lornoxicam and Disease-Models--Animal

Topics: Acute Disease; Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bite Force; Calcitonin Gene-Related Peptide; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Mandible; Molar, Third; Morphine; Movement; Neuropeptides; Pain Threshold; Pain, Postoperative; Piroxicam; Rats; Substance P; Tooth Extraction

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

This study proves the possibility of targeted use of the nonsteroidal anti-inflammatory drug lornoxicam to prevent the development of proliferative vitreoretinopathy (PVR). Triamcinolone acetonide (TA) was selected as a reference substance.. Wistar rats (N = 400) were used. PVR was modeled by intravitreal injection of dispase or concanavalin A. Lornoxicam or TA intravitreal administration was performed 20 min later. On the second and the third day, drugs were administrated systemic. Enucleation was performed on the first, third, seventh and 42nd or 56th day of the experiment.. Pro-inflammatory substances led to the development of sub- and epiretinal membranes. Lornoxicam decreased the incidence of membrane formation by 43 and 31% in dispase and concanavalin models, respectively. Membranes, formed during its use, were smaller and contained less fibrotic components. At the end of the experiment, the thickness of retinal and choroidal layers among the animals which had received the therapy was the same as the thickness of the retina and choroid of intact rats. Lornoxicam administration normalized the cyclooxygenases (COXs) expression in the retina and the choroid at the early stages of the experiment. TA application was less effective in both models.. COXs blocking during the development of PVR, overwhelming inflammation in the eye and reducing its consequences, is proved to be a much more effective and safe influence than the suppression of the entire cascade of arachidonic acid metabolism. Lornoxicam did not only improve the condition of the retina and the choroid but also significantly reduced the frequency of membrane formation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Concanavalin A; Disease Models, Animal; Intravitreal Injections; Piroxicam; Rats; Rats, Wistar; Retina; Triamcinolone Acetonide; Vitreoretinopathy, Proliferative; Vitreous Body

Transient receptor potential (TRP) cation channels are the largest group of sensory detector proteins expressed in the nerve terminals of many receptors including nociceptors, and are activated by temperature and chemicals that elicit hot or cold sensations. Antagonists of these channels are likely promising targets for new analgesic drugs at the peripheral and central levels. Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we investigated whether three widely used NSAIDs (diclofenac, ketorolac, and xefocam) affect thermal and mechanical hyperalgesia following the activation of TRPA1 and TRPV1 channels. We measured nociceptive thermal paw withdrawal latencies and mechanical thresholds bilaterally at various time points following intraplantar injection of the TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC) or the TRPV1 agonist capsaicin, or vehicle. When pretreated with vehicle, intraplantar injection of CA, AITC and capsaicin each resulted in significant decreases in thermal withdrawal latency and mechanical threshold in the ipsilateral hindpaw that did not return to baseline for more than 2h. To test effects of NSAIDS either diclofenac, ketorolac or xefocam was pre-injected in the same hindpaw 35min prior to CA, AITC or capsaicin. Pretreatment with each of the three NSAIDs produced strong antinociceptive and antihyperalgesic effects lasting approximately 60min. Thus, we show for the first time that local administration of NSAIDs reduces thermal and mechanical hyperalgesia following TRPA1 or TRPV1 activation.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Diclofenac; Disease Models, Animal; Hyperalgesia; Ketorolac; Male; Piroxicam; Rats; Rats, Wistar; Time Factors; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPV Cation Channels

Rheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX.. The LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund's complete adjuvant (FCA)-induced chronic arthritis.. The inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1β, prostaglandin E2, nuclear factor-κβ, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α.. LX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers; Carrageenan; Chronic Disease; Dinoprostone; Disease Models, Animal; Edema; Freund's Adjuvant; Interleukin-1beta; Male; Micelles; Nanoparticles; Piroxicam; Polymers; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

The objective of this work was to increase the solubility, in vitro skin permeability of lornoxicam from semisolid topical formulations and also to investigate the in vivo potential of nanoemulsion formulation. Optimized lornoxicam loaded nanoemulsion was prepared successfully by spontaneous self-emulsification method and the size of the stable formulations was found within the range of 102 to 200 nm. The stable nanoemulsion formulations characterized for viscosity, droplet size, transmission electron microscopy (TEM) and refractive index. In vitro permeation rate of nanoemulsion and conventional gel of lornoxicam (LX) were determined. Prmeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) were significantly increased in nanoemulsion NE8 and the nanogel NG8 as compared to conventional gel (LG). In vivo studies revealed a significant increase in anti-inflammatory effects as compared with conventional gel of LX. The anti-inflammatory effects of formulation NG8 showed a significant increase in percent inhibition value when compared with control, this difference was found to be highly significant (p<0.001). This work shows for the first time that lornoxicam can be formulated into nanoemulsions and may show promise in enhancing solubility and permeation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Disease Models, Animal; Edema; Emulsions; Freund's Adjuvant; Gels; Inflammation; Microscopy, Electron, Transmission; Nanomedicine; Nanoparticles; Particle Size; Permeability; Piroxicam; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility; Surface-Active Agents; Technology, Pharmaceutical; Viscosity

Clinical studies have revealed that patients with chronic pain are more likely to have anxiety and depression, which are often associated with cognitive dysfunction. However, whether neuropathic pain can induce cognition dysfunction remains uncertain. Antidepressants and nonsteroidal anti-inflammatory drugs can treat neuropathic pain, but whether they can prevent cognition dysfunction is unknown. The present study was designed to investigate the effects and possible mechanisms of neuropathic pain on learning and memory, and the effects of amitriptyline and lornoxicam on cognitive function.. Sixty male Sprague-Dawley rats were randomly subjected to L5 spinal nerve transection and sham operation, then given saline, amitriptyline and lornoxicam, respectively, during the postoperative days (7-28). Pain-related behaviours, depression-related behaviours, spatial learning and memory abilities, and expression of brain-derived neurotrophic factor were measured at different times after surgery.. L5 spinal nerve transection induced mechanical allodynia and depression, and decreased the function of learning and memory as well as the expression of brain-derived neurotrophic factor. Amitriptyline ameliorated mechanical allodynia and depression-related behaviour, improved the impaired cognition, and increased the expression of brain-derived neurotrophic factor, whereas lornoxicam only inhibited the mechanical allodynia.. We found that neuropathic pain may impair cognitive function via downregulation of the expression of brain-derived neurotrophic factor of the hippocampus, and amitriptyline rather than lornoxicam can ameliorate cognitive dysfunction via upregulation of brain-derived neurotrophic factor of the hippocampus.

Topics: Amitriptyline; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain-Derived Neurotrophic Factor; Cognition Disorders; Disease Models, Animal; Gene Expression Regulation; Hippocampus; Male; Maze Learning; Memory Disorders; Neuralgia; Piroxicam; Rats; Rats, Sprague-Dawley

We designed the current study to determine the protective effects of lornoxicam, a cyclooxygenase (COX) inhibitor, on recurrent herpetic stromal keratitis (HSK) and the nuclear factor-kappaB (NF-kappaB)-mediated mechanism in mice.. A corneal latent herpes simplex virus-1 (HSV-1) infected mouse model was established. Six weeks later, Ultraviolet B (UVB) irradiation induced the recurrence. Corneal swabs were obtained and cultured with indicator cells to determine shedding of the virus. Lornoxicam was administered intraperitoneally daily, beginning one day before irradiation and lasting for seven days. Saline-treated and mock-infected control groups were also studied at the same time. Development of corneal inflammation and opacity was scored. Immunohistochemical staining and an electrophoretic mobility shift assay were performed to evaluate the effect of lornoxicam on NF-kappaB activation in the corneal tissues. The levels of tumor necrosis factor-alpha (TNF-alpha) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA).. HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-kappaB and elevated production of TNF-alpha. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response.. Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Corneal Opacity; Corneal Stroma; Disease Models, Animal; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Herpesvirus 1, Human; Humans; Immunohistochemistry; Keratitis, Herpetic; Mice; Mice, Inbred ICR; NF-kappa B; Piroxicam; Tumor Necrosis Factor-alpha; Ultraviolet Rays; Virus Shedding

Activation of inflammation and enzyme cyclooxygenase with formation of proinflammatory prostaglandins is a key element of development of myocardial infarction in patients with acute coronary syndrome. Basing on literature data and own experience we suggested that single intravenous injection of 230 mg/kg of nonselective inhibitor of type 1 and 2 cyclooxygenase lornaxicam in the phase of initialization of inflammation 20 min after onset of ischemia would lead to reduction of myocardial infarction volume in rats in irreversible ischemia and ischemia with subsequent reperfusion. The conducted study allowed to reveal that administration of lornoxicam in recommended for human use dose lowered mortality of animals and increased number of capillaries per one cardiomyocyte in case of irreversible coronary artery occlusion. In ischemia-reperfusion as in irreversible myocardial ischemia lornoxicam reduced volume of necrosis and degree of thinning of left ventricular wall in the region of infarction, and lowered volume of connective tissue in periinfarction zone of the myocardium in remote period.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Ventricles; Male; Myocardial Infarction; Piroxicam; Rats; Reperfusion Injury; Treatment Outcome

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 1; Cyclooxygenase 2; Disease Models, Animal; Female; Gastric Mucosa; Ligation; Male; Piroxicam; Rats; Stomach Ulcer; Sulfonamides

To investigate the effects of intraperitoneally administered lornoxicam on adhesion formation, bursting pressure, tissue antioxidant levels, morbidity and mortality after ileocolic anastomosis in a rat bacterial peritonitis model.. Thirty-six rats were divided into three random groups. Bacterial peritonitis was induced by performing a cecal ligation and puncture, then the cecal was resected and ileocolic anastomosis was performed. Rats of groups 1, 2 and 3 were given 2 mL normal saline, 2 mL lornoxicam, and nothing, respectively. All groups were killed at day 14. Adhesions were scored, and the presence of intra-abdominal abscesses and fistulas were noted. Anastomotic healing was assessed by bursting pressure. Tissue antioxidant levels were tested from left abdominal walls.. One day after cecal ligation and puncture, microbiological examination showed polymicrobial bacterial peritonitis. The rats treated with lornoxicam had significantly lower adhesion scores than did the saline and nothing treated rats (P = 0.007). Bursting pressures of groups were unaffected by the treatment. Tissue antioxidant levels of groups were affected by the treatment. Morbidity and mortality were similar in all groups.. The present study demonstrated that a single intraperitoneal instillation of lornoxicam in buffer solution at the end of the surgery reduces adhesion formation in rats bacterial peritonitis model. It was also determined that lornoxicam had no negative effect on the healing of intestinal anastomosis, abscess and anastomotic leakage. Use of lornoxicam in peritonitis was effective in decreasing the oxidative stress of tissue during peritonitis.

Topics: Anastomosis, Surgical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Female; Oxidative Stress; Peritonitis; Piroxicam; Postoperative Complications; Pressure; Rats; Rats, Wistar; Tissue Adhesions; Wound Healing