ABSTRACT
Photodynamic therapy (PDT) has proven to be an effective alternative for the treatment of cutaneous leishmaniasis. Skin lesions consist of ulcers with well-defined raised edges, and granular floor. Th1 immune response is the protective profile in patients infected with Leishmania. In this study, the photodynamic therapy with 5-aminolevulinic acid, the parasitic load, and the modulation of the immune response was evaluated in mice infected with Leishmania braziliensis. Balb/c mice were infected with L. braziliensis and subsequently treated with three sections of PDT. The parasite load and mRNA expression of cytokines (IFN-γ, IL-4, IL-17, IL-22, IL-27, IL-10) and transcription factors (GATA-3, Foxp3 and T-bet) were analysed by quantitative PCR. The parasite load in the treated group was significantly lower than in the untreated group (P<.0001); in PDT treated animals, we observed an increase in IFN-γ and T-bet mRNA (P=.012 and P=.0071). There was a significant reduction in mRNA expression of IL-22 associated with an increased expression of IL-27 mRNA in the animals treated with light only (P=.0001). 5-ALA associated with photodynamic therapy promotes a reduction in parasite load and an increased expression of IFN-γ and T-bet mRNA.
Subject(s)
Aminolevulinic Acid/therapeutic use , Leishmania braziliensis/parasitology , Leishmaniasis, Cutaneous/therapy , Photochemotherapy , Photosensitizing Agents/therapeutic use , Animals , Cytokines/biosynthesis , Interferon-gamma , Leishmania braziliensis/immunology , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Male , Mice , Mice, Inbred BALB C , Parasite Load , RNA, Messenger , Transcription Factors/biosynthesisABSTRACT
This study assessed the effect of the agonist 15d-PGJ(2) administered into the rat temporomandibular joint (TMJ) on nociceptive behavioral and the anti-inflammatory potential of this prostaglandin on TMJ. It was observed that 15-deoxy-(Delta12,14)-prostaglandin J(2) (15d-PGJ(2)) significantly reduced formalin-induced nociceptive behavior in a dose dependent manner, however injection of 15d-PGJ(2) into the contralateral TMJ failed to reduce such effects. This antinociceptive effect is dependent on peroxisome proliferator-activated receptors-gamma (PPAR-gamma) since pre-treatment with GW9662 (PPAR-gamma receptor antagonist) blocked the antinociceptive effect of 15d-PGJ(2) in the TMJ. In addition, the antinociceptive effect of 15d-PGJ(2) was also blocked by naloxone suggesting the involvement of peripheral opioids in the process. Confirming this hypothesis pre-treatment with kappa, delta, but not mu receptor antagonists significantly reduced the antinociceptive effect of 15d-PGJ(2) in the TMJ. Similarly to opioid agonists, the 15d-PGJ(2) antinociceptive action depends on the nitric oxide (NO)/guanilate cyclase (cGMP)/ATP-sensitive potassium channel blocker(K(+)(ATP)) channel pathway since it was prevented by the pre-treatment with the inhibitors of nitric oxide synthase (NOS; aminoguanidine), cGMP (ODQ), or the K(+)(ATP) (glibenclamide). In addition, 15d-PGJ(2) (100 ng/TMJ) inhibits 5-HT-induced TMJ hypernociception. Besides, TMJ treated with 15d-PGJ(2) showed lower vascular permeability, assessed by Evan's Blue extravasation, and also lower neutrophil migration induced by carrageenan administration. Taken together, these results demonstrate that 15d-PGJ(2) has a potential peripheral antinociceptive and anti-inflammatory effect in the TMJ via PPAR-gamma activation. The results also suggest that 15d-PGJ(2) induced-peripheral antinociceptive response in the TMJ is mediated by kappa/delta opioid receptors by the activation of the intracellular l-arginine/NO/cGMP/K(+)(ATP) channel pathway. The pharmacological properties of the peripheral administration of 15d-PGJ(2) highlight the potential use of this PPAR-gamma agonist on TMJ inflammatory pain conditions.
Subject(s)
Analgesics/pharmacology , Pain/drug therapy , Prostaglandin D2/analogs & derivatives , Receptors, Opioid, delta/metabolism , Receptors, Opioid, kappa/metabolism , Temporomandibular Joint/drug effects , Analgesics/administration & dosage , Animals , Cyclic GMP/antagonists & inhibitors , Cyclic GMP/metabolism , Dose-Response Relationship, Drug , Formaldehyde , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , KATP Channels/antagonists & inhibitors , KATP Channels/metabolism , Male , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , PPAR gamma/antagonists & inhibitors , PPAR gamma/metabolism , Pain/chemically induced , Pain/metabolism , Prostaglandin D2/administration & dosage , Prostaglandin D2/pharmacology , Rats , Rats, Wistar , Receptors, Opioid, delta/antagonists & inhibitors , Receptors, Opioid, kappa/antagonists & inhibitors , Receptors, Opioid, mu/antagonists & inhibitors , Receptors, Opioid, mu/metabolism , Serotonin/metabolism , Signal Transduction , Temporomandibular Joint/metabolismABSTRACT
OBJECTIVE: Recently, an orally transmitted outbreak of Chagas disease was reported in Santa Catarina, Brazil, after ingestion of sugar cane juice (garapa). This disease is caused by Trypanosoma cruzi, a parasite that stimulates the development of chronic inflammatory response, characterized by fibrous connective tissue neoformation (fibrosis). As the density of tissue mast cells (MC) may be an index of fibroblast proliferation and development of local fibrosis, the purpose of this autopsy study was to quantify the fibrosis rate and the number of MC in the tongues of chronic chagasic (CC) patients, compared with a non-chagasic (NC) control group. METHODOLOGY: Twenty-four evaluations, with a quantitative assessment of fibrosis percentage and MC density were performed. RESULTS: The percentage of fibrosis in the tongue was higher among CC than in the control group. In the CC group, a positive and significant correlation was found when the fibrosis rate was compared with the MC density. CONCLUSIONS: These morphometric findings suggest that tongue biopsy may be useful to study specific changes associated with Chagas disease. They also suggest that the systematic analysis of oral cavity, including tongue histopathology changes, could be useful in forensic pathology of the orally acquired chronic Chagas disease.
