Examination of organs and tissues of adult sheep grazed in an area with possible intoxication with rocket fue, Kazakhstan

The authors have conducted experiments to study the pathoanatomical and histological pattern of organs and tissues of adult sheep affected by unsymmetric dimethylhydrazine (UDMH). This highly toxic fuel was spilled on the territory of the Karsakpay and Ulytau districts of Karaganda region, Kazakhstan, because of the fall of the rocket 'Proton­M' after an unsuccessful launch from the Baikonur cosmodrome in 2007. In the experiment, the study group was consisted of 7 adult sheep that grazed in the area of possible intoxication with rocket fuel UDMH. The main objects of the study were histological preparations obtained from fixed structures. As the structures have a flat contrast and are poorly detected in the ordinary light microscope, the specially processed preparations were used. After preparing, the authors studied organs and tissues using a microscope, which allowed to reveal in detail the level of damage caused by intoxication and to establish the negative effect of UDMH on the internal organs. The group of sheep showed a high index of macroscopic signs of interstitial pneumonia (85.7 ± 14.3%), and histologically quite high index was granulomatous inflammation of liver (71.4 ± 18.4%). Kidneys also showed a high level of abnormalities.

Potential toxicity evaluation and comparison within multiple mice organs after repeat injections of linear versus macrocyclic gadolinium-based contrast agents: A comprehensive and time course study.

As nephrogenic systemic fibrosis (NSF) and increased signal intensities in deep cerebellar nuclei (DCN) were successively discovered in renal insufficiency patients and healthy persons after gadolinium-based contrast agents (GBCAs) exposure, an awareness of potential toxicity with GBCAs exposure has been heightening. Herein, we performed a multi-organ/tissue toxicity assessment after different GBCAs administration with a large number of samples, and long-term, time-course schedule investigation. ICR mice were randomized to five exposure groups (n = 42/group) and received intravenous injection of GBCAs (2.5 mmol Gd/kg) or saline four time a week for 5 consecutive weeks. Gadolinium concentration detection, sensory tests, histological and hematological analyses were performed at corresponding timepoints (4th or 6th or 10th week). Our results showed that (i) gadodiamide could cause reversible vacuolar changes in the renal tubular epithelial cells, which appeared at 6th week and recovered at 10th week, and severe skin lesion in mice tail with consecutive injection for 10 weeks, that (ii) linear GBCAs (gadodiamide and gadopentetate dimeglumine) markedly elevated heat hyperalgesia and white blood cells of mice at 6th week and most of these changes could recovery at 10th week, and that (iii) linear GBCAs exhibited more gadolinium retention in multi-organ/tissue versus macrocyclic GBCAs and in most case, linear GBCAs showed faster accumulation and regression speed in examined tissues than macrocyclic GBCAs excepting gadodiamide in skin which showed slowest regression speed. Collectively, macrocyclic GBCAs presents more stable, lower propensity to release Gd and safer profiles versus linear GBCAs.

The effect of Artichoke (Cynara scolymus L.) on the expression of calcium-binding proteins in the eggshell gland of laying hens.

The purpose of the present work is to investigate the effect of dietary-supplemented artichoke (Cynara scolymus L.) on the mRNA expression of calbindin 1 (Calb1), osteopontin (Spp1), albumin (Alb) and CALB1 protein in the eggshell gland (ESG) of laying hens. A total of 80 ISA Brown hens (each at 40 weeks of age) were randomly divided into two groups: a control and a treated group. All poultry received 130 g/day of compound feed for laying hens but the treated hens' diet was also supplemented with 3g/kg of dried and milled artichoke (Cynara scolymus L.). The increase of the Ca content in blood of the treated hens was established. Significantly decrease of Spp1 mRNA transcripts was found in the eggshell gland of the treated hens, while the mRNA level of Alb was increased. The relative expression of Calb1 mRNA tended to increase in the treated group. The expression of calbindin protein in the cytoplasm of glandular cells of the shell gland was defined by immunohistochemical method. Very strong signals of calbindin were observed in the treated group. The supplementation of the laying hens' diet with dried artichoke (C. scolymus L.) led to a significant increase of Ca content in blood that was reflected in the changes of expression of the eggshell gland genes involved in the mineralization of eggshell.

Pesticides and transgenerational inheritance of pathologies: Designing, analysing and reporting rodent studies.

Single-centre studies examining the transgenerational inheritance of pathologies in rodents exposed to pesticides have not always taken important design and analysis issues into account. This paper examines these methodological and statistical issues in detail. Its particular focus is on the estimation of 'litter effects': the tendency for rodents within a litter to be more alike than rodents in different litters. Appropriate statistical models were fitted to published data from a series of widely reported studies carried out at Washington State University. These studies were amalgamated into a single dataset in order to estimate these litter effects and associated treatment effects. Litter effects varied by outcome and were often substantial. Consequently, the effective sample size was often substantially less than the number of observations with implications for the power of the studies. Moreover, the reported precision of the estimates of treatment effects was too low. These problems are exacerbated by unexplained missing data across generations. Researchers in the life sciences could be more cognisant of the guidelines established in medicine for reporting randomised controlled trials, particularly cluster randomised trials. More attention should be paid to the design and analysis of multi-generational rodent studies; their imperfections have important implications for assessments of the evidence relating to the risks of pesticides for public health.

Active Notch signaling is required for arm regeneration in a brittle star.

Cell signaling pathways play key roles in coordinating cellular events in development. The Notch signaling pathway is highly conserved across all multicellular animals and is known to coordinate a multitude of diverse cellular events, including proliferation, differentiation, fate specification, and cell death. Specific functions of the pathway are, however, highly context-dependent and are not well characterized in post-traumatic regeneration. Here, we use a small-molecule inhibitor of the pathway (DAPT) to demonstrate that Notch signaling is required for proper arm regeneration in the brittle star Ophioderma brevispina, a highly regenerative member of the phylum Echinodermata. We also employ a transcriptome-wide gene expression analysis (RNA-seq) to characterize the downstream genes controlled by the Notch pathway in the brittle star regeneration. We demonstrate that arm regeneration involves an extensive cross-talk between the Notch pathway and other cell signaling pathways. In the regrowing arm, Notch regulates the composition of the extracellular matrix, cell migration, proliferation, and apoptosis, as well as components of the innate immune response. We also show for the first time that Notch signaling regulates the activity of several transposable elements. Our data also suggests that one of the possible mechanisms through which Notch sustains its activity in the regenerating tissues is via suppression of Neuralized1.

Effect of lithium chloride on d-galactose induced organs injury: Possible antioxidative role.

The aging process is concerned with oxidative stress and causing malfunction of various organs such as the liver, kidney and heart. Lithium (Li) salts have shown anti-manic, anti-suicidal, and antioxidant properties. The current study is aimed to evaluate the possible inhibitory effects of various doses (10, 20 & 40mg/ml/kg) of Lithium chloride (LiCl) on D-galactose (D-gal)-produced aging model and explore the underlying mechanism. In the study 40 male rats were randomly alienated into 8 groups i.e. saline, LiCl (10, 20 & 40mg/ml/kg), D-gal and D-gal+LiCl (10, 20 & 40 mg/ml/kg). D-gal was given at a dosage of 300mg/ml/kg$ and animals received their respective treatment for 6 weeks [intraperitoneally (I.P), once daily]. After 2 weeks animals were decapitated and organs (liver, kidney, and heart) were removed for antioxidant assays. Blood was also collected for biochemical parameters. LiCl substantially decreased oxidative strain marker and increased enzymatic antioxidants in the liver, kidney, and heart of D-gal treated rats. LiCl also decreased serum alanine aminotransferase (ALT), aspartate transaminase (AST), creatine, urea, CK-MB, triglyceride, cholesterol, low-density lipoprotein (LDL) and increased high-density lipoprotein (HDL) in D-gal treated animals. High dose (80mg/ml/kg) of LiCl observed as the most effective dose against D-gal induced alterations. These finding LiCl inhibits D-gal induced liver, kidney and heart damages via its antioxidant potential.

Ticks home in on body heat: A new understanding of Haller's organ and repellent action.

Ticks are second only to mosquitoes as vectors of disease to humans and animals. Tick host detection is mainly ascribed to Haller's organ, a complex sensory structure on the tick foreleg that detects odors, carbon dioxide and heat, but these host detection mechanisms are not well understood. There is anecdotal evidence that ticks and other ectoparasites are attracted to heat, but it has never been demonstrated that they use radiant heat to detect hosts at a distance. In fact, previous attempts to do this have concluded that radiant heat was not used by ticks. Here we use a novel thermotaxis assay to investigate the detection range, temperature dependence and repellent sensitivity of heat perception in ticks and to identify the sensory organ responsible for this sense. We show that Amblyomma americanum and Dermacentor variabilis ticks can locate a human from several meters away by radiant heat sensed by the part of Haller's organ known as the capsule, a covered spherical pit organ. An aperture in the capsule cover confers directionality and highly reflective interior surfaces of the capsule concentrate radiation on the sensilla to sharpen directionality and increase sensitivity. Commercial insect repellents provide an effective means of personal protection against potentially infectious tick bites by hindering host-seeking behavior. Low concentrations of the insect repellents DEET, picaridin, 2-undecanone, citronellal and nootkatone eliminate thermotaxis without affecting olfaction-stimulated host-seeking behavior. Our results demonstrate that the tick Haller's organ capsule is a radiant heat sensor used in host-finding and that repellents disrupt this sense at concentrations that do not disrupt olfaction. We anticipate that this discovery will significantly aid insect repellent research and provide novel targets for the development of innovative integrated pest management programs and personal protection strategies for ectoparasites and vector-borne disease.

Fluorescent nanoparticles in the popular pizza: properties, biodistribution and cytotoxicity.

Food-borne nanoparticles that are generated during the thermal processing of various consumed foods are of great concern due to their unique properties. In this study, the presence of fluorescent nanoparticles (FNPs) in pizza, their biodistribution and cytotoxicity were investigated. The spherical FNPs have a diameter of about 3.33 nm. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analysis revealed that they contained 68.21% C, 27.44% O, 2.75% N and 1.60% S, and the functional groups on their surface included -OH, -COOH, C[double bond, length as m-dash]C, -NH2 and C[double bond, length as m-dash]O. In vitro and in vivo biodistribution of pizza FNPs was evaluated using normal rat kidney (NRK) cells, onion epidermal cells, Caenorhabditis elegans and mice. The fluorescence microscopy images clearly indicate that the pizza FNPs appear to be localized within the cytoplasm. However, the FNPs remained restricted to the extracellular space of the onion epithelium and did not enter the onion cell cytoplasm because of the cell wall. The FNPs were swallowed by the Caenorhabditis elegans worms when exposed to food OP50 and distributed within the pharynx, intestine and anus. Obvious fluorescence of the FNPs in the stomach, intestine, liver, lung and kidney was observed for the FNPs in mouse organs, but not the brain, heart, and spleen. Furthermore, the produced FNPs were found to cause cell cycle arrest at the G0/G1 phase in NRK cells, and resulted in cell apoptosis at high doses. The outcome of this research offers an important insight into the nature of thermal processing-induced nanoparticles and their in vivo and in vitro biological effects.

Role of protein phosphatase 2A in PTTH-stimulated prothoracic glands of the silkworm, Bombyx mori.

In the present study, the roles of a major serine/threonine protein phosphatase 2A (PP2A) in prothoracicotropic hormone (PTTH)-stimulated prothoracic glands (PGs) of Bombyx mori were evaluated. Immunoblotting analysis showed that Bombyx PGs contained a structural A subunit (A), a regulatory B subunit (B), and a catalytic C subunit (C), with each subunit undergoing development-specific changes. The protein levels of each subunit were not affected by PTTH treatment. However, the highly conserved tyrosine dephosphorylation of PP2A C subunit (PP2Ac), which appears to be related to activity, was increased by PTTH treatment in a time-dependent manner. We further demonstrated that phospholipase C (PLC), Ca2+, and reactive oxygen species (ROS) are upstream signaling for the PTTH-stimulated dephosphorylation of PP2Ac. The determination of PP2A enzymatic activity showed that PP2A enzymatic activity was stimulated by PTTH treatment both in vitro and in vivo. Okadaic acid (OA), a specific PP2A inhibitor, prevented the PTTH-stimulated dephosphorylation of PP2Ac and reduced both basal and PTTH-stimulated PP2A enzymatic activity. The determination of ecdysteroid secretion showed that treatment with OA did not affect basal ecdysteroid secretion but did significantly inhibit PTTH-stimulated ecdysteroid secretion, indicating that PTTH-stimulated PP2A activity is involved in ecdysteroidogenesis. Treatment with OA stimulated the basal phosphorylation of the extracellular signal-regulated kinase (ERK) and 4E-binding protein (4E-BP) without affecting PTTH-stimulated ERK and 4E-BP phosphorylation. From these results, we hypothesize that PTTH-regulated PP2A signaling is a necessary component for the stimulation of ecdysteroidogenesis, potentially by mediating the link between ERK and TOR signaling pathways.

Effects of Thermoextracts of Brucella S and L Forms on Lipid Peroxidation and Antioxidant Defense in Organs of Laboratory Animals.

The dynamics of LPO marker malondialdehyde formation and peroxidase-destroying activity was studied in homogenized organs of guinea pigs, immunized with thermoextracts from S and L forms Brucella abortus I-206. The L form brucella thermoextract exhibited a lower reactogenicity and adequately activated the antioxidant system, due to which the destructive effects of ROS could be partially neutralized during the vaccinal process.

Bioactive extracellular compounds produced by the dinoflagellate Alexandrium minutum are highly detrimental for oysters.

Blooms of the dinoflagellate Alexandrium spp., known as producers of paralytic shellfish toxins (PSTs), are regularly detected on the French coastline. PSTs accumulate into harvested shellfish species, such as the Pacific oyster Crassostrea gigas, and can cause strong disorders to consumers at high doses. The impacts of Alexandrium minutum on C. gigas have often been attributed to its production of PSTs without testing separately the effects of the bioactive extracellular compounds (BECs) with allelopathic, hemolytic, cytotoxic or ichthyotoxic properties, which can also be produced by these algae. The BECs, still uncharacterized, are excreted within the environment thereby impacting not only phytoplankton, zooplankton but also marine invertebrates and fishes, without implicating any PST. The aim of this work was to compare the effects of three strains of A. minutum producing either only PSTs, only BECs, or both PSTs and BECs, on the oyster C. gigas. Behavioral and physiological responses of oysters exposed during 4 days were monitored and showed contrasted behavioral and physiological responses in oysters supposedly depending on produced bioactive substances. The non-PST extracellular-compound-producing strain primarily strongly modified valve-activity behavior of C. gigas and induced hemocyte mobilization within the gills, whereas the PST-producing strain caused inflammatory responses within the digestive gland and disrupted the daily biological rhythm of valve activity behavior. BECs may therefore have a significant harmful effect on the gills, which is one of the first organ in contact with the extracellular substances released in the water by A. minutum. Conversely, the PSTs impact the digestive gland, where they are released and mainly accumulated, after degradation of algal cells during digestion process of bivalves. This study provides a better understanding of the toxicity of A. minutum on oyster and highlights the significant role of BECs in this toxicity calling for further chemical characterization of these substances.

Combined oral contraceptives promote androgen receptor and oestrogen receptor alpha upregulation in the female prostate (Skene's paraurethral glands) of adult gerbils (Meriones unguiculatus).

The aim of this study was to evaluate the effects of cyproterone acetate (CPA) and ethinyloestradiol (EE) alone or in combination on the female prostate of adult gerbils. Adult females were exposed for 21 days to daily oral doses of CPA (1mgkg-1), EE (10µgkg-1) or a combination of CPA and EE. Female prostatic complexes were removed, weighed and subjected to morphological, stereological, immunohistochemical and ultrastructural analyses. CPA treatment caused epithelial atrophy and decreased prostate secretory activity. The EE treatment group showed glandular hyperplasia, a high cell-proliferation index and an increase in androgen and oestrogen receptor α (AR and ERα) immunoreactivity. Combined treatment (CPA+EE) caused adverse effects, such as an increase in cell proliferation, higher AR and ERα immunoreactivity, prostatic intraepithelial neoplasia, cell degeneration and aging. In conclusion, the CPA-only treatment promoted antiandrogenic effects on the female gerbil prostate, whereas EE-only had a potent oestrogenic activity. However, when combined, EE overlapped the effects of CPA, changing the pattern of glandular hormonal regulation and stimulating the development of prostatic lesions in female gerbils.

Thyroid hormone receptor localization in target tissues.

The thyroid hormone receptors, TRα1, TRß1 and other subtypes, are members of the nuclear receptor superfamily that mediate the action of thyroid hormone signaling in numerous tissues to regulate important physiological and developmental processes. Their most well-characterized role is as ligand-dependent transcription factors; TRs bind thyroid hormone response elements in the presence or absence of thyroid hormone to facilitate the expression of target genes. Although primarily residing in the nucleus, TRα1 and TRß1 shuttle rapidly between the nucleus and cytoplasm. We have identified multiple nuclear localization signals and nuclear export signals within TRα1 and TRß1 that interact with importins and exportins, respectively, to mediate translocation across the nuclear envelope. More recently, enigmatic cytoplasmic functions have been ascribed to other TR subtypes, expanding the diversity of the cellular response to thyroid hormone. By integrating data on localization signal motifs, this review provides an overview of the complex interplay between TR's dynamic transport pathways and thyroid hormone signaling activities. We examine the variation in TR subtype response to thyroid hormone signaling, and what is currently known about regulation of the variety of tissue-specific localization patterns, including targeting to the nucleus, the mitochondria and the inner surface of the plasma membrane.

Detergent Lysis of Animal Tissues for Immunoprecipitation.

This protocol details protein extraction from mouse tissues for immunoprecipitation purposes and has been applied for the performance of large-scale immunoprecipitations of target proteins from various tissues for the identification of associated proteins by mass spectroscopy. The key factors in performing a successful immunoprecipitation directly relate to the abundance of target protein in a particular tissue type and whether or not the embryonic, newborn, or adult mouse-derived tissues contain fibrous and other insoluble material. Several tissue types, including lung and liver as well as carcinomas, contain significant amounts of fibrous tissue that can interfere with an immunoprecipitation.

Circadian clock-gastrointestinal peptide interaction in peripheral tissues and the brain.

Food intake and sleep are two mutually exclusive behaviors and both are normally confined to opposing phases of the diurnal cycle. The temporal coordination of behavior and physiology along the 24-h day-night cycle is organized by a network of circadian clocks that orchestrate transcriptional programs controlling cellular physiology. Many of the peptide hormones of the gastrointestinal tract are not only secreted in a circadian fashion, they can also affect circadian clock function in peripheral metabolic tissues and the brain, thus providing metabolic feedback to metabolic and neurobehavioral circuits. In this review, we summarize the current knowledge on this gastrointestinal peptide crosstalk and its potential role in the coordination of nutrition and the maintenance of metabolic homeostasis.

The sex pheromone of a globally invasive honey bee predator, the Asian eusocial hornet, Vespa velutina.

The Asian hornet, Vespa velutina, is an invasive, globally-distributed predator of European honey bees and other insects. To better under its reproductive biology and to find a specific, effective, and low-impact control method for this species, we identified and tested the key compounds in V. velutina sex pheromone. Virgin gynes (reproductive females) produced this sex pheromone in the sixth intersegmental sternal glands of their abdomens. The active compounds were 4-oxo-octanoic acid (4-OOA, 10.4 µg bee-1) and 4-oxo-decanoic acid (4-ODA, 13.3 µg bee-1) at a 0.78 ratio of 4-OOA/4-ODA. We synthesized these compounds and showed that male antennae were highly sensitive to them. Moreover, males were only strongly attracted to a 4-OOA/4-ODA blend at the natural ratio produced by gynes. These results provide the first demonstration of an effective way to lure V. velutina males, and the first chemical identification of a sex pheromone in the eusocial hornets.

Oxidative damage of 18S and 5S ribosomal RNA in digestive gland of mussels exposed to trace metals.

Numerous studies have shown the ability of trace metals to accumulate in marine organisms and cause oxidative stress that leads to perturbations in many important intracellular processes, including protein synthesis. This study is mainly focused on the exploration of structural changes, like base modifications, scissions, and conformational changes, caused in 18S and 5S ribosomal RNA (rRNA) isolated from the mussel Mytilus galloprovincialis exposed to 40µg/L Cu, 30µg/L Hg, or 100µg/L Cd, for 5 or 15days. 18S rRNA and 5S rRNA are components of the small and large ribosomal subunit, respectively, found in complex with ribosomal proteins, translation factors and other auxiliary components (metal ions, toxins etc). 18S rRNA plays crucial roles in all stages of protein synthesis, while 5S rRNA serves as a master signal transducer between several functional regions of 28S rRNA. Therefore, structural changes in these ribosomal constituents could affect the basic functions of ribosomes and hence the normal metabolism of cells. Especially, 18S rRNA along with ribosomal proteins forms the decoding centre that ensures the correct codon-anticodon pairing. As exemplified by ELISA, primer extension analysis and DMS footprinting analysis, each metal caused oxidative damage to rRNA, depending on the nature of metal ion and the duration of exposure. Interestingly, exposure of mussels to Cu or Hg caused structural alterations in 5S rRNA, localized in paired regions and within loops A, B, C, and E, leading to a continuous progressive loss of the 5S RNA structural integrity. In contrast, structural impairments of 5S rRNA in mussels exposed to Cd were accumulating for the initial 5days, and then progressively decreased to almost the normal level by day 15, probably due to the parallel elevation of metallothionein content that depletes the pools of free Cd. Regions of interest in 18S rRNA, such as the decoding centre, sites implicated in the binding of tRNAs (A- and P-sites) or translation factors, and areas related to translation fidelity, were found to undergo significant metal-induced conformational alterations, leading either to loosening of their structure or to more compact folding. These modifications were associated with parallel alterations in the translation process at multiple levels, a fact suggesting that structural perturbations in ribosomes, caused by metals, pose significant hurdles in translational efficiency and fidelity.

Glue protein production can be triggered by steroid hormone signaling independent of the developmental program in Drosophila melanogaster.

Steroid hormones regulate life stage transitions, allowing animals to appropriately follow a developmental timeline. During insect development, the steroid hormone ecdysone is synthesized and released in a regulated manner by the prothoracic gland (PG) and then hydroxylated to the active molting hormone, 20-hydroxyecdysone (20E), in peripheral tissues. We manipulated ecdysteroid titers, through temporally controlled over-expression of the ecdysteroid-inactivating enzyme, CYP18A1, in the PG using the GeneSwitch-GAL4 system in the fruit fly Drosophila melanogaster. We monitored expression of a 20E-inducible glue protein gene, Salivary gland secretion 3 (Sgs3), using a Sgs3:GFP fusion transgene. In wild type larvae, Sgs3-GFP expression is activated at the midpoint of the third larval instar stage in response to the rising endogenous level of 20E. By first knocking down endogenous 20E levels during larval development and then feeding 20E to these larvae at various stages, we found that Sgs3-GFP expression could be triggered at an inappropriate developmental stage after a certain time lag. This stage-precocious activation of Sgs3 required expression of the Broad-complex, similar to normal Sgs3 developmental regulation, and a small level of nutritional input. We suggest that these studies provide evidence for a tissue-autonomic regulatory system for a metamorphic event independent from the primary 20E driven developmental progression.

In vivo biodistribution and toxicity of intravesical administration of quantum dots for optical molecular imaging of bladder cancer.

Optical molecular imaging holds the potential to improve cancer diagnosis. Fluorescent nanoparticles such as quantum dots (QD) offer superior optical characteristics compared to organic dyes, but their in vivo application is limited by potential toxicity from systemic administration. Topical administration provides an attractive route for targeted nanoparticles with the possibility of minimizing exposure and reduced dose. Previously, we demonstrated successful ex vivo endoscopic imaging of human bladder cancer by topical (i.e. intravesical) administration of QD-conjugated anti-CD47. Herein we investigate in vivo biodistribution and toxicity of intravesically instilled free QD and anti-CD47-QD in mice. In vivo biodistribution of anti-CD47-QD was assessed with inductively coupled plasma mass spectrometry. Local and systemic toxicity was assessed using blood tests, organ weights, and histology. On average, there was no significant accumulation of QD outside of the bladder, although in some mice we detected extravesical biodistribution of QD suggesting a route for systemic exposure under some conditions. There were no indications of acute toxicity up to 7 days after instillation. Intravesical administration of targeted nanoparticles can reduce systemic exposure, but for clinical use, nanoparticles with established biosafety profiles should be used to decrease long-term toxicity in cases where systemic exposure occurs.

Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling.

Fluorescence-mediated tomography (FMT) is a quantitative three-dimensional imaging technique for preclinical research applications. The combination with micro-computed tomography (µCT) enables improved reconstruction and analysis. The aim of this study is to assess the potential of µCT-FMT and kinetic modeling to determine elimination and retention of typical model drugs and drug delivery systems. We selected four fluorescent probes with different but well-known biodistribution and elimination routes: Indocyanine green (ICG), hydroxyapatite-binding OsteoSense (OS), biodegradable nanogels (NG) and microbubbles (MB). µCT-FMT scans were performed in twenty BALB/c nude mice (5 per group) at 0.25, 2, 4, 8, 24, 48 and 72 h after intravenous injection. Longitudinal organ curves were determined using interactive organ segmentation software and a pharmacokinetic whole-body model was implemented and applied to compute physiological parameters describing elimination and retention. ICG demonstrated high initial hepatic uptake which decreased rapidly while intestinal accumulation appeared for around 8 hours which is in line with the known direct uptake by hepatocytes followed by hepatobiliary elimination. Complete clearance from the body was observed at 48 h. NG showed similar but slower hepatobiliary elimination because these nanoparticles require degradation before elimination can take place. OS was strongly located in the bones in addition to high signal in the bladder at 0.25 h indicating fast renal excretion. MB showed longest retention in liver and spleen and low signal in the kidneys likely caused by renal elimination or retention of fragments. Furthermore, probe retention was found in liver (MB, NG and OS), spleen (MB) and kidneys (MB and NG) at 72 h which was confirmed by ex vivo data. The kinetic model enabled robust extraction of physiological parameters from the organ curves. In summary, µCT-FMT and kinetic modeling enable differentiation of hepatobiliary and renal elimination routes and allow for the noninvasive assessment of retention sites in relevant organs including liver, kidney, bone and spleen.