this notion, overexpression of gcIκBα was able to block both basal and LPS-stimulated NF-κB activity in grass carp kidney cell line, indicating the negatively regulatory role of gcIκBα in NF-κB activity as seen in mammals. Therefore, our results not only reveal a dynamic variation of NF-κB activity based on the activation and expression of IκBα for the first time, but also provide the direct evidence for the involvement of IκBα in NF-κB signaling in fish immune cells.

Immunological and histopathological responses of the kidney of common carp (Cyprinus carpio L.) sublethally exposed to glyphosate

Glyphosate is a broad-spectrum herbicide frequently used world widely in agricultural and non-agricultural areas to control unwanted plants. Health risk of chronic and subchronic exposure of glyphosate on animals and humans has received increasing attention in recent years. The aim of this study was to evaluate the effects of glyphosate on the immunoglobulin M (IgM), complement C3 (C3), and lysozyme (LYZ) in the kidney of common carp exposed to 52.08 or 104.15mgL−1 of glyphosate for 168h. The results showed that the transcriptions of IgM, C3, or LYZ were altered due to glyphosate-exposure, for example, IgM and C3 initially increased at 24h later it decreased (except for a increase of C3 in higher dose group at 24h) while the expression of G-type LYZ were not affected at 24h, then increased at 72h, but decreased at the end of test, however C-type LYZ expression was initially up-regulated (24–72h) but down-regulated at the end of exposure (168h). However, glyphosate-exposure generally decreased the contents of IgM and C3 or inhibited LYZ activity in the kidney of common carp. In addition, glyphosate-exposure also caused remarkable histopathological damage, mainly including vacuolization of the renal parenchyma and intumescence of the renal tubule in fish kidney. The results of this study indicate that glyphosate causes immunotoxicity on common carp via suppressing the expressions of IgM, C3, and LYZ and also via damaging the fish kidney.

Molecular cloning and expression analysis of the Ajuba gene of grass carp (Ctenopharyngodon idella) involved in cellular response to viral infection

Ajuba belongs to the LIM domain proteins, which are involved in the assembly of the extracellular matrix and, along with associated proteins, regulate target genes that connect the extracellular matrix and the cytoskeleton. In the present study, we characterized the entire cDNA sequence of the Ajuba gene from grass carp (gcAjuba). The gcAjuba cDNA contained an open reading frame (ORF) of 2121 bp encoding a polypeptide of 706 amino acids with an estimated molecular mass of 75.966 kDa and three LIM domains in the C-terminal. The transcriptional level of gcAjuba was significantly up-regulated following the stimulation of virus in vitro. Sub-cellular location of gcAjuba and GCRV-JX01 NS26 proteins did not overlap in the cytoplasm and no direct interaction between gcAjuba and the protein NS26 was detected by co-immunoprecipitation (CO-IP) test in grass carp kidney cells. Based on these results, the gcAjuba is determined to be an immediately inducible gene responding to viral infection and in vivo association of gcAjuba with NS26 could not be confirmed, which has been suggested by yeast two-hybrid assay in previous report.

Expression of ERK and p-ERK proteins of ERK signaling pathway in the kidneys of fluoride-exposed carp (Cyprinus carpio)

Chronic exposure to fluoride can result in a variety of adverse effects in fish. Previously we indicated that high fluoride caused damage and apoptosis in the kidneys of the common carp, Cyprinus carpio. In this study, the effects of fluoride on the expression and localization of ERK and p-ERK proteins in the ERK signaling pathway were determined using Western blotting and immunohistochemical methods in the kidneys of carp exposed to 0, 40, 80, 120mg/L fluoride, respectively. Western blotting analysis found that compared with the controls, the levels of ERK1 and ERK2 proteins were relatively unchanged in fluoride-exposed fish, while p-ERK1 and p-ERK2 protein levels decreased significantly with the increased fluoride concentrations. The immunohistochemical analysis found the proteins of ERK and p-ERK were predominantly localized in the cytoplasm of epithelial cells in the renal tubules of C. carpio. Compared with the control group, the levels of ERK protein were relatively constant, yet the levels of p-ERK protein and p-ERK/ERK ratio were reduced with fluoride exposure dose. These findings indicate that the renal damage in carp exposed to fluoride is mediated via the ERK pathway. Fluoride exposure could inactivate ERK, inhibit the expression of p-ERK protein, and induce renal damage in C. carpio.

Transcription alteration of immunologic parameters and histopathological damage in common carp (Cyprinus carpio L.) caused by paraquat.

The toxic effects of paraquat (PQ) on the transcription of immunoglobulin M (IgM), complement C3 (C3), and lysozyme (LYZ) and the histopathological alteration of the liver, kidney, and spleen of common carp were evaluated by subacute exposure to 1.596 or 3.192 mg/L of PQ for 7 days. The results demonstrated that PQ exposure altered the transcription of IgM, C3, and LYZ. For example, IgM and C3 expression was generally downregulated, but LYZ was either down- or upregulated, suggesting that PQ may disturb the function of the fish immune system. The results of the histopathological examination revealed that the liver, kidney, and spleen of PQ-treated fish were injured. These injuries included cellular swelling, intracytoplasmic vacuolization, nucleus distortion, and pycnosis in the liver and spleen, and vacuolization of the renal parenchyma and intumescence of the renal tubule in the kidney. This finding indicates that PQ causes toxicity in common carp.

Pro- and anti-inflammatory cytokine expression in immune organs of the common carp exposed to atrazine and chlorpyrifos

Atrazine (ATR) and chlorpyrifos (CPF) are toxic and subject to long-term in vivo accumulation in different aquatic species throughout the world. The purpose of the present study was to examine the effect of ATR, CPF and combined ATR/CPF exposure on cytokines in the head kidney and spleen of common carp (Cyprinus carpio L.). The carp were sampled after a 40-d exposure to CPF and ATR, individually or in combination, followed by a 40-d recovery to measure the mRNA expression of IL-6fam (IL-6), IL-8, TNF-α, IL-10 and TGF-β1 (TGF-β) in the head kidney and spleen tissues. These results showed that the expression of cytokines IL-6, IL-8 and TNF-α in the head kidney and spleen was upregulated following ATR, CPF and mixed ATR/CPF exposure compared with the control group. The expression of IL-10 and TGF-β mRNA was significantly inhibited in both head kidney and spleen of carp exposed to ATR, CPF and the ATR/CPF mixture. The results suggested that long-term exposure of ATR, CPF and the ATR/CPF mixture in aquatic environments can induce the dysregulation of pro-/anti-inflammatory cytokine expression. The information regarding the effects of ATR and CPF on cytokine mRNA expression generated in this study will be important information for pesticides toxicology evaluation.

Effects of atrazine and chlorpyrifos on DNA methylation in the liver, kidney and gill of the common carp (Cyprinus carpio L.)

Pesticide exposure has repeatedly been associated with cancers, although the molecular mechanisms behind this association are largely undetermined. Abnormal DNA methylation plays a key role in the process of some disease. However, little was known about the effect of pesticides on DNA methylation in the common carp. In this study, we investigated the mRNA levels of DNA methyltransferases (DNMTs) and methyl-CpG-binding protein DNA-binding domain protein 2 (MBD2) as well as the DNA methylation levels in the liver, kidney and gill of the common carp (Cyprinus carpio L.) after 40-d exposure to atrazine (ATR) and chlorpyrifos (CPF) alone or in combination, and a 40-d recovery period. Juvenile common carp were exposed to various concentrations of ATR (at concentrations of 4.28, 42.8 and 428μg/L), CPF (1.16, 11.6 and 116μg/L), and an ATR/CPF mixture (at concentrations of 1.13, 11.3 and 113μg/L). The results revealed that the levels of genomic DNA methylation decreased in all tissues after 40d of exposure to ATR and CPF either individually or in combination. Moreover, the mRNA expression of DNMTs was down-regulated in all treatment groups. In contrast, the mRNA expression of MBD2 was up-regulated. These results demonstrated that long-term exposure to ATR, CPF and ATR/CPF mixtures could disrupt genomic DNA. It might imply that DNA methylation is involved in the toxicity caused by ATR and CPF in the common carp.

Draft Genome Sequence of Aeromonas hydrophila Strain Ae34, Isolated from a Septicemic and Moribund Koi Carp (Cyprinus carpio koi), a Freshwater Aquarium Fish.

Aeromonas hydrophila is an important opportunistic pathogen that infects a variety of aquatic and terrestrial animals, including humans. We report here the draft genome sequence of A. hydrophila Ae34, a multidrug-resistant isolate from the kidney of a moribund koi carp (Ciprinus carpio koi) with signs of hemorrhagic septicemia.

The effect of arsenic on some antioxidant enzyme activities and lipid peroxidation in various tissues of mirror carp (Cyprinus carpio carpio).

The effect of arsenic bioaccumulation in liver, kidney, skin, muscle, and intestinal tissues of mirror carp (Cyprinus carpio carpio) was investigated on lipid peroxidation and certain antioxidant enzyme activities. In this study, three aquarium groups were formed from mirror carp: control group, 0.5-, and 1-mg/L arsenic concentrations. The fish were dissected after 1 month. Arsenic bioaccumulation, malondialdehyde (MDA) levels, catalase (CAT), and superoxide dismutase (SOD) enzyme activities were determined in the tissues. Results showed that arsenic was accumulated in liver, kidney, muscle, skin, and intestinal tissues. As the final product of lipid peroxidation, MDA levels were determined to have increased in all tissues with the exception of muscle. On the other hand, CAT and SOD enzyme activities in the fish tissues were decreased as compared to the control group. In the muscle tissue, differences were observed in the enzyme activities depending on arsenic concentration. Considering the increases in enzyme inhibition and MDA levels, liver was observed to be the main tissue affected in response to the arsenic toxicity.

Profenofos-induced effect on esterase activity and protein content in liver, kidney, brain, blood, and muscles in Indian major carp

The objective of this study was to determine the biochemical alterations induced by acute exposure to profenofos (OP) on esterase activity in liver, kidney, brain, blood, and muscles of Catla catla, Labeo rohita, and Cirrhinus mrigala fingerlings. Pesticides were applied to fingerlings that had been grown under optimized standard conditions maintained in a static bioassay system. The fingerlings of Catla catla, Labeo rohita, and Cirrhinus mrigala were exposed to three sub-lethal concentrations of profenofos 0.038, 0.019, 0.012; 0.06, 0.03, 0.02; and 0.041, 0.02, 0.013, respectively, for 60 days. The activity of cholinesterases (acetylcholinesterase and butyrylcholinesterase) was significantly inhibited at concentrations of profenofos. Exposure to profenofos affected the functions of these organs, including metabolism and neurotransmission to varying extent at different exposure concentrations. Data indicated that profenofos produced greater inhibition of hepatic cholinesterases compared to other tissues.

Effect of choline on antioxidant defenses and gene expressions of Nrf2 signaling molecule in the spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian)

The present work evaluates the effects of various levels of dietary choline on antioxidant defenses and gene expressions of Nrf2 signaling molecule in spleen and head kidney of juvenile Jian carp (Cyprinus carpio var. Jian). Fish were fed with six different experimental diets containing graded levels of choline at 165 (choline-deficient control), 310, 607, 896, 1167 and 1820 mg kg−1 diet for 65 days. At the end of the feeding trail, fish were challenged with Aeromonas hydrophila and mortalities were recorded over 17 days. Dietary choline significantly decreased malondialdehyde and protein carbonyl contents in spleen and head kidney. However, anti-superoxide anion and anti-hydroxyl radical activities in spleen and head kidney also decreased. Interestingly, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) in spleen, GPx activity in head kidney, and glutathione contents in spleen and head kidney were decreased with increase of dietary choline levels up to a certain point, whereas, activities of SOD, GST and GR in head kidney showed no significantly differences among groups. Similarly, expression levels of CuZnSOD, MnSOD, CAT, GPx1a, GPx1b and GR gene in spleen and head kidney were significantly lower in group with choline level of 607 mg kg−1 diet than those in the choline-deficient group. The relative gene expressions of Nrf2 in head kidney and Keap1a in spleen and head kidney were decreased with increasing of dietary choline up to a certain point. However, the relative gene expression of Nrf2 in spleen were not significantly affected by dietary choline. In conclusion, dietary choline decreased the oxidant damage and regulated the antioxidant system in immune organs of juvenile Jian carp.

Tissue-Specific Fatty Acids Response to Different Diets in Common Carp (Cyprinus carpio L.)

Fish depend on dietary fatty acids (FA) to support their physiological condition and health. Exploring the FA distribution in common carp (Cyprinus carpio), one of the world's most consumed freshwater fish, is important to understand how and where FA of different sources are allocated. We investigated diet effects on the composition of polar and neutral lipid fatty acids (PLFA and NLFA, respectively) in eight different tissues (dorsal and ventral muscle, heart, kidney, intestine, eyes, liver and adipose tissue) of common carp. Two-year old carp were exposed to three diet sources (i.e., zooplankton, zooplankton plus supplementary feeds containing vegetable, VO, or fish oil, FO) with different FA composition. The PLFA and NLFA response was clearly tissue-specific after 210 days of feeding on different diets. PLFA were generally rich in omega-3 polyunsaturated FA and only marginally influenced by dietary FA, whereas the NLFA composition strongly reflected dietary FA profiles. However, the NLFA composition in carp tissues varied considerably at low NLFA mass ratios, suggesting that carp is able to regulate the NLFA composition and thus FA quality in its tissues when NLFA contents are low. Finally, this study shows that FO were 3X more retained than VO as NLFA particularly in muscle tissues, indicating that higher nutritional quality feeds are selectively allocated into tissues and thus available for human consumption.

Impact of acute arsenic and cadmium exposure on the expression of two haeme oxygenase genes and other antioxidant markers in common carp (Cyprinus carpio)

The aim was to study the effects of cadmium (Cd) and arsenic (As) on haeme oxygenases (HOs) and other oxidative stress biomarkers, and their roles in macromolecule damage in liver and kidney of common carp (Cyprinus carpio L.). HOs play a critical role in the defence system against oxidative damage, producing biliverdin and carbon monoxide with important free radical scavenging properties. However, increased HO activity in haeme degradation may also lead to a pro-oxidant effect through the liberation of Fe-modifying Cd and As toxicity. The response of an organism to exposure to toxic metals is in many cases brought about by changes at the level of gene expression. In this study, the genes ho-1 and ho-2 of the common carp were identified, and the changes in gene expressions were analysed from the aspect of Cd and As accumulation. Both ho-1 and ho-2 are transcriptionally induced by Cd and As, but their inductions differ in time course, dose response and tissue specificity. The expression of ho1 was mostly affected by As, primarily in the liver (45-fold), whereas it was enhanced with higher efficacy by Cd in the kidney (25-fold). The cellular redox status and the damage of lipid molecules were monitored via the ratio of reduced to oxidized glutathione, the levels of H2 O2 and lipid peroxidation, and the activities of superoxide dismutase (SOD) and catalase (CAT).