Species Differences In Sensitivity Research Articles

The association between chemical-induced porphyria and hepatic cancer.

The haem biosynthetic pathway is of fundamental importance for cellular metabolism both for the erythroid and nonerythroid tissues. There are several genetic variants of the pathway in the human population that cause dysfunction of one or other of the enzymes resulting in porphyrias of varying severity. Serious chronic hepatic and systemic diseases may result. Some of these can be precipitated by exposure to drugs including hormones, barbiturates and antibiotics, as well as alcohol and particular chlorinated aromatic chemicals. In experimental animals some of the steps of this pathway can also be severely disrupted by a variety of environmental chemicals, potential drugs and pesticides, especially in the liver, leading to the accumulation of uroporphyrins derived from the intermediate uroporphyrinogens or protoporphyrin IX, the immediate precursor of haem. With some of these chemicals this also leads to cholestasis and liver cell injury and eventually hepatic tumours. The review evaluates the available evidence linking hepatic porphyria with carcinogenesis in naturally occurring human genetic conditions and in chemically-induced porphyrias in laboratory animals. The existing data showing gender, strain, and species differences in sensitivity to the chemical-induced porphyrias, liver injury and liver tumours are discussed and the role that transgenically altered mouse models have played in defining the varying mechanisms. Finally, the review proposes a novel, unifying hypothesis linking the hepatotoxicity induced by the accumulation of various porphyrins, with the increased risk of developing hepatic cancer as a long term consequence.

Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dose of DPHP per kg body weight.

Embryo-fetal development studies with the dietary supplement vinpocetine in the rat and rabbit.

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child-bearing potential. Vinpocetine is a semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6-20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose-dependent increases in postimplantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose-dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in postimplantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine.

Species-specific developmental toxicity in rats and rabbits: Generation of a reference compound list for development of alternative testing approaches

For regulatory information requirements, developmental toxicity testing is often conducted in two mammalian species. In order to provide a set of reference compounds that could be used to explore alternative approaches to supersede testing in a second species, a retrospective data analysis was conducted. The aim was to identify compounds for which species sensitivity differences between rats and rabbits are not caused by maternal toxicity or toxicokinetic differences. A total of 330 compounds were analysed and classified according to their species-specific differences. A lack of concordance between rat and rabbit was observed in 24% of the compounds, of which 10% were found to be selective developmental toxicants in one of the species. In contrast to previously published analyses the presented comparison is based entirely on publically data allowing validating and comparing alternative approaches for developmental toxicity testing. Furthermore, this list could be useful to identify mechanisms leading to species differences.

Development of the seed germination and seedling growth test method for determining the difference in species sensitivity of 5 vascular plant species simultaneously

Development of the seed germination and seedling growth test method for determining the difference in species sensitivity of 5 vascular plant species simultaneously

Soil ecological criteria for nickel as a function of soil properties.

Scientific information for the chemistry and ecotoxicology of metals in soils has been obtained in the research conducted in recent years. However, the latest "science" obtained from this research has not yet been translated into "regulations" in China. In the present study, the predicted no effect concentrations (PNECs) for Ni which denoted as soil ecological criteria for Ni were derived based on the effects of soil properties on bioavailability/ecotoxicity of Ni, incorporating the differences in species sensitivity as well as in laboratory and field conditions. First, collected all ecotoxicity data of Ni from bioassays in Chinese soils and filtered with given criteria to obtain reliable data. Second, corrected the compiled data with either aging factor or leaching and aging factors simultaneously to eliminate the discrepancy caused by difference between laboratory and realistic field conditions. Prior to being put into a species sensitivity distribution (SSD) method to fit SSD curves, the corrected Ni ecotoxicity data were normalized with Ni ecotoxicity predictive models to modify the variation in Ni ecotoxicity caused by different soil properties. Then, the hazardous concentration for x% of the species (HCx) was figured out from the Ni SSD curve and the ecological criterion of Ni (PNEC) was set equal to HCx. Finally, predictive models for HCx were developed by quantifying the relationship between the Ni HCx and soil properties. Soil pH was the major factor controlling the values of HCx for Ni, with HC5 varying from 6.5mg/kg in an acidic soil (pH 5.0) to 218.8mg/kg in an alkaline soil (pH 8.5). The predictive models with parameters of soil pH and organic carbon (%) could calculate HCx with determination coefficients (R2) of 0.90-0.95. When soil cation exchange capacity was taken into account the third parameter, the predictive models could predict HCx more accurate with R2 values of 0.94-0.99.

Identifying best-indicator species for abrupt transitions in multispecies communities

Whereas research primarily focuses on understanding under what conditions sudden transitions in the dynamics and functioning of ecological systems may occur, the scale and complexity of ecosystems limit our capacity to achieve this. Indicators of resilience may help circumvent such limitation by signalling the proximity of ecological systems close to an abrupt transition. However, their successful application strongly depends on the ecosystem under question. Therefore, if we aim to use resilience indicators for ecological management in practice, we need to understand where and how they can be reliably monitored. Here, we test the performance of resilience indicators across species in simple modules of competition to help recognize best-indicator species in a community. We show that differences in species sensitivity to disturbances in a community is affected by the dominant eigenvector of the linearized system at equilibrium, We then use simulated time series to compare trends in variance and autocorrelation across species and at community level. We found high heterogeneity in the strength of the indicators across species, while community-based indicators scored better on average than indicators at species level. Looking at species features, we found that collapsing and invading species showed strongest trends, but we observed no relationship between the number of species interaction links and indicators. Lastly, we explored whether it is possible to identify best-indicator species based on their contribution to community variability using eigenvector decomposition methods Our results suggest that successfully identifying a best-indicator species for critical transitions in multispecies communities is not an easy task.

Reconciling seasonal hydraulic risk and plant water use through probabilistic soil-plant dynamics.

Current models used for predicting vegetation responses to climate change are often guided by the dichotomous needs to resolve either (i) internal plant water status as a proxy for physiological vulnerability or (ii) external water and carbon fluxes and atmospheric feedbacks. Yet, accurate representation of fluxes does not always equate to accurate predictions of vulnerability. We resolve this discrepancy using a hydrodynamic framework that simultaneously tracks plant water status and water uptake. We couple a minimalist plant hydraulics model with a soil moisture model and, for the first time, translate rainfall variability at multiple timescales - with explicit descriptions at daily, seasonal, and interannual timescales - into a physiologically meaningful metric for the risk of hydraulic failure. The model, parameterized with measured traits from chaparral species native to Southern California, shows that apparently similar transpiration patterns throughout the dry season can emerge from disparate plant water potential trajectories, and vice versa. The parsimonious set of parameters that captures the role of many traits across the soil-plant-atmosphere continuum is then used to establish differences in species sensitivities to shifts in seasonal rainfall statistics, showing that co-occurring species may diverge in their risk of hydraulic failure despite minimal changes to their seasonal water use. The results suggest potential shifts in species composition in this region due to species-specific changes in hydraulic risk. Our process-based approach offers a quantitative framework for understanding species sensitivity across multiple timescales of rainfall variability and provides a promising avenue toward incorporating interactions of temporal variability and physiological mechanisms into drought response models.

A critical review of polycyclic aromatic hydrocarbon phototoxicity models.

Polycyclic aromatic hydrocarbons (PAHs) are known to exhibit photo-induced toxicity. Hundreds to thousands of PAH parent and substituted compounds are found in the environment, and developing a predictive model applicable to a wide variety of PAHs and organisms is a necessary precursor to environmental risk assessments. There has been evolutionary progress in phototoxicity modeling since 1977. In the present study, a comprehensive review of the models developed to predict phototoxicity of PAHs is presented. The contributions of each of the models to the state of the art are discussed. The models are compared in terms of their scope of applicability to different organisms, PAHs, endpoints (median lethal time and median lethal concentration), and light conditions. The current state of the science that accounts for the key elements of phototoxicity modeling, including the differences in species sensitivity, the partitioning of PAHs into the target lipid of the organisms, and light absorption by the chemicals, as well as light exposure time and conditions, is discussed. In addition, the remaining issues that need to be addressed are explored: the effect of time-varying exposures to light and PAH concentrations, and the lack of a mechanistic understanding that can explain the failure of the Bunsen-Roscoe law of reciprocity. Environ Toxicol Chem 2017;36:1138-1148. © 2016 SETAC.

Species Difference in Sensitivity of Human and Mouse P2X7 Receptors to Inhibitory Effects of Divalent Metal Cations.

P2X7 receptor (P2X7R), a purinergic receptor, is involved in pathophysiological events such as inflammation and cell death, and thus is an attractive target for therapeutic approaches. It is reported that divalent metal cations (DMCs) inhibit P2X7R activation and that there are species differences in their inhibitory effects. To extrapolate the findings in experimental animals to humans, these species differences have to be clarified, but species differences in the sensitivity of P2X7R to DMCs between man and mouse have not been demonstrated. Here we performed direct comparison of the inhibitory effects of DMCs on human and mouse P2X7R activation. Cell lines constitutively expressing human and mouse P2X7R were used, and their P2X7R activation was evaluated as means of YO-PRO-1 dye uptake. MgCl2, NiCl2, ZnCl2, CuCl2 and CaCl2 dose-dependently decreased agonist-induced YO-PRO-1 uptake via both human and mouse P2X7Rs. Apparent differences in the inhibitory profiles for NiCl2 and CaCl2 between them were found, and the IC50 values of DMCs were in the order of CaCl2>MgCl2>NiCl2≈ZnCl2>CuCl2 for both human and mouse P2X7Rs. In this study, we demonstrate that human P2X7R exhibits different sensitivity to nickel and calcium compared with the case of the mouse one, while there is no species difference in the sensitivity of their P2X7Rs to magnesium, zinc and copper, suggesting that the effects of magnesium, zinc and copper on P2X7R-associated pathophysiological events in humans might be predicted from those in mice.

Effects of triclosan on aquatic invertebrates in tropics and the influence of pH on its toxicity on microalgae

The antimicrobial triclosan (TCS) has been detected in household wastewaters (untreated and treated) and receiving environments across the globe. The toxic effects of TCS on temperate standard aquatic test organisms have been widely reported with microalgae being the most sensitive. However, environmental differences between tropical and temperate regions may have selected different trait compositions between these two regions, which in turn may lead to a difference in species sensitivity. Therefore, additional information is required to better characterize risks to organisms in tropics and ensure biodiversity in these regions is not adversely impacted. This study aims to supplement existing TCS toxicity data with five aquatic invertebrates found in tropics and to compare the sensitivity between aquatic invertebrate species from tropical and temperate regions. In addition, the effect of pH on the toxicity of neutral and ionized forms of TCS to microalgae (Chlorella ellipsoidea) was investigated. The reported 96-h LC50 values for the studied invertebrate species ranged from 72 to 962 μg/L. There was no significant difference between the sensitivity of aquatic invertebrate species from tropical and temperate regions. EC50 values for C. ellipsoidea, with and without pH buffer, were significantly different. The findings of this study can be used to support site-specific water quality criteria and environmental risk assessment for TCS in tropical regions. However, further chronic and semi-field experiments with TCS could potentially enable a refined assessment of direct and indirect effects on tropical aquatic communities and further explore functional endpoints of tropical ecosystems.

Traits to stay, traits to move: a review of functional traits to assess sensitivity and adaptive capacity of temperate and boreal trees to climate change

The integration of functional traits into vulnerability assessments is a promising approach to quantitatively capture differences in species sensitivity and adaptive capacity to climate change, allowing the refinement of tree species distribution models. In response to a clear need to identify traits that are responsive to climate change and applicable in a management context, we review the state of knowledge of the main mechanisms, and their associated traits, that underpin the ability of boreal and temperate tree species to persist and (or) shift their distribution in a changing climate. We aimed to determine whether current knowledge is sufficiently mature and available to be used effectively in vulnerability assessments. Marshalling recent conceptual advances and assessing data availability, our ultimate objective is to guide modellers and practitioners in finding and selecting sets of traits that can be used to capture differences in species’ ability to persist and migrate. While the physiological mechanisms that determine sensitivity to climate change are relatively well understood (e.g., drought-induced cavitation), many associated traits have not been systematically documented for North American trees and differences in methodology preclude their widespread integration into vulnerability assessments (e.g., xylem recovery capacity). In contrast, traits traditionally associated with the ability to migrate and withstand fire are generally well documented, but new key traits are emerging in the context of climate change that have not been as well characterized (e.g., age of optimum seed production). More generally, lack of knowledge surrounding the extent and patterns in intraspecific trait variation, as well as co-variation and interaction among traits, limit our ability to use this approach to assess tree adaptive capacity. We conclude by outlining research needs and potential strategies for the development of trait-based knowledge applicable in large-scale modelling efforts, sketching out important aspects of trait data organization that should be part of a coordinated effort by the forest science community.

Community–environment interactions explain octopus-catshark spatial overlap

AbstractThe octopus Eledone cirrhosa and the catshark Scyliorhinus canicula present the same feeding habits and distributional preferences in the Mediterranean Sea. We explore patterns of spatial overlap between these species to address coexistence and infer possible competition from spatial patterns in the western Mediterranean Sea. A spatially explicit modelling approach revealed that spatial overlap mainly responded to the distribution of shared resources, where coexistence is allowed by different ecological processes. Catshark (k-strategy) was highly abundant and widely distributed. However, the fluctuating population dynamics of octopus (r-strategy) explained the variations in spatial patterns of overlap. Spatial structuring across the study area was observed both in population distributions and in species interactions (coexistence or exclusion). Areas with high resources in terms of specific prey items (Catalan Sea) or alternative supplies, such as niche opportunities and ecosystem functions defined by community diversity (Balearic Islands), favoured species coexistence. Sea surface temperature showed opposite effects on overlap in northern and southern regions of the study area, which were not related to differences in species sensitivity. We suggest a surface trophic link, where different phytoplankton communities at each region might have opposite responses to temperature. This triggers contrasting mechanisms of food transfer to deeper benthic communities that subsequently facilitates species overlap. Characterizing how benthic and pelagic seascape properties shape species interactions across space and time is pivotal to properly address community spatial dynamics and move towards ecosystem-based management for sustainable fisheries and conservation planning.

Evolution of Heat Sensors Drove Shifts in Thermosensation between Xenopus Species Adapted to Different Thermal Niches

Temperature is one of the most critical environmental factors affecting survival, and thus species that inhabit different thermal niches have evolved thermal sensitivities suitable for their respective habitats. During the process of shifting thermal niches, various types of genes expressed in diverse tissues, including those of the peripheral to central nervous systems, are potentially involved in the evolutionary changes in thermosensation. To elucidate the molecular mechanisms behind the evolution of thermosensation, thermal responses were compared between two species of clawed frogs (Xenopus laevis and Xenopus tropicalis) adapted to different thermal environments. X. laevis was much more sensitive to heat stimulation than X. tropicalis at the behavioral and neural levels. The activity and sensitivity of the heat-sensing TRPA1 channel were higher in X. laevis compared with those of X. tropicalis The thermal responses of another heat-sensing channel, TRPV1, also differed between the two Xenopus species. The species differences in Xenopus TRPV1 heat responses were largely determined by three amino acid substitutions located in the first three ankyrin repeat domains, known to be involved in the regulation of rat TRPV1 activity. In addition, Xenopus TRPV1 exhibited drastic species differences in sensitivity to capsaicin, contained in chili peppers, between the two Xenopus species. Another single amino acid substitution within Xenopus TRPV1 is responsible for this species difference, which likely alters the neural and behavioral responses to capsaicin. These combined subtle amino acid substitutions in peripheral thermal sensors potentially serve as a driving force for the evolution of thermal and chemical sensation.

Effects of endosulfan in freshwater pond communities

AbstractPesticide use has led to ubiquitous contamination of natural habitats that can cause direct and indirect effects on nontarget organisms. Laboratory toxicity tests are valuable for evaluating the direct lethal effects of pesticides, but whether species differences in sensitivity identified from such tests are representative of more natural conditions is unknown. Studies of pesticide effects on communities are needed to understand the indirect effects of pesticides, but many such studies are focused on simplified communities and overlook the contribution of higher trophic levels (i.e., lethal predators), which can have interactive effects with pesticides and may play a large role in influencing community dynamics in contaminated habitats. Much of the research investigating pesticides in communities has focused on organophosphates, carbamates, and pyrethroids, whereas organochlorines are understudied, despite the fact that they can be highly toxic and persist in the environment. We investigated the e...

Developmental toxicity of PFOS and PFOA in great cormorant (Phalacrocorax carbo sinensis), herring gull (Larus argentatus) and chicken (Gallus gallus domesticus).

Perfluoroalkyl acids (PFAAs) are found globally in environmental samples and have been studied in various species. In this study, we compare the sensitivity of three avian species to the toxic effects of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Eggs of great cormorant (Phalacrocorax carbo sinensis), herring gull (Larus argentatus) and the domestic White Leghorn chicken (Gallus gallus domesticus) were exposed in ovo by injection into the air sac. Effects on embryo survival were observed following exposure to PFOS and PFOA in chicken and herring gull. Chicken was found to be the most sensitive species with 50% reduced embryo survival at 8.5μg/g egg for PFOS and 2.5μg/g egg for PFOA. Cormorant was shown to be the least sensitive species. The difference in sensitivity between chicken and herring gull was a factor of 2.7 for PFOS and 3.5 for PFOA. Between chicken and great cormorant, the sensitivity difference was 2.6 for PFOS and 8.2 for PFOA. Effects on embryo survival were seen at egg injection doses of PFOS close to levels found in environmental samples from wild birds, indicating that PFOS could be having effects in highly exposed populations of birds. This study also shows that there are differences in species sensitivity to PFOS and PFOA that should be taken into consideration in avian wildlife risk assessment.

Review of the Ecotoxicological Properties of the Methylenedianiline Substances.

Concerning chronic toxicity, D. magna is the most sensitive species tested against MDA aquatic exposures, with a 21days-NOEC of 0.00525mg/L. Exposure of daphnids takes place via the aquatic phase. Other species of the same phylum (Arthropoda) appear to be less sensitive albeit with exposures via soil or sediment, with a 28days-NOEC of 562mg/kg d. w. soil (F. candida) and 41.3mg/kg d. w. sediment (Hyalella azteca), for reproductive and survival endpoints, respectively. Also for acute toxicity, D. magna is more sensitive than the other species, with an 48h-EC50 that spreads over two orders of magnitude, ranging from 0.019 to 2.7mg/L. Fish show a more uniform reaction to MDA, with 96h-LC50 ranging from about 20 to 60mg/L; chronic data for fish are not available. Acute toxicity data for algae and cyanobacteria are in the range of 1-10mg/L; based on growth rate, the 72h-NOECr or ErC10 of MDA to algae is 0.3-9.3mg/L.For sediment organisms, the black worm L. variegatus shows the highest sensitivity against MDA with a NOEC between ≤3.75mg/kg and 30mg/kgd. w., followed by the amphipod H. azteca. The lower sensitivity of L. variegatus in the second study compared to the first study is obviously attributable to the different feeding regimes (semi-continuous feeding against pre-spiked sediment). One argument might be that semi-continuous feeding allows the organisms to avoid the contaminated food. However, a change from semi-continuous feeding to sediment pre-spiked with nettle powder (Urtica sp.) results in an earlier and much stronger increase in ammonia concentration in the system. This became apparent after both studies on the blackworm were finalized. The ammonia 96h-EC50 for the blackworm is 0.69mg/L at pH = 8.2, and the 96h-EC10 at pH = 8.2 is 0.33mg/L (Hickey and Vickers, Arch Environ Contam Toxicol 26:292-298, 1994). As a result, the lower NOEC and LOEC in the second study with L. variegatus are probably attributable to interference by ammonia.MDA binds irreversibly to soil and sediment which may explain the general, but not uniform lower sensitivity of soil and sediment organisms against aquatic organisms. However, species with intense soil or sediment contact (L. variegatus and E. fetida) show in general lower NOEC values than those organisms with less direct contact (3.75 and 11.2mg/kg d. w., respectively). On the one hand it may be hypothesized that this intense contact to soil bound MDA is one reason for the higher sensitivity; on the other hand, metabolic capacity against MDA of the organisms tested is unknown at this point in time and might as well explain differences in species sensitivity. For plants there are only acute data available, and in respect to acute toxicity L. sativa is more sensitive to MDA than E. fetida.Limited aquatic data available so far do not indicate that the toxicity of pMDA is different to MDA. In addition, the limited set of data generated with the marine M. macrocopa (crustacean), N. fustulum (diatom) and V. fisheri (bacteria) do not indicate that sea water organisms are more sensitive to MDA than fresh water organisms.In mammals, MDA is unlikely to interact with the endocrine sexual system; interaction with the adrenergic system cannot be ruled out, and effects of MDA on the thyroid hormone system have been demonstrated. MDA inhibits the thyroid peroxidase which might contribute to the thyroid gland tumors observed in chronic studies with rats and mice. Some anti-androgenic activity in in vitro studies with yeast cell did not prevail in in vivo studies with rats and mice.

Risk Functions of Dolphins and Sea Lions Exposed to Sonar Signals.

Acoustic dose-response functions have been recommended as a means of predicting behavioral impacts on marine mammals from anthropogenic noise exposure. Thirty bottlenose dolphins and fifteen sea lions participated in a controlled exposure study to explore dose-response relationships to the received level of a simulated sonar signal. Both species showed an increase in the probability of response and in the severity of response with increased received levels. Differences in species sensitivity were noted in habituation and the impact of age on responsiveness.

Relationship between herbicide mode of action and difference in species sensitivity of aquatic primary producers

Relationship between herbicide mode of action and difference in species sensitivity of aquatic primary producers

Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models.

Contrast-induced acute kidney injury (CI-AKI) can occur in 3–25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments.