Teriflunomide induces Foxp3 expression in murine CD8 + T cells while IL-27 and retinoic acid exert a synergistic effect on the induction of CD39 expression on these cells.

The purpose of this study was to verify the possibility of pharmacological induction of Foxp3 +CD25 +CD8 + and Foxp3 -CD103 +CD8 + T regulatory cells 'armed' with immunosuppressive molecules, i.e. CD39 and IL-10. To achieve this purpose, stimulated and unstimulated murine lymphocytes were exposed to IL-27, teriflunomide (TER) and all trans retinoic acid (ATRA). The study found that: (a) IL-27 induced CD39 expression on Foxp3 +CD25 +CD8 + T cells and the ability of CD103+Foxp3-CD8+ T cells to produce IL-10 as well as increasing the absolute number of IL-10 +CD103 +Foxp3 -CD8 + T cells; (b) TER induced Foxp3 expression in CD25+CD8+ T cells and CD103 expression on Foxp3 -CD8 + T cells as well as increasing the absolute number of Foxp3 +CD25 +CD8 + T cells; (c) ATRA induced the capacity of Foxp3 +CD25 +CD8 + T cells to produce IL-10. The following desired interactions were demonstrated between IL-27 and ATRA: (a) a strong synergistic effect with respect to increasing CD39 expression and the ability to produce IL-10 by Foxp3 +CD25 +CD8 + T cells; (b) a synergistic effect with respect to increasing the absolute count of CD39 +Foxp3 +CD25 +CD8 + T cells. The study revealed that TER abolished all these effects. Therefore, a combination of the tested agents did not induce the generation of Foxp3 +CD25 +CD8 + and Foxp3 -CD103+CD8+ T cells characterized by extensive CD39 expression and IL-10 production. Thus, in the context of the pharmacological induction of IL-10 +CD39 +Foxp3 +CD25 +CD8 + and IL-10 +CD103 +Foxp3 -CD8 + T cells, these findings strongly suggest that a combination of TER with IL-27 and/or ATRA does not provide any benefits over TER alone; moreover, such a combination may result in abolishing the desired effects exerted by IL-27 and/or ATRA.

Depletion of T and B cells in lymphoid tissues of mice induced by oclacitinib, a Janus kinase inhibitor.

The main purpose of the study was to determine the safety of oclacitinib (OCL), a Janus kinase inhibitor, with respect of its effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. The mice were treated orally with OCL at a dose of 2.7 mg/kg for 14 days and peripheral blood, head and neck lymph nodes (HNLNs), mediastinal lymph nodes (MLNs) and spleen were collected. The study found that OCL induced depletion of CD4 + T cells in the HNLNs and MLNs, while it did not affect the absolute count of CD8 + T cells in these tissues. Also OCL caused a loss of B cells in the HNLNs, although not in the MLNs. Moreover, OCL depleted B cells in the peripheral blood, but did not affect the absolute count of CD4 + and CD8 + T cells. Thus, it can be concluded that OCL may induce a depletive effect on CD4 + and CD8 + T cells as well as B cells in the lymphoid tissue. This effect should be seen as an unfavorable one, especially in patients with infections. Therefore, a clinical implication is that in such patients, the benefit/risk ratio should be thoroughly considered by clinicians. Moreover, OCL reduced the absolute count of eosinophils, basophils, neutrophils and monocytes. However, it is uncertain whether this effect should be considered to be of clinical importance because the levels of these cells were within the physiological range. It is possible that the depletive effect of OCL toward T and B cells, as well as eosinophils and basophils may contribute to the beneficial effects of the drug in the treatment of skin allergic diseases.

Hard water may increase the inhibitory effect of feed on the oral bioavailability of oxytetracycline in broiler chickens.

The aim of this study was to determine to what extent the ions present in hard water (125 mg/L of MgCl2 and 500 mg/L of CaCl2) may intensify the feed-induced decrease in oxytetracycline (OTC) absorption rate in broiler chickens after single oral administration at a dose of 15 mg/kg. Drug concentrations in plasma were determined by liquid chromatography-tandem mass spectrometry and combined, compartmental and non-compartmental approach was used to assess OTC pharmacokinetics. The administration of feed decreased the absolute bioavailability (F) of OTC from 12.70%±4.01 to 6.40%±1.08, and this effect was more pronounced after the combined administration of OTC with feed and hard water (5.31%±0.90). A decrease in the area under the concentration- time curve (AUC0-t), (from 10.18±3.24 µg·h/ml in control to 5.13 µg·h/ml±1.26 for feed and 4.26 µg·h/ml±1.10 for feed and hard water) and the maximum plasma concentration of OTC (Cmax) (from 1.22±0.18 µg/ml in control, to 1.01 µg/ml ±0.10 for hard water, 0.68 µg/ml±0.10 for feed and 0.61 µg/ml±0.10 for feed and hard water) was observed. The results of this study indicate that feed strongly decreases F, AUC0-t and Cmax of orally administered OTC. The ions present in hard water increase this inhibitory effect, which suggests that, therapy with OTC may require taking into account local water quality and dose modification, particularly when dealing with outbreaks caused by less sensitive microorganisms.

CD4- and CD8-expressing cells found in the bovine and porcine anterior chamber of the eye.

The aim of the present study was to investigate whether the anterior chamber constitutes part of the normal migratory pathway of CD4+ and CD8+ lymphocytes in cattle and swine. The cells obtained from aqueous humor of cows and pigs were stained for CD4 and CD8 receptors, and subsequently analyzed with flow cytometry. The mean percentage of CD4+CD8-, CD4-CD8+ and CD4+CD8+ cells within the total lymphocyte population of the bovine anterior chamber was, respectively, 17.88, 12.64 and 27.26%. In turn, the mean values of these parameters in pigs were 1.77, 38.48 and 17.45, respectively. Among bovine and porcine CD4+CD8+ cells prevalent were those displaying CD4lowCD8low and CD4lowCD8high phenotypes, respectively. The results suggest that the anterior chamber in cattle and swine is an element in the normal migratory pathway of CD4+, CD8+ and CD4+CD8+ cells. Furthermore, the contribution of these subsets in the anterior chamber lymphocyte population can differ considerably between animal species.

Effect of tigecycline on the production of selected cytokines and counts of murine CD4+ and CD8+ T cells - an in vitro study.

Due to the unrecognized effect of tigecycline (TIG) on CD4+ and CD8+ T cells, the present study has been undertaken in order to determine whether the drug can affect these cells in respect of their counts, and the production of IFN-γ, IL-17 (pro-inflammatory and immune-protective cytokines), IL-4 (anti-inflammatory and immune-protective cytokine), IL-10 and TGF-ß (anti-inflammatory and immune-suppressive cytokines). Murine lymphocytes were treated with TIG for 48 and 96 h at concentrations reflecting its plasma levels obtained in vivo at therapeutic doses, and at 10-fold lower concentrations. It was found that TIG neither affected substantially the percentage and absolute counts of entire CD4+ and CD8+ T cell populations nor influenced the Foxp3+CD25+CD4+ regulatory/suppressive T cell subset. Furthermore, the percentages of IL-4-, IL-10-, IL-17- and TGF-ß-producing CD4+ T cells were not altered following the exposure to TIG. Similarly, TIG did not influence IFN-γ production by CD8+ T cells. Thus, with respect to the parameters evaluated, TIG does not seem to exert immune-suppressive and anti-inflammatory effects.

Significant expression of Foxp3 in murine extrathymic CD4+CD8+ double positive T cells.

Forkhead box protein 3 (Foxp3) is a specific marker and the key factor in the development and function of regulatory T (Treg) cells. The present study investigates Foxp3 expression in murine head and neck lymph node (HNLN) and peripheral blood (PB) CD4+CD8+ double positive (DP) T cells and compares it with that in CD4+ or CD8+ single positive (SP) T cells. Here we provide evidence that murine extrathymic DP cells express Foxp3. We determined that the mean percentage of Foxp3-expressing cells within HNLN and PB DP cells was, respectively, 22.4 and 16.2. The obtained results clearly indicate that DP cells are very similar to CD4+ SP cells in respect of Foxp3 expression, and thus considerably deviate from CD8+ SP cells. It was found that Foxp3 expression in DP cells is positively correleted with CD25 expression. These results suggest that murine extrathymic Foxp3+ DP T cells may represent a unique regulatory T cell subset.

Distribution of CD4+CD8+ double positive T cells in a mouse model of allergic asthma.

The present study describes the distribution of CD4+CD8+ double-positive (DP) T cells in various immune compartments of mice with ovalbumin (OVA)-induced allergic asthma. It was found that the absolute number of DP T cells was considerably increased in the mediastinal lymph nodes and lungs of asthmatic mice as compared with that determined in the healthy subjects. On the contrary, the absolute counts of DP T cells was significantly decreased in the head and neck lymph nodes, and in peripheral blood of OVA-immunized mice. These results suggest that DP T cells may be involved in the pathogenesis of allergic asthma.

Pharmacology of topical prostaglandin F2 α analogs and their place in the treatment of glaucoma in small animals.

A distinguishing feature of the most common types of glaucoma is an increased intra-ocular pressure (IOP), which has a damaging effect on optic nerve axons, leading to the progressive loss of retinal ganglion cells. Therefore, IOP-lowering medications are the mainstay of glaucoma therapy. Topical prostaglandin F2 α analogs (PGAs) are a relatively new class of ocular hypotensive drugs, which have made a huge impact on the treatment of glaucoma in dogs. This study summarizes the current state of knowledge on the mechanism of action of these agents and their effect on IOP in dogs and cats. It also discusses potential harmful side effects of PGAs and presents contemporary opinions about their role and place in the medical management of glaucoma in small animals.

Prostaglandin E2 inhibits IL-10 production by bovine CD4+ T cells.

Although prostaglandin E2 (PGE2) is a pro-inflammatory mediator, it also produces some effect which is anti-inflammatory in character. It is suggested that one of the mechanisms responsible for the latter effect is the increased synthesis of IL-10. The aim of this study has been to determine the influence of PGE2 on IL-10 production by bovine CD4+ and CD8+ T cells and NK cells. With this aim, peripheral blood mononuclear cells collected from 12-month-old heifers (n = 10) were treated without or with PGE2 (10(-6) M). Flow cytometric analysis showed that PGE2 caused a reduction in the percentage of IL-10 producing CD4+ T cells (P < 0.001), while leaving the secretion of this cytokine by CD8+ T cells and NK cells unaffected. This seems to indicate that PGE2 in cattle does not produce an anti-inflammatory effect by increasing the synthesis of IL-10; contrary to this, it may aggravate an inflammatory response by inhibiting the secretion of this cytokine by CD4+ T cells.

Pharmacological characteristics of metamizole.

Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

Autonomic drugs in the treatment of canine and feline glaucoma--Part I: Medications that lower intraocular pressure by increasing the outflow of aqueous humour.

One characteristic of the most common types of glaucoma is increased intraocular pressure (IOP), which has a damaging effect on optic nerve axons, leading to progressive loss of retinal ganglion cells. Therefore, ocular hypotensive drugs are the mainstay of pharmacological therapy for glaucoma. This review article, which is the first part of a two-part series, is dedicated to autonomic drugs which lower IOP by increasing the outflow of aqueous humour. These agents are subdivided into two groups: (a) drugs that lower IOP by increasing the trabecular outflow and the uveoscleral outflow (i.e. nonselective adrenergic agonists), and (b) medications that lower IOP by opening of the drainage angle and by increasing the conventional outflow via the trabecular outflow (i.e. parasympathomimetics). This paper summarizes the current state of knowledge on the mechanism of action of these drugs and their effect on IOP in dogs and cats. Moreover, it discusses possible undesirable side effects of these medications and presents the current ideas about their role and position in the medical management of glaucoma in small animals.

Autonomic drugs in the treatment of canine and feline glaucoma--Part II: Medications that lower intraocular pressure by reducing aqueous humour production.

One characteristic of the most common types of glaucoma is increased intraocular pressure (IOP), which has a damaging effect on optic nerve axons, leading to progressive loss of retinal ganglion cells. Therefore, ocular hypotensive drugs are the mainstay of pharmacological therapy for glaucoma. This review article, which is the second part of a two-part series, is dedicated to autonomic drugs which lower IOP by decreasing the aqueous humour production. These agents are subdivided into two groups: ß-adrenergic antagonists and selective α2-adrenergic agonists. This paper summarizes the current state of knowledge on the mechanism of action of these drugs and their effect on IOP in dogs and cats. Moreover, it discusses their possible undesirable side effects of these medications and presents the current ideas about their role and position in the medical management of glaucoma in small animals.

Dexamethasone, but not meloxicam, suppresses proliferation of bovine CD25+ CD4+ and CD25- CD4+ T cells.

Recently, we found that dexamethasone caused a depletion of CD25- CD4+ T cells, but it increased the number of CD25highCD4+ and CD25lowCD4+ T cells. We also determined meloxicam-induced increase in the number of CD25highCD4+ T cells. In view of this, and taking into consideration the latest reports indicating that meloxicam shows an anti-proliferative effect on bovine peripheral blood mononuclear cells, it was considered purposeful to determine the effect of both drugs on proliferation of bovine CD25highCD4+, CD25lowCD4+ and CD25- CD4+ T cells. Flow cytometry analysis and 5-bromo-2'-deoxyuridine incorporation assay were applied to detect the cell proliferation. It was demonstrated that dexamethasone, but not meloxicam, significantly reduced cell proliferation within all three evaluated CD4+ T cell subpopulations. Thus, the depletion of CD25- CD4+ T cells by treatment with dexamethasone can partly be the effect of the anti-proliferative action of the drug, however, dexamethasone-induced increase in the number of CD25highCD4+ and CD25IowCD4+ T cells cannot be the result of enhanced proliferation of these cells.

Pharmacokinetics of orally administered simvastatin in turkeys.

The aim of the present study was to determine the pharmacokinetics of simvastatin (SIM) administered orally in 6-week-old turkeys at a single dose of 2 mg/kg b.w. The SIM concentrations in plasma were determined by validated HPLC-MS/MS method. Mean (+/- SD; n = 10) values of pharmacokinetic parameters evaluated were as follows: Cmax = 0.49 +/- 0.21 ng/ml, t(max) = 1.6 +/- 1.1 h, AUC(0-infinity) = 1.08 +/- 0.57 h x ng/ml, t1/2kel = 2.14 +/-1.3 h and MRT = 3.08 +/- 1.52 h. The results indicate that the SIM is absorbed from the gastrointestinal tract of turkeys; however, achieved plasma level is lower compared to those observed in mammals.

The presence of CD25 on bovine WC1+ gammadelta T cells is positively correlated with their production of IL-10 and TGF-beta, but not IFN-gamma.

WC1+ cells in cattle exhibit both regulatory and effector activities. However, it has not been elucidated whether they are so plastic that both activities co-exist in one cell or there are separate subpopulations of effector and regulatory cells. Since the production of IFN-gamma and IL-10 seems to be related to WC1+ cells' effector and regulatory function, respectively, the main aim of this study was to determine whether those cytokines are produced by separate subpopulations of WC1+, or are co-produced by the same cells. Due to increasingly frequent emphasised role of consumption of IL-2 in the mechanism of suppressor action of mouse CD25+CD4+ T regulatory cells, expression of the receptor's alpha chain for interleukin 2 (CD25) on WC1+ lymphocytes has been evaluated. An average of 5.21% of WC1+ cells obtained from PBMCs of 12-month-old heifers show constitutive expression of the CD25 molecule, with CD25(high)WC1+ and CD25(low)WC1+ cells accounting for 1.05% and 4.10% of WC1+ lymphocytes, respectively. For detection of intracellular cytokine production, PBMCs were stimulated with concanavalin A. Both IFN-gamma(-) and IL-10-producing cells within the CD25(-)WC1+ and CD25+WC1+ subpopulations were mainly separate subpopulations. The average percentage of IFN-gamma(+)IL-10(-), IFN-gamma(-)IL-10+ and IFN-gamma(+)IL-10+ cells among CD25(-)WC1+ lymphocytes was 4.03%, 2.67% and 0.51%, respectively. A positive correlation was observed between the presence of the CD25 molecule on WC1+ lymphocytes and production of IL-10 and TGF-beta, because the average percentage of IFN-gamma(-)IL-10+ and IFN-gamma(+)IL-10+ among CD25+WC1+ lymphocytes was 3 and 4.5 times higher as compared to the corresponding cells in the CD25(-)WC1+ subpopulation, whereas the percentage of IFN-gamma(+)IL-10(-) cells in both the subpopulations was not significantly different. The percentage of TGF-beta+ cells within the CD25+WC1+ subpopulation was 2.72 times as high as that of CD25(-)WC1+ lymphocytes. Therefore, with respect to the production of IFN-gamma, IL-10 and TGF-beta, CD25+WC1+ lymphocytes turn out to have a more suppressor profile than CD25(-)WC1+.

Participation of analogues of lysophosphatidic acid (LPA): oleoyl-sn-glycero-3-phosphate (L-alpha-LPA) and 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT) in uterine smooth muscle contractility of the pregnant pigs.

Recent studies show that a representative of phospholipids, namely lysophosphatidic acid (LPA) and its receptors (LPA1.3) play a significant role in the reproductive processes, i. a, in the modulation of the uterine contractility. The participation of LPA3 in the reproductive processes has been revealed in mice and has not been studied in gilts. Therefore, in the present study we investigated the role/action of LPA and its receptors LPA1, LPA2 and LPA3 on the contraction activity in the porcine uterus. The study was conducted on an experimental model in which the pig uterus consisted of the one whole uterine horn and a part of the second horn, both connected with the uterine corpus. Uterine strips consisting of the endometrium with the myometrium (ENDO/MYO) and myometrium (MYO) alone were collected on days 12-14 of the estrous cycle (control group; n = 5) or pregnancy (experimental group; n = 5). Two analogues of LPA at increasing doses were used: oleoyl-sn-glycero-3-phosphate (L-alpha-LPA, a selective agonist of LPA1 and LPA2 receptors; 10(-7) M; 10(-6) M and 10(-5) M) and 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT, a selective agonist of LPA3 receptor; 68 nM; 136 nM and 680 nM). L-alpha-LPA caused an increase in the contraction tension, amplitude and frequency of ENDO/MYO from the uterine horn with the developing embryos. This effect was not observed in MYO in both groups examined. In the ENDO/MYO strips of the uterine horn with developing embryos, OMPT significantly increased the contraction tension at the highest dose (680 nM) and amplitude at all doses examined, while frequency of contractions was decreased at doses of 136 nM and 680 nM. In the MYO strips of the uterine horn with embryos a significant increase in the contraction tension and amplitude after the highest dose of OMPT was observed. The results obtained imply the important role of receptors LPA1, LPA2 and LPA3 in the contraction activity of the porcine uterus during early pregnancy.

Evaluation of the influence of meloxicam and flunixin meglumine on the apoptosis of peripheral blood CD4+ and CD8+ T cells in calves.

The aim of the study was to determine whether treatment with recommended doses of meloxicam or flunixin had an effect on the apoptosis of peripheral blood T lymphocytes in calves. The study was carried out on 4-5 months old calves (n = 24, 8 per group). Experimental animals were injected subcutaneously with a single dose of 0.5 mg x kg(-1) of meloxicam or intravenously with 3 doses of 2.2 mg x kg(-1) day(-1) of flunixin. The non-treatment animals served as control. Blood samples were taken at day 0 and at days 1, 2, 3, 5, 7 and 14 after the first NSAIDs injection. Apoptosis was determined by flow cytometry using Annexin V-PE/7-AAD staining. The kinetic analysis of apoptosis in the total lymphocyte population, as well as in the CD4+ and CD8+ subsets did not reveal significant differences in the frequency of early apoptotic cells between control and experimental groups throughout the period studied. Although, 24 h after administration of the first dose of NSAIDs, late-stage apoptosis/necrosis was significantly increased in the total lymphocyte population (the meloxicam group), as well as in the CD4+ (the meloxicam group and the flunixin group) and CD8+ (the flunixin group) subsets of T cells. However, this disturbance was transient, relatively poorly expressed and, thus, unlikely to be of clinical significance. Our results indicate that the use of meloxicam or flunixin in accordance with the recommended dosage regimen in cattle do not have a clinically significant influence on apoptosis of peripheral blood T cells.

Influence of nonsteroidal anti-inflammatory drugs on progesterone production by cultured bovine luteal cells.

The objective of the present study was to determine the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) representing different chemical groups on progesterone (P4) production by cultured bovine steroidogenic luteal cells. The cells were enzymatically isolated from corpora lutea collected on days 8-12 of the estrous cycle. After 24 h preincubation they were incubated for 24 h with medium only (control) or stimulated with bovine luteinizing hormone - LH (100 ng/ml; positive control) or increasing concentrations (10(-8) to 10(-4) M) of acetylsalicylic acid, indomethacin, ibuprofen, naproxen, piroxicam, phenylbutazone, dipyrone or nimesulide. Concentartions of P4 in the culture media were determined by enzyme immunoassay. LH significantly increased P4 secretion, while acetylsalicylic acid and indomethacin did not affect the production of this hormone. A significant increase in P4 secretion was observed after administration of dipyrone at all concentrations, piroxicam at concentrations of 10(-8), 10(-7) and 10(-5) M, phenylbutazone and naproxen at concentrations of 10(-7) and 10(-6) M and ibuprofen at concentrations of 10(-5) and 10(-4) M. Nimesulide did not affect P4 production at concentrations of 10(-8) - 10(-5) M, while at a concentration of 10(-4) M it inhibited P4 secretion. The results obtained indicate that NSAIDs may change the production of P4 in bovine luteal cells, however, these changes are dependent on the substance used.

Effect of long-term treatment with therapeutic doses of enrofloxacin on chicken articular cartilage.

Quinolone-induced arthropathy has been observed after a single very large dose, or after several moderately large doses in juvenile animals of multiple species. The purpose of the present study was to determine whether long-term treatment with therapeutic doses of enrofloxacin has a detrimental effect on chicken articular cartilage. 21-day-old broiler chickens were treated orally with 10 mg/kg/day of enrofloxacin for 10, 20 and 35 days. 24 hours after the last dose, the animals were killed and the femoral head with condyles and tibial condyles were subjected to a gross and histopathological investigation. The necropsy did not reveal macroscopic visible pathological changes in the articular cartilage surface, as well as in soft tissues surrounding joints in any of the animals from this study. Also, light microscopy evaluation did not show significant histopathological changes in any of the specimens from either experimental and control animals. In conclusion, our results indicate that treatment with a therapeutic dose of enrofloxacin for a period exceeding the recommended duration of therapy does not cause arthropathy in growing chickens. Moreover, the results obtained seem to indicate that chondrotoxicity of quinolones does not have a cumulative nature.

Effect of increasing doses of enrofloxacin on chicken articular cartilage.

Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections in animals. Fluoroquinolones cause severe lesions in articular-epiphyseal cartilage complexes of growing mammals. The aim of the present study was to determine whether enrofloxacin has chondrotoxic, dose- and time-dependent effects on avian articular cartilage. 21-day-old male broiler chickens were treated orally with a single or five doses of 10, 50, 100, 300 and 600 mg/kg/day of enrofloxacin. 24 hours after the last dose the animals were killed and femoral head with condyles and tibial condyles were subject to a gross and histopathological investigation. The lesion scoring system was used to determine the progression of lesions. The mean score in birds treated with a single dose of 300 and 600 mg/kg of enrofloxacin was significantly increased when compared to the control group, while the administration of one dose of 10, 50 and 100 mg/kg of the drug did not cause substantial changes in the examined articular cartilages. The mean score was significantly greater in birds dosed for 5 days with 50, 100, 300 or 600 mg/kg/day of enrofloxacin when compared to the control group. Histologic changes included, among others, occurrence of chondrocytes with shrunken cytoplasm and pyknotic nuclei, spindle-shaped cells, clusters of chondrocytes and loss of proteoglycan. In conclusions, our results indicate that the use of enrofloxacin in growing chickens at recommended dosage is safe from the point of view of possibility of chondrotoxic effect. Only very high dosage of enrofloxacin, significantly exceeding the therapeutically applied doses, can induce toxic effects in articular cartilage and intensity of chondrotoxicity is dose- and time-dependent. Moreover, our findings suggest that quinolone-induced arthropathy is considerably less expressed in birds than in mammals.