potassium-permanganate and Disease-Models--Animal

Linear dermatitis (or dermatitis linearis, DL) is a skin blistering inflammatory lesion caused by exposure to the pederin toxin from rove beetles. Although it is prevalent in many countries of the Middle East region, this is not a notifiable disease. In recent years, a number of clinical symptoms outbreaks of DL has been reported from a few neighboring countries of Iran, but no report of experimental treatment among small laboratory rodents is known. This is a prerequisite to ascertain the nature of the best treatment strategy in cases of infestation with these beetles, as it occurs among local settlers during hot seasons in certain parts of the southern Iranian province of Fars. Live Paederus beetles were collected, identified to species level, sexed apart and partly processed to obtain their hemolymph toxin pederin in ethanol for dermal application on guinea pigs. Two Paederus species were found. Paederus ilsae (Bernhauer) (Coleoptera: Staphylinidae) was more abundant than P. iliensis (Coiffait). Recovery from DL due to live P. ilsae beetles was quicker and less complex than that of pederin in ethanol on guinea pigs. The application of potassium permanganate with calamine to heal DL was also more effective than fluocinolone treatment. This topical corticosteroid is thus considered less able to avert the cytotoxic action of pederin on the skin of guinea pigs than the antipruritic and cleansing agents. It seems likely that fluocinolone has certain effects which delays the recovery period for the treated skin.

Topics: Animals; Anti-Inflammatory Agents; Coleoptera; Dermatitis, Contact; Disease Models, Animal; Drug Combinations; Female; Ferric Compounds; Fluocinolone Acetonide; Guinea Pigs; Insect Bites and Stings; Iran; Male; Potassium Permanganate; Pyrans; Treatment Outcome; Zinc Oxide

Substance P (SP) is an important neuropeptide involved in neurogenic inflammation and most of its pathophysiological functions are mediated through binding to the neurokinin-1 receptor. SP exerts various proinflammatory actions on immune-cells, including macrophages. Several compounds such as cytokines have the capacity to activate and stimulate macrophages to produce arachidonic acid oxygenation and lipoxygenation products. Leukotriene B4 (LTB4) is one of the most important mediators of leukocyte activation in acute and chronic inflammatory reactions. LTB4 stimulates chemotaxis, lysosomal enzyme release, and cell aggregation. In this report, we studied the effect of SP on rat adherent granuloma macrophages (RAGMs). The chronic granuloma in rat was induced by dorsal injections of a potassium permanganate (KMnO4) saturated crystal solution (200 microl of a 1:40 dilution). After 7 days, all rats developed a subcutaneous granuloma in the injection site from which infiltrated macrophages were extracted, isolated, and cultured in vitro. We tested the hypothesis that SP stimulates the production of LTB4 in RAGMs and increases lipoxygenase expression. Here we show that the cell-free supernatant of RAGMs stimulated with SP (10 microM), resulted in statistically significant increases of LTB4 Preincubation of RAGMs with NDGA (nordihydroguaiaretic acid (10 microM), completely abolished the production of LTB(4) in the supernatants and lipoxygenase expression on RAGMs challenged with SP, or the cation ionophore A23187 (positive control). Similar effects were obtained when the cells were pretreated with dexamethasone (10 microM). Our results suggest that SP is able to stimulate the release of LTB4 and lipoxygenase expression in macrophages from chronic inflammatory granuloma and provide further evidence for a neuroinflammatory pathway.

Topics: Animals; Arachidonate 5-Lipoxygenase; Calcimycin; Dexamethasone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Granuloma; Ionophores; Leukotriene B4; Lipoxygenase Inhibitors; Macrophages; Male; Masoprocol; Microscopy, Electron, Transmission; Potassium Permanganate; Radioimmunoassay; Rats; Rats, Wistar; Substance P; Time Factors; Up-Regulation

RANTES (regulated on activation, normal T cell-expressed and secreted) is a CC chemokine appearing to be involved in the recruitment of leukocytes at inflammation sites. RANTES is produced by CD8(+) T cells, epithelial cells, fibroblasts, and platelets. It acts in vitro in leukocyte activation and human immunodeficiency virus suppression, but its role in vivo is still uncertain. In our study, we established the involvement of RANTES in an in vivo model of chronic inflammation induced by potassium permanganate, leading to calcified granulomas. In our rat model, RANTES expression (mRNA and protein) was significantly upregulated in granulomatous tissue; RANTES expression was further increased upon i.p. injection of lipopolysaccharide (LPS), while it was kept at basal levels by dexamethasone (Dex) given 18 hours before sacrifice. LPS and Dex increased and decreased, respectively, the recruitment of mononuclear cells in granulomatous tissue compared with control granulomas from phosphate-buffered saline (PBS)-treated animals. In granuloma tissue, levels of RANTES were higher in LPS-treated rats and lower in the Dex group compared to controls. RANTES was also found in the conditioned medium of granuloma tissue from treated (LPS or Dex) and untreated (PBS) rats. When LPS was added in vitro for 18 hours, RANTES was further increased, except in the Dex group (P > 0.05). On serum analysis, RANTES levels were higher in the LPS group and lower in the Dex group compared to controls. This study shows for the first time that RANTES is produced in vivo in chronic, experimental inflammatory states, an effect increased by LPS and inhibited by Dex.

Topics: Animals; Anti-Inflammatory Agents; Chemokine CCL5; Chronic Disease; Dexamethasone; Disease Models, Animal; Gene Expression Regulation; Granuloma; Inflammation; Lipopolysaccharides; Potassium Permanganate; Rats; Rats, Wistar; RNA, Messenger

Myo-inositol hexaphosphate (InsP6) is an abundant component of plant seeds. It is also found in significant levels in blood and mammalian tissues, but they are totally dependent on their dietary intake. In the present paper, we describe studies on the effect of InsP6 on a model of dystrophic calcification, which was chemically induced by subcutaneous injection of a 0.1% KMnO4 solution. Male Wistar rats were randomly divided into four groups for treatment over 31 days. A: animals consuming a purified diet in which InsP6 was absent but to which 1% of InsP6 (as sodium salt) was added. In this group, the InsP6 plasma levels (0.393 +/- 0.013 microM) were similar to those observed in rats consuming a standard diet. B: animals consuming only the purified diet in which InsP6 was absent. In this case the InsP6 plasma levels decreased (0.026 +/- 0.006 microM); C: animals consuming the same purified diet as group B but received daily subcutaneous injections of 50 microg kg(-1) etidronate during the last 14 days. In this case the InsP6 plasma levels were also very low (0.025 +/- 0.007 microM); D: animals consuming the same diet as group B but a 6% of carob germ (InsP6 rich product) was added. The InsP6 plasma levels (0.363 +/- 0.035 microM) were also similar to those observed in rats consuming a standard diet. After 21 days plaque formation was induced. Calcification plaques were allowed to proceed for 10 days, after which the plaque material present was excised, dried and weighed. It was found that the presence of myo-inositol hexaphosphate (phytate) in plasma at normal concentrations (0.3-0.4 microM) clearly inhibited the development of dystrophic calcifications in soft tissues. These results demonstrates that myo-inositol hexaphosphate acts as an inhibitor of calcium salt crystallization.

Topics: Administration, Oral; Animals; Calcinosis; Diet; Disease Models, Animal; Etidronic Acid; Injections, Subcutaneous; Male; Phytic Acid; Pilot Projects; Potassium Permanganate; Rats; Rats, Wistar

Hydroxyapatite crystal deposition is thought to play a role in the inflammatory episodes of osteoarthritis. A plaque of hydroxyapatite crystals was produced by local subcutaneous injection of a potassium permanganate solution. Transmission electron microscopy with X-ray energy spectroscopy was used to identify the crystal deposits as hydroxyapatite. The effects of dexamethasone, indomethacin, ethane 1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diposphonate (Cl2MDP) on the development of the apatite plaque was studied. EHDP strongly inhibited the apatite deposition. Cl2MDP slowed the natural resorption of the apatite plaque. Dexamethasone and indomethacin failed to affect the crystal deposition process. The results suggest that EHDP could inhibit crystal deposition in the osteoarthritic joint and that Cl2MDP might have a role in slowing apatite crystal shedding from osteoarthritic cartilage and so reduce the synovitis seen in Osteoarthritis.

Topics: Animals; Calcinosis; Clodronic Acid; Dexamethasone; Disease Models, Animal; Etidronic Acid; Hydroxyapatites; Indomethacin; Male; Osteoarthritis; Potassium Permanganate; Rats; Spectrophotometry, Infrared; Time Factors