Iridophoroma associated with the Lemon Frost colour morph of the leopard gecko (Eublepharis macularius).

The Lemon Frost is a new colour morph of the leopard gecko, which emerged in ca. 2015 as a result of selective breeding and spontaneous mutation. According to multiple breeders observation of Lemon Frost inbreeding with wild-type leopard geckos, Lemon Frost seems to be a codominant trait. Additionally breeders observed another, presumably associated trait - tumour-like skin lesions. Three private-owned Lemon Frost morph leopard geckos with tumour-like skin lesions were admitted to our clinic for examination, which included histopathology, X-ray and ultrasonography. The histopathological investigation of the biopsies indicated malignant iridophoroma; however, no changes were observed in diagnostic imaging. This research is the first report of clinical and histopathological findings of iridophoroma in leopard geckos.

Fatal pulmonary hemorrhage in a horse during bronchoalveolar lavage - single case report.

BACKGROUND: Pulmonary hemorrhage is a rare cause of death in horses. Hemorrhage within the respiratory tract has many causes, including mycosis of the guttural pouch, invasive procedures causing serious trauma to nasal conchae, or lung biopsy. We report on a rare case of a fatal pulmonary hemorrhage in a horse after a severe cough during bronchoalveolar lavage. To the best of our knowledge, this is the first report of spontaneous hemorrhage in a horse during bronchoalveolar lavage. CASE PRESENTATION: A 21-year-old mare which belonged to the didactic herd of The Faculty of Veterinary Medicine underwent BAL procedure for training purposes. Clinical examination prior to the procedure did not reveal any abnormalities and the horse had been classified as healthy. The horse was sedated with 0.01 mg/kg of detomidine and 0.01 mg/kg of butorphanol. The silicon BAL catheter was passed through the nasal passage into the trachea and then into the bronchus. Before catheter was wedged, the mare began to cough heavily and massive haemorrhage from mouth and nostrils occurred. Despite fluid therapy, shock occurred within 15 min and the mare was euthanized. Upon necropsy, site of hemorrhage was identified in the left lobar caudal bronchi, from a large blood vessel running directly beneath the bronchial wall. Upon histology, a chronic lympho-plasmocytic inflammatory process in left bronchi was identified. Moreover, Masson's trichrome staining revealed severe, perivascular fibrosis. CONCLUSION: Although BAL is a relatively safe procedure, and such complications should be treated as extremely rare, this case indicates that, in some individuals with specific subclinical problems, even mild physical force such as a cough can lead to rupture of the artery.

Reconstruction of cranial cruciate ligament in rabbits using polyester implants saturated with PRP, antlerogenic stem cells MIC-1 and their homogenate.

AIM OF THE STUDY: The attempt to limit the negative effects of polyester implants on the articular cavity by using preparations containing growth factors. MATERIALS AND METHODS: Polyester implants used for the reconstruction of a rabbit's cranial cruciate ligament (CCL) were saturated with autogenic platelet-rich plasma (PRP), antlerogenic stem cells MIC-1 and their homogenate prior to the surgery. Six months after CCL reconstruction, morphological, and biochemical blood tests were carried out, including proteinogram and acute phase proteins. The knee joints were also examined macro- and microscopically. RESULTS: The results, compared to the control group, showed a favorable effect of the PRP and homogenate of antlerogenic cells on limiting the inflammation caused by the presence of polyester implant in the knee joint. The addition of growth factors caused covering the implant faster with the recipient's connective tissue, thus contributing to reducing the inflammatory reaction of the articular capsule to the presence of polyester. At the same time, no enhanced local or general reaction of the rabbit organism was observed to the presence of xenogenic antlerogenic stem cells MIC-1 homogenate which, like the PRP, may provide an easily available source of growth factors, increasingly often used in regenerative medicine. CONCLUSIONS: Applying antlerogenic stem cells, their homogenate or PRP increases the volume of connective tissue that surrounds and intertwines polyester CCL implant, separating it from synovial cavity environment.

Histopathological pattern of gonads in cases of sex abnormalities in dogs: An attempt of morphological evaluation involving potential for neoplasia.

Disturbances in sex differentiation (DSD - disorder of sexual development) may result from disturbances in sex chromosomes or a disturbed development of gonads, or from genotypic disturbances. The objective of this article is to describe the histological structure of gonads in dogs showing sexual disturbances and a case of a cancer resembling gonadoblastoma in one of the animals. Among the 10 examined dogs with disturbances of sex development only a single case of a gonadoblastoma was observed. In animals with sex disturbances, similarly to humans, there exists a potential tendency for neoplastic lesions in dysgenetic gonads. As a rule, its frequency in population is confined due to the early procedure of castration of non-breeding dogs. In the present study dogs demonstrated phenotypical traits of bitches with developmental anomalies such as hyperplastic clitoris with vestigial os penis (baculum), or abnormalities in the location and structure of the vulva. The material for the study included canine gonads of various breeds, sampled from phenotypical bitches, aged 7 months to 4 years - patients of the Department of Reproduction and Clinic of Farm Animals, Faculty of Veterinary Medicine, University of Environmental and Life Sciences in Wroclaw (Poland) in years 2006-2013. The organs were surgically removed from the abdomen and sent for histopathological examination for the purpose of determining their histological structure. The 10 examined cases of altered gonads included 6 bilateral cases of testes (60%), 2 cases of bilateral ovotestis (20%), one case of co-manifestation of testis and ovotestis (10%), and a single case of a testis and a neoplastically altered gonad (gonadoblastoma) (10%).

Useful immunohistochemical indicators in canine mast cell tumours.

Morphological and immunohistochemical analysis of 45 canine mast cell tumours was performed to determine whether the proteins examined are useful for a more precise description of tumour morphology and a more reliable determination of the prognosis in patients. Tissue sections were stained according to the standard haematoxylin and eosin (HE) technique and with toluidine blue to demonstrate cytoplasmic granules. Immunohistochemical studies were performed, using the cell markers CD117 (c-kit), p16 and von Willebrand factor (FVIII). In CD117 three different staining patterns were observed: (1) membranous reaction, (2) intense staining of cytoplasm, and (3) a diffuse, delicate cytoplasmic reaction. Von Willebrand antibody was evaluated on the basis of the number of blood vessels stained. p16 expression was evaluated by scoring positive nuclear reaction. Positive expression was demonstrated for all examined antigens, but their level of expression differed depending on the grades of tumour malignancy. Statistical analysis of the results documented a pronounced positive correlation between the markers studied and the grade of tumour malignancy (P < 0.001). It was shown that each of the cell markers examined represents a useful prognostic indicator for patients with mast cell tumours. The calculated correlation coefficients demonstrate a strong association between the expressions of CD117, FVIII and p16, and the histological malignancy of a tumour.

Expression of matrix metalloproteinase 2 (MMP-2), E-cadherin and Ki-67 in metastatic and non-metastatic canine mammary carcinomas.

BACKGROUND: The aim of the study was to demonstrate the immunohistochemical expression of proteins that affect the metastatic potential of a tumour, including matrix metalloproteinase 2 (MMP-2) and E-cadherin. Another objective was to determine their correlation with the expression of the Ki-67 antigen in metastasizing and non-metastasizing mammary carcinomas in female dogs. The study was conducted on 32 canine mammary carcinomas (12 metastatic and 20 non-metastatic), classified as simple tubular and tubulopapillary carcinomas. Immunohistochemistry was performed to evaluate the expression of MMP-2, E-cadherin and Ki-67 antigen. RESULTS: MMP-2 was expressed in 85 % of the non-metastatic tumours and in all the metastatic tumours, while E-cadherin was expressed in 85 % of the non-metastatic tumours and in 66 % of the metastatic tumours. The Ki-67 antigen was expressed in 65 % of the non-metastatic tumours and in 91 % of the metastatic tumours. The mean Ki-67 expression was slightly higher in tumours that had metastasized (1.5 ± 0.90 vs 1.1 ± 0.94; p = 0.22). A similar relationship was found in terms of the intensity of the MMP-2 expression (2.9 ± 1.9 vs 2.7 ± 2.4; p = 0.50). A decrease in the expression of E-cadherin (2.8 ± 2.5) was found in metastatic tumours compared to the expression in non-metastatic tumours (3.2 ± 2.3). However, these differences were not statistically significant (p = 0.63). CONCLUSION: We did not show significant differences in MMP-2, E-cadherin and Ki-67 expression between metastatic and non-metastatic tumours due to low number of cases studied, however further experiments are necessary to assess the role of these antigens in the process of canine mammary tumours metastasis.

Inhibin-α, E-cadherin, calretinin and Ki-67 antigen in the immunohistochemical evaluation of canine and human testicular neoplasms.

INTRODUCTION: The steady increase of dogs with diagnosed testicular neoplasms observed in recent years prompted us to carry out immunohistochemical (IHC) studies for their better characterization. The aim of the study was to analyze most common canine testicular neoplasms (seminomas, Leydig cell and Sertoli cell tumors) with selected IHC markers and to compare the expressions of these proteins in corresponding canine and human testicular tumors. MATERIAL AND METHODS: Studies were carried out on testicular canine tumors: 40 cases of seminoma, 40 cases of Leydig cell tumor and 40 cases of Sertoli cell tumor. Moreover, 15 cases of human seminomas and 5 cases of human Leydig cell tumors were also analyzed. Immunohistochemistry was performed on paraffin sections by standard technique using monoclonal anti-human antibodies against E-cadherin, inhibin-α, calretinin and Ki-67. The slides were subjected to computer-aided image analysis and the intensity of the immunoreactivity was assessed by a semi-quantitative scoring system. RESULTS: Due to the very low prevalence of the Sertoli cell-derived tumors in the human population, we were able to examine the markers' expression only in the canine gonadal tumors. We revealed that, apart from E-cadherin in Leydig cell tumors and calretinin in seminomas, the expression of all the analyzed markers in canine and human testicular tumors was similar. E.g. there was no immunoexpression of inhibin-α in 75% of canine and 100% of human cases of seminoma. The immunoreactivity of Ki-67 was intense in 40% of canine and 60% of human seminomas. Immunoexpression of inhibin-α in Leydig cell tumor was intense in 70% of canine and 100% of human cases, respectively. Also the immunoreactivity of calretinin was intense in 75% of cases of canine and 100% of human Leydig cell tumors. In 50% of canine and 40% of human Leydig cell tumors, the immunoexpression of Ki-67 was weak. CONCLUSIONS: The applied anti-human monoclonal antibodies against common antigens and markers of human testicular neoplasms could be routinely used for the immunohistochemical evaluation of canine testicular tumors.

Expression of hypoxia-inducible factor-1α and vascular density in mammary adenomas and adenocarcinomas in bitches.

BACKGROUND: The study aimed at examining hypoxia-inducible factor (HIF)1α expression in adenocarcinomas and adenomas in bitches in regard to tumour malignancy grade, proliferation, apoptosis and vascularisation. Therefore, paraffin sections of 15 adenomas and 64 adenocarcinomas sampled from 79 dogs aged 6 to 16 years were analysed. RESULTS: A significantly higher HIF-1α expression was noted in adenocarcinomas in comparison to adenomas (P < 0.0004). Moreover, HIF-1α expression in adenocarcinomas correlated positively with tumour malignancy grade (r = 0.59, P < 0.05), Ki-67 antigen expression (r = 0.43; P < 0.0005), TUNEL-positive cells (r = 0.62, P < 0001) and tumour vascularity measured by quantification of vessels characterized by the expression of von Willebrand Factor (r = 0.57, P < 0.05). CONCLUSION: Results of this study indicate a similar biological role of HIF-1α in dogs and in humans, which may confirm suitability of the animal model in investigations on progression of tumours in humans.

Ceramide galactosyltransferase (UGT8) as a molecular marker of canine mammary tumor malignancy.

Thirty-two canine mammary tubulopapillary carcinomas and 14 simple adenomas were studied by immunohistochemistry for the expression of UDP-galactose:ceramide galactosyltransferase (UGT8). The majority of tissue specimens (57%) representing adenomas had no or weak reaction with anti-UGT8 antibodies (0-2 pts according to IRS scale) in comparison to the majority of carcinomas (90%) which stained with high intensities (3-9 pts according to IRS scale). When the average values of the reaction intensities (IRS) for malignant and benign tumors were compared, using the Mann-Whitney U-test, significant differences in UGT8 expression between them were found (P < 0.001). Mammary tubulopapillary carcinomas were further analyzed by IHC and the same rabbit polyclonal antibody directed against UGT8 according to their malignancy grade. It was found that the level of UGT8 increased in tumor specimens together with their grading. A comparison of the average values of the reaction intensity (IRS scale) revealed a significant difference (Mann-Whitney U-test, P < 0.05) in UGT8 expression between tumors representing malignancy grades G3 and G1. Based on the obtained results, it is proposed that UGT8 is associated with malignancy of canine mammary gland cells and may have a potential value as a diagnostic marker.

Expression of Breast Cancer Resistance Protein (BCRP-1) in canine mammary adenocarcinomas and adenomas.

BACKGROUND: Among the recognized factors which induce multi-drug resistance, an increased activity of proteins belonging to the ATP-binding casette family, including breast cancer resistance protein 1 (BCRP-1), is regarded as the most important. Localization and intensity of BCRP-1 expression was evaluated in mammary adenocarcinomas and adenomas in dogs. The obtained results were compared to the grade of malignancy (G) of the tumours. MATERIALS AND METHODS: Materials for the study were sampled in the course of surgery from 54 dogs, of various breeds, aged 6 to 16 years (36 cases of mammary adenocarcinoma and 18 cases of mammary adenoma). The tumours were histopathologically verified and immunohistochemical reactions were performed to evaluate expression of BCRP-1. The microscopic patterns were photographed and subjected to computer-assisted analysis taking advantage of MultiScanBase Ver. 14.02 software. RESULTS: Expression of BCRP-1 was detected in over 85% of adenocarcinomas and almost 28% of adenomas. Samples of tumours with a higher grade of malignancy demonstrated an increased expression of BCRP-1. The two variables manifested a moderate positive correlation (r=0.35; p<0.05). CONCLUSION: The results point to a role of BCRP-1 protein in biology of tumour cells in dogs.

Correlation between MCM-3 protein expression and grade of malignancy in mammary adenocarcinomas and soft tissue fibrosarcomas in dogs.

BACKGROUND: Minichromosome maintenance proteins (MCM), due to their involvement in DNA replication in the course of mitosis, may provide sensitive markers of cell proliferation. Localization of MCM-3 and the extent of its expression were evaluated in mammary adenocarcinomas and soft tissue fibrosarcomas in dogs. The obtained results were compared to grades of malignancy (G) of the studied tumours. MATERIALS AND METHODS: The research material was sampled in the course of surgery in 71 dogs of various breeds, aged 4 to 14 years (50 cases of mammary adenocarcinoma and 21 cases of soft tissue fibrosarcoma). The tumours were verified by histopathology and immunohistochemistry was used to evaluate MCM-3 expression. The preparations were photographed and the images were subjected to computer-assisted image analysis using MultiScanBase Ver. 14.02 software. RESULTS: Nuclear expression of MCM-3 was detected in 70% adenocarcinomas and in over 71% of fibrosarcomas. Augmented expression of MCM-3 was observed in samples of tumours manifesting higher grade of malignancy. Statistical analysis demonstrated strong positive correlation (r=0.71 for fibrosarcomas, r=0.52 for adenocarcinomas; p<0.05) between MCM-3 expression and grade of malignancy in the studied tumours. CONCLUSION: MCM-3 may provide a sensitive and useful marker of proliferative potential in various histological types of neoplastic tumours.

The influence of 1,25-dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 on alphavbeta3 integrin expression in cancer cell lines.

Integrins are cell-surface receptors engaged in important cancer invasion processes, such as adhesion, migration, proliferation and differentiation. The aim of this study was to evaluate the effect of 1,25-dihydroxyvitamin D3 (calcitriol) and its metabolite 1,24-dihydroxyvitamin D3 (PRI-2191) on alphavbeta3 integrin expression in various cancer cell lines. The expression levels of the beta3 and alphav integrins were reduced only in the WEHI-3 and LLC cell lines by the two compounds. Calcitriol or PRI-2191 treatment caused differentiation of WEHI-3 mouse leukemia cells, but apoptosis of LLC cells. WEHI-3 and LLC cells exposed to calcitriol or PRI-2191 lost their migratory and adhesive potentials. The inhibition of migratory potential was higher in the LLC cells than in the WEHI-3 cells and appeared to correlate with the increased down-regulation of alphavbeta3 integrin by calcitriol or PRI-2191. The observed in vivo effects (antitumor and antimetastatic) in mice bearing subcutaneously transplanted LLC cancer are possibly associated with inhibited migratory potential as a consequence of the lowered integrin expression caused by calcitriol or PRI-2191.

Expression of extracellular matrix metalloproteinase (MMP-9), E-cadherin and proliferation-associated antigen Ki-67 and their reciprocal correlation in canine mammary adenocarcinomas.

BACKGROUND: The purpose of the present study was to determine the expression of the proteins related to tumour metastatic potential, including matrix metalloproteinase (MMP)-9 and E-cadherin, in correlation with the expression of proliferation-associated antigen (Ki-67) in canine mammary adenocarcinomas. MATERIALS AND METHODS: Material for the studies was obtained during surgery from 35 dogs of various breeds, aged 7 to 16 years. Neoplastic tumours were verified by a pathologist. The studied proteins were detected by immunohistochemical reactions. The microphotographs of the studied tumours were subjected to computer-assisted image analysis using MultiScaneBase V 14.02 software. RESULTS: Expression of MMP-9 was noted in almost 83% of the tumours, expression of E-cadherin in 77% of tumours, while expression of Ki-67 antigen was detected in fewer than 26% of studied tumours. CONCLUSION: The positive correlation (r=0.375) between expressions of MMP-9 and Ki-67 and negative correlations between E-cadherin and Ki-67 (r=-0.383) as well as between MMP-9 and E-cadherin (r=-0.45) could suggest that expression and biological significance of the studied markers in mammary adenocarcinomas in dogs resembles the pattern noted in ductal carcinoma, i.e. in the most frequent histological type of malignant tumour in humans. This may point to suitability of the animal model in studies on mechanism of neoplasia and metastases in humans.

Immunohistochemical localization of telomerase in myomas and in uterine myometrium.

Telomerase activity could be a potential marker for the neoplastic process, because it is absent in normal cells and present in tumor cells. Immunohistochemical studies were conducted using samples obtained from 32 uterine myomas, each sample having a size of 3-4 cm and obtained from women between 35 and 45 years of age. These studies also concentrated on fragments of macroscopically unaltered myometrium, collected 3-4 cm from a uterine tumor. Immunohistochemistry was performed using antibody to the catalytic unit of telomerase (hTERT; clone 44F12, NCL-L-hTERT, Novocastra Laboratories, UK). This study aimed at detecting a possible presence of potentially neoplastic cells in the margins of healthy tissue, which was removed together with the primary tumor. The results were classified according to the number of telomerase-positive cells. Tumors of the first group had up to 50% telomerase-positive cells, while their content in the second group exceeded 50%. Our study demonstrated an almost two-fold increase in the number of telomerase-positive tumor cells compared with myometrial cells 3-4 cm from the tumor. Hopefully, investigating the presence of telomerase in both uterine myometrium and myoma could facilitate the diagnosis of the neoplastic process.

Liposomal formulation of 5-fluorocytosine in suicide gene therapy with cytosine deaminase--for colorectal cancer.

It is generally accepted that successful gene therapy depends on two major factors: tumor-specific expression of a therapeutic gene and the efficient transfer of a therapeutic gene to tumor cells. For gene-directed enzyme prodrug therapy (GDEPT) involving Escherichia coli cytosine deaminase (CD) and 5-fluorocytosine (5-FC), several tumor-specific promoters and virus-based vectors were used. No attention whatsoever was paid to the way of 5-FC delivery to solid tumors, despite the fact that the delivery of drugs to such tumors is generally low because of their insufficient transfer from the blood. To compare the effectiveness of GDEPT with free and liposomal 5-FC, the prodrug was encapsulated in liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and cholesterol (1:1). When the liposomal form of 5-FC was administered i.v., mice treated with a dose of 5mg of liposomal 5-FC/kg body weight for 10 days, showed complete regression of transplanted tumors and complete cure was observed, whereas in animals treated with the same amounts of the free prodrug, 50% tumor regression and only insignificantly prolonged median survival were found. In summary, these results showed a remarkable enhancement of the antitumor effects of the liposomal form of 5-FC in comparison with the free prodrug. Therapy with liposomal 5-FC thus represents a new approach to achieving a high local concentration of the prodrug for suicide gene therapy using E. coli CD.

Expression of E-cadherin, beta-catenin and Ki-67 antigen and their reciprocal correlations in fibrosarcomas of soft tissues in dogs.

BACKGROUND: This study aimed at immunocytochemical demonstration of E-cadherin, beta-catenin and Ki-67 expressions and the examination of correlation between these markers in primary fibrosarcomas in dogs. MATERIALS AND METHODS: Material for the study was sampled in the course of surgery from 24 mongrel dogs aged 5 to 16 years. The neoplastic tumors were subjected to histopathological verification and immunohistochemical reactions were performed to detect the studied markers. Microphotographs of the preparations were subjected to computer-assisted image analysis using the MultiScaneBase V 14.02 software. RESULTS: Expression of beta-catenin was detected in all tumours examined while E-cadherin was expressed in only 8.2%. Expression of the Ki-67 proliferation-associated antigen was noted in over 33% of the tumours. CONCLUSION: The lack of correlation (r=-0.1035) between expression of Ki-67 and that of beta-catenin detected here in contrast to the high values of Ki-67 antigen found as a prognostic factor in many other studies allowed us to conclude that the presence of beta-catenin in cells of soft tissue fibrosarcoma in dogs manifested no unequivocal relationship to augmented proliferative potential of neoplastic cells, although it did not exclude participation of the protein in the development of this neoplasia in dogs.

Expression of E-cadherin, beta-catenin and Ki-67 antigen and their reciprocal relationships in mammary adenocarcinomas in bitches.

In progression of tumours, resulting from, i.e., release of cells from the parental tumour and development of metastases, expression of cell adhesion molecules (CAM) plays a significant role. CAM, including E-cadherin and the linked to it beta-catenin, determine the extent of adhesion between normal and neoplastically altered cells. Moreover, the unbound form of beta-catenin in a cell nucleus may affect the rate of cell proliferation This study aimed at demonstrating intensity and localisation of E-cadherin and beta-catenin expression as related to expression of the proliferation-associated antigen, Ki-67 in mammary adenocarcinomas of bitches. The study was performed on 35 cases of the above mentioned tumours. On paraffin sections immunohistochemical reactions were performed using monoclonal antibodies directed against E-cadherin, beta-catenin and Ki-67 antigen. In the studies a membranous expression of E-cadherin, a cytoplasmic-nuclear expression of beta-catenin and nuclear expression of Ki-67 antigen were demonstrated. Statistical calculations using Spearman's test demonstrated a pronounced positive correlation between expression of beta-catenin and Ki-67 antigen and absence of correlation between expression of E-cadherin and Ki-67 antigen. No correlation could be detected between expression intensities of E-cadherin and beta-catenin.

Ozone therapy in induced endotoxemic shock. II. The effect of ozone therapy upon selected histochemical reactions in organs of rats in endotoxemic shock.

Mitochondria and lysosomes were evaluated by assessment of changes in activity of selected enzymes: lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), adenosinetriphosphatase (ATPase), acid phosphatase (AcPase) and beta-glucuronidase (BG) in rats under profound hypoxia induced by endotoxemic shock. The study was conducted on adult male Wistar rats. The animals formed the following four groups of 15 rats each: control animals (C);-rats receiving intraperitonally O(2)/O(3) (CO), rats receiving of Escherichia coli toxin (LPS) (CL); rats receiving LPS plus oxygen-ozone mixture (OL). Histoenzymatic examinations of liver, kidney, lungs, and heart muscle were performed. Lipopolysaccharide suppressed activities of all the enzymes except for LDH, the activity of which as high as a fourfold increase. The results demonstrated potent, stabilizing and regenerative effects of ozone therapy on body enzymatic processes in course of induced endotoxemic shock in rats, which might prove to be of clinical significance.

Ozonotherapy in an induced septic shock. I. Effect of ozonotherapy on rat organs in evaluation of free radical reactions and selected enzymatic systems.

The confirmed advantageous effects of oxygen/ozone therapy in several clinical conditions stimulated experimental studies on effects of the therapy in rats with an induced septic shock. The studies were conducted on adult male rats of Wistar strain. Four groups of the animals, each of 15 rats, included: I--control group, (C); II--animals intraperitoneally administered with O(2)/O(3) (CO), III--rats given of Escherichia coli endotoxin (lipopolysaccharide-LPS) (CL), IV--rats administered with the lipopolysaccharide plus administered with the oxygen/ozone mixture (OL). Activities of catalase and superoxide dismutase and of free radical reactions were estimated. The exposure to LPS augmented activities of SOD and of catalase in liver, lungs and heart. In all the examined organs LPS induced significant changes in levels of free radicals. Except of the lungs, parallel administration of the rats with LPS and ozone/oxygen revoked development of the alterations. The obtained results point to a strong, stabilizing and regenerative effect of ozonotherapy.