A Randomized Trial of Valganciclovir Prophylaxis Versus Preemptive Therapy in Kidney Transplant Recipients.

SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood.

Background: Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients. Methods: A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification. Results: We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years. Conclusions: We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.

Insufficient response to mRNA SARS-CoV-2 vaccine and high incidence of severe COVID-19 in kidney transplant recipients during pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.

Rejection-associated Phenotype of De Novo Thrombotic Microangiopathy Represents a Risk for Premature Graft Loss.

BACKGROUND: Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood. METHODS: In this multicenter, retrospective, case-control paired study designed to control for donor-associated risks, we assessed the recipients' risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93). Graft follow-up was initiated at the time of TMA diagnosis and at the same time in the corresponding paired kidney graft. RESULTS: The TMA group displayed higher peak panel-reactive antibodies, more frequent retransplantation status, and longer cold ischemia time in univariable analysis. In the multivariable regression model, longer cold ischemia times (odds ratio, 1.18; 95% confidence interval [CI], 1.01-1.39; P = 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06; P = 0.005) were found to be associated with increased risk of de novo TMA. The risk of graft failure was higher in the TMA group at 5 y (hazard ratio [HR], 3.99; 95% CI, 2.04-7.84; P < 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87; P < 0.001). De novo TMA associated with the active antibody-mediated rejection was associated with higher risk of graft failure at 5 y (HR, 3.43; 95% CI, 1.69-6.98; P < 0.001) compared with other TMA. CONCLUSIONS: Longer cold ischemia and allosensitization play a role in de novo TMA development, whereas TMA as a part of active antibody-mediated rejection was associated with the highest risk for premature graft loss.

Chronic simultaneous exposure of common carp (Cyprinus carpio) from embryonic to juvenile stage to drospirenone and gestodene at low ng/L level caused intersex.

Synthetic progestins are emerging contaminants of the aquatic environment with endocrine disrupting potential. The main aim of the present study was to investigate the effects of the synthetic progestins gestodene, and drospirenone on sex differentiation in common carp (Cyprinus carpio) by histological analysis. To gain insights into the mechanisms behind the observations from the in vivo experiment on sex differentiation, we analyzed expression of genes involved in hypothalamus-pituitary-gonad (HPG) and hypothalamus-pituitary-thyroid (HPT) axes, histology of hepatopancreas, and in vitro bioassays. Carp were continuously exposed to concentrations of 2 ng/L of single progestins (gestodene or drospirenone) or to their mixture at concentration 2 ng/L of each. The exposure started 24 h after fertilization of eggs and concluded 160 days post-hatching. Our results showed that exposure of common carp to a binary mixture of drospirenone and gestodene caused increased incidence of intersex (32%) when compared to clean water and solvent control groups (both 3%). Intersex most probably was induced by a combination of multiple modes of action of the studied substances, namely anti-gonadotropic activity, interference with androgen receptor, and potentially also with HPT axis or estrogen receptor.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.

Viral load and duration of BK polyomavirus viraemia determine renal graft fibrosis progression: histologic evaluation of late protocol biopsies.

BACKGROUND: Polyomavirus BK (BKV) infection of the renal allograft causes destructive tissue injury with inflammation and subsequent fibrosis. METHODS: Using a prospective cohort of patients after kidney transplantation performed between 2003 and 2012, we investigated the role of BKV viraemia in the development and progression of interstitial fibrosis and tubular atrophy (IFTA). The primary outcome was moderate-to-severe IFTA assessed by protocol biopsy at 36 months. RESULTS: A total of 207 consecutive recipients were enrolled. Of these, 57 (28%) developed BKV viraemia with 10 (5%) cases of polyomavirus-associated nephropathy (PVAN). Transient (<3 months) BKV viraemia occurred in 70% of patients, and persistent (≥3 months) BKV viraemia in 30%. A high viral load (≥10 000 copies/mL) was detected in 18% and a low viral load (<10 000 copies/mL) in 61%, while the viral load could not be determined in 21%. Moderate-to-severe IFTA was significantly increased in high [71%; odds ratio (OR) = 12.1; 95% confidence interval (CI) 1.62-90.0; P = 0.015] or persistent BKV viraemia (67%; OR = 6.33; 95% CI 1.19-33.7; P = 0.031) with corresponding rise in 'interstitial fibrosis + tubular atrophy' scores. Only patients with transient low BKV viraemia showed similar incidence and progression of IFTA to the no-BKV group. Persistent low BKV viraemia was uncommon yet the progression of fibrosis was significant. Only recipients with PVAN experienced inferior graft survival at 5 years. CONCLUSIONS: These data suggest that only transient low BKV viraemia does not negatively affect the progression of allograft fibrosis in contrast to excessive risk of severe fibrosis after high or persistent BKV viraemia.

Effect of polycyclic musk compounds on aquatic organisms: A critical literature review supplemented by own data.

Synthetic musk compounds are extensively used in personal care and cosmetic products around the world. Because they are not completely removed in sewage treatment plants, they eventually end up in aquatic environments. The aim of this review was to summarize published information on effects of polycyclic musks on aquatic organisms and to discuss whether the experimental design of toxicological studies involving these substances could influence the results obtained. With the exception of one study run in a flow-through system, all published toxicological studies on synthetic polycyclic musks have been conducted in semi-static or even static systems. Based upon data in the literature and our own results, we conclude that in toxicological tests with semi-static set-ups, concentrations of polycyclic musks decrease with time between bath exchanges, and, as a result, tested organisms are not being exposed to stable concentrations but rather to concentration pulses. The duration and character of these pulses are influenced mainly by aeration of experimental baths, as polycyclic musks have a tendency to volatilize from water baths. Under semi-static conditions, tested organisms may be subjected to lower concentration of the tested substance for relatively long periods. Those levels may even fall below the limits of quantification. During these periods, some level of detoxification and/or elimination (depuration) of the toxicant may reduce toxic effect of the previous exposures. Consequently, toxicity of polycyclic musk substances for aquatic organisms obtained under these conditions may be underestimated. Based upon existing data in the literature, therefore, it is very difficult to correctly estimate risk of polycyclic musks to aquatic organisms.

[Cytomegalovirus and polyomavirus infection after renal transplantation]. / Cytomegalovirová a polyomavirová infekce po transplantaci ledviny.

Viral infections are among the most common infectious complications affecting transplant recipients. Due to immunosuppressive therapy predominantly affecting cellular immunity and thus successfully reducing the incidence of acute rejection, there is a higher incidence of viral infections. Herpesviruses and polyomaviruses are ubiquitous pathogens which have the ability to persist in a state of latent infection. In addition to post-transplant reactivation, donor-induced primoinfection can also occur, leading to increased morbidity and contributing to decreased survival of patients. Moreover, there are long-term indirect effects, resulting in an impaired function of the transplanted organs and their premature loss. This article provides a brief overview of infections which have the greatest impact on transplant recipients, i.e. cytomegalovirus and BK polyomavirus, their diagnosis, prevention and treatment.Key words: BK virus - cytomegalovirus - ganciclovir - immunosuppressive therapy - JC virus - kidney transplantation - polyomavirus - polyomavirus-associated nephropathy - preemptive therapy - prophylaxis - valaciclovir.

Effects of prometryne on early life stages of common carp (Cyprinus carpio L.).

Toxicity of prometryne to early life stages of common carp was assessed. On the basis of accumulated mortality in the experimental groups lowest observed-effect concentration (LOEC) was estimated as 1100 µg/l; and no observed-effect concentration (NOEC) was 850 µg/l. Fulton's condition factor was significantly lower than in controls in fish exposed to 4000 µg/l after 7, 14, and 21 days. By day 14, fish exposed to 4000 µg/l prometryne showed significantly lower mass and total length compared to controls. Fish exposed the 1200 and 4000 µg/l showed delay in development, severe hyperaemia in gill, liver, and caudal and cranial kidney. Subchronic prometryne exposure of early-life stages of common carp at concentrations of 1200 and 4000 µg/l affected their survival, growth rate, early ontogeny, and histology.

Effects of acute exposure to deltamethrin and recovery time on common carp (Cyprinus carpio L.).

OBJECTIVES: The aim of this study is to evaluate effects of the insecticide Decis Mega (DM; active substance deltamethrin 50 g.L(-1)) on common carp on the basis of haematological profile, oxidative stress, antioxidant enzymes and histopathology. DESIGN: Fish were exposed two concentrations of DM 6.56 µg.L(-1) (1DM) and 65.6 µg.L(-1) (2DM) for 96 h. Then the remaining fish were transferred into DM-free water for depuration for another period of 96 h. RESULTS: Exposure to 1DM and 2DM proved effect on enzymatic activity of superoxide dismutase, catalase, glutathione reductase and on oxidative damage of cells in gills, liver and kidney (p<0.05, p<0.01). Exposure to 1DM showed differences (p<0.05, p<0.01) in hematocrit and hemoglobin in blood. Histopathological changes were observed after acute exposure to DM as well as to DM-free water in gills, liver and kidney. CONCLUSION: This study concludes that deltamethrin has influence on the haematological parameters, activity of antioxidant enzymes and caused oxidative damage, and histopathological changes in the fish. However, antioxidant balance in the body was restored after placing the fish in clean water for 4 days, however, this time was not sufficient complete regeneration.

Effects of cyhalothrin-based pesticide on early life stages of common carp (Cyprinus carpio L.).

The effects of Nexide (a.i. gamma-cyhalothrin 60 g L(-1)) on cumulative mortality, growth indices, and ontogenetic development of embryos and larvae of common carp (Cyprinus carpio L.) were studied. Levels of oxidative stress parameters glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), glutathione-S-transferase (GST), and lipid peroxidation were determined. Eggs of newly fertilised common carp were exposed to Nexide at concentrations 5, 25, 50, 100, and 250 µ g L(-1) (0.3, 1.5, 3, 6, and 15 µ g L(-1) gamma-cyhalothrin). All organisms exposed to concentrations higher than 50 µ g L(-1) died soon after hatching; at 25 µ g L(-1), 95% mortality was recorded. Larvae exposed to 5 µ g L(-1) showed significantly lower growth and retarded ontogenetic development compared to control. Histological examination of the livers of larvae from the exposed group revealed dystrophic changes. The value of detoxification enzyme GST of organisms from the exposed group was significantly higher compared to the control and the value of defensive enzyme GPx was significantly lower compared to the control. The results of our investigation confirmed that contamination of aquatic environment by pesticides containing cyhalothrin may impair growth and development of early life stages of carp and cause disbalance of defensive enzymes.

Effect of terbuthylazine-2-hydroxy at environmental concentrations on early life stages of common carp (Cyprinus carpio L.).

The aim of the study was to investigate effects of the triazine's herbicide terbuthylazine-2-hydroxy on early life stage of common carp (Cyprinus carpio L.) through antioxidant indices, mortality, growth, development, and histopathology. Based on accumulated mortality in the experimental groups, lethal concentrations of terbuthylazine-2-hydroxy were estimated at 35-day LC50 = 10.9 mg/L terbuthylazine-2-hydroxy. By day 15, fish were exposed to 3.5 mg/L and by day 26, fish were exposed to 0.0029 mg/L; real environmental concentration in Czech rivers, 0.07 mg/L, 1.4 mg/L, and 3.5 mg/L terbuthylazine-2-hydroxy, showed significantly lower mass and total length compared with controls. Based on inhibition of growth in the experimental groups, lowest observed effect concentration (LOEC) = 0.002 mg/L terbuthylazine-2-hydroxy and no observed effect concentration (NOEC) = 0.0001 mg/L terbuthylazine-2-hydroxy. No significant negative effects on hatching or embryo viability were demonstrated at the concentrations tested, but significant differences in early ontogeny among groups were noted. Fish from the two highest tested concentrations showed a dose-related delay in development compared with the controls. Total superoxide dismutase (SOD) activity was significant lower in all groups testedly for terbuthylazine-2-hydroxy compared with the control group. At concentrations of 1.4 and 3.5 mg/L damage to caudal kidney tubules when compared to control fish was found.

Effect of zeta-cypermethrin on common carp (Cyprinus carpio L.).

OBJECTIVES: The aim of this study was to assess the effect of pesticide Fury 10 EW, containing zeta-cypermethrin 100 g.l-1, on common carp (Cyprinus carpio L.). DESIGN: The toxicity tests were performed on common carp according to OECD 203 methodologies. The common carp were exposed to Fury 10 EW at concentrations, 5, 7, 10, 50 and 100 µg.l-1 for 96 h and compared to common carp in a non-treated control group. Acute toxicity tests were detected value 96hLC50=13.8 µg.l-1. On the basis of the results was assessed the effect on the hematological profile, oxidative stress parameters, and antioxidants biomarkers in tissues, in another acute test. RESULTS: The observed 96hLC50 value of Fury 10 EW was 13.8 µg.l-1. A significantly lower large lymphocyte and monocyte count, and a significantly greater number of segmented eosinophil granulocyte and higher hematocrit was found in the pesticide-exposed common carp compared to controls. Oxidative damage was not detected in the experimental common carp, however there were significant differences from control in superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in tissue after acute exposure to 13.8 µg.l-1 Fury 10 EW. CONCLUSIONS: Zeta-cypermethrin as Fury 10 EW was classified as a substance highly toxic to fish. The hematological profile well oxidative stress parameters and antioxidant defensive systems provide important information about the internal environment of organisms. There is a lack of experimental results about the effects of zeta-cypermethrin on fish in the literature.

Toxic effects, bioconcentration and depuration of verapamil in the early life stages of common carp (Cyprinus carpio L.).

Verapamil is a pharmaceutical that belongs to a group of calcium channel blockers and is mainly used as a treatment of angina pectoris and arterial hypertension. Verapamil has been detected in aquatic environments in concentrations ranging from ng L(-1) to µg L(-1). In the present study, a series of acute toxicity tests of verapamil on various developmental stages of common carp (Cyprinus carpio) were conducted. As a result, 96hLC50 values of verapamil were estimated at 16.4±9.2, 7.3±1.5 and 4.8±0.2 mg L(-1) for embryos (E5-E9) and common carp larvae L2 and L5, respectively. Lethal concentrations of verapamil decreased with an increase in the age of the fish. Acute exposure to verapamil significantly reduced the heart rate in the embryos and larvae. In an embryo-larval toxicity test (sub-chronic exposure), the bioconcentration, depuration, and toxic effects of verapamil were assessed in common carp. The fish were exposed to verapamil in a concentration of 0.463 (environmentally relevant), 4.63, 46.3 and 463 µg L(-1). Verapamil had no effect on the accumulated mortality, hatching, condition factor, growth or ontogeny of the fish in any of the tested concentrations. In carp exposed to 463 and 46.3 µg L(-1) of verapamil, significantly higher occurrences of malformations and edemas were observed compared to the control. The bioconcentration factor of verapamil in whole fish homogenates ranged between 6.6 and 16.6 and was therefore below the critical value for hazard substances (BCF>500). The half-life and the 95% depuration time for the tested compound were estimated to be 10.2±1.6 days and 44.2±8.6 days, respectively. No effects of verapamil on the studied endpoints were observed at environmentally relevant concentrations.

Multiple biomarkers responses in juvenile rainbow trout, Oncorhynchus mykiss, after acute exposure to a fungicide propiconazole.

In this study, the toxic effects of propiconazole (PCZ), a triazole fungicide present in aquatic environment, were studied in juvenile rainbow trout, Oncorhynchus mykiss, by acute toxicity test with the concentration of 5.04 mg/L (96 h LC50). Morphological indices, hematological parameters, liver xenobiotic-metabolizing response, and tissue antioxidant status were evaluated. Compared with the control group, fish exposed to PCZ showed significantly higher Leuko, PCV, MCHC, and hepatic EROD, and significantly lower MCV. CF and HSI were not significantly different among groups. SOD, CAT, GPx, and GR activities increased significantly in liver of experimental groups, but decreased significantly in gill. In general, antioxidant enzyme activity in intestine was less evident than in liver. Oxidative stress indices (levels of LPO and CP) were significantly higher in gill. Additionally, through chemometrics of all parameters measured in this study, two groups with 67.29% of total accumulated variance were distinguished. In short, the physiological and biochemical responses in different tissues of fish indicated that PCZ-induced the stressful environmental conditions. But according to PCZ residual status in the natural environment, more long-term experiments at lower concentrations will be necessary in the future. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

Effect of chronic exposure to simazine on oxidative stress and antioxidant response in common carp (Cyprinus carpio L.).

We investigated the chronic effect of simazine, an s-triazine herbicide commonly present in aquatic environments, on the antioxidant system and oxidative stress indices in common carp (Cyprinus carpio L.). Fish were exposed to sub-lethal concentrations of 0.06 µg l(-1) (environmental concentration in Czech rivers), 2 mg l(-1), and 4 mg l(-1) for 14, 28 and 60 days. Indices of oxidative stress [reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS)], and antioxidant parameters [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH)] in fish brain, gill, muscle, liver, and intestine were measured. Chronic exposure to simazine showed the impact of the increased production of ROS leading to oxidative damage to lipids, proteins, and inhibition of antioxidant capacity. Activity of the antioxidant enzymes SOD, CAT, GPx and GSH in groups with high concentrations (2 mg l(-1), 4 mg l(-1)) increased at 14 and 28 days, but decreased after 60 days exposure (p<0.01) as compared with the control group. Changes in enzyme activity were mainly in the liver, but also in gills and brain. Prolonged exposure to simazine resulted in excess ROS formation finally resulting in oxidative damage to cell lipids and proteins and also inhibited antioxidant capacities in common carp tissue.

Effects of low-concentrations of simazine on early life stages of common carp (Cyprinus carpio L.).

OBJECTIVES: The aim of this study is to assess the toxicity of simazine in different developmental stages of common carp (Cyprinus carpio) on the basis of mortality, early ontogeny, occurrence of morphological anomalies, growth rate, and Fulton's condition factor during and at the conclusion of the test. DESIGN: The toxicity tests were performed on carp according to OECD 210 methodologies. The developmental stages of carp were exposed to simazine at four concentrations, 0.06, (reported concentration in Czech rivers), 60, 600, and 3000 µg/l for 36 days and compared to carp in a non-treated control group. RESULTS: Simazine in concentration 0.06 µg/l had no effect on early life stages of carp. Simazine in concentration 600 and 3000 µg/l caused decrease of mass and total length of carp. Fish exposed to three highest levels of simazine showed alteration of tubular system of caudal kidney. On the basis of histopatological changes the values of LOEC = 60 µg/l, NOEC = 0.06 µg/l for simazine were estimated. CONCLUSIONS: Chronic simazine exposure of early-life stages of common carp affected their growth rate, and histology. Some of the changes were observed only at higher exposures (600, 3000 µg/l), but change founded in caudal kidney was affected in fish exposed to the second lowest concentration tested (i.e., 60 µg/l), which is about 10 µg/l higher than reported in Colorado rivers in recent years. Concentrations of simazine in World rivers have been reported to generally vary in the range 0.0003-49.20 µg/l.

Effect of chronic exposure to prometryne on oxidative stress and antioxidant response in early life stages of common carp (Cyprinus carpio L.).

OBJECTIVES: The aim of the study was to investigate effects of the triazine herbicide prometryne on early life stages of common carp Cyprinus carpio as indicated by oxidative stress and antioxidant indices. DESIGN: Toxicity tests were performed according to OECD 210 methodologies. Common carp larvae and embryos exposed for 35 days to prometryne at three concentrations, 0.51 (reported concentration in Czech rivers), 80 (1% 96 h LC50), and 1200 (15% 96 h LC50) µg/l, were compared to carp in a non-treated control group. Activity of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR), as well as levels of thiobarbituric acid reactive substances (TBARS) were assessed. RESULTS: Chronic exposure of early life stages of carp to prometryne showed no effect on growth and mortality rates. Levels of oxidative damage in fish test groups showed no significant differences from the controls. Glutathione reductase activity at exposure 0.51 µg/l was significantly increase (p<0.01) compared with controls and other exposures. CONCLUSION: The chronic exposure to prometryne showed no influence on oxidative stress. Differences from control fish was observed in GR activity in exposure prometryne 0.51 µg/l.