Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses

In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders

Phytic Acid Decreases Oxidative Stress and Intestinal Lesions Induced by Fumonisin B1 and Deoxynivalenol in Intestinal Explants of Pigs

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B1 (FB1) and/or deoxynivalenol (DON). The jejunal explants were exposed to the following treatments: vehicle, IP6 5 mM, DON 10 µM, FB1 70 µM, DON 10 µM + FB1 70 µM, DON 10 µM + IP6 5 mM, FB1 70 µM + IP6 5 mM, and DON 10 µM + FB1 70 µM + IP6 5 mM. The decrease in villus height and goblet cell density was more evident in DON and DON + FB1 treatments. In addition, a significant increase in cell apoptosis and cell proliferation and a decrease in E-cadherin expression were observed in the same groups. DON and FB1 exposure increased cyclooxygenase-2 expression and decreased the cellular antioxidant capacity. An increase in lipid peroxidation was observed in DON- and FB1-treated groups. IP6 showed beneficial effects, such as a reduction in intestinal morphological changes, cell apoptosis, cell proliferation, and cyclooxygenase-2 expression, and an increase in E-cadherin expression when compared with DON, FB1 alone, or DON and FB1 in association. IP6 inhibited oxidative stress and increased the antioxidant capacity in the explants exposed to mycotoxins

Pimaradienoic Acid Inhibits Carrageenan-Induced Inflammatory Leukocyte Recruitment and Edema in Mice: Inhibition of Oxidative Stress, Nitric Oxide and Cytokine Production.

Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation

5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality

Submitted by Luciane Willcox ([email protected]) on 2016-09-02T15:32:06Z No. of bitstreams: 1 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf: 2492175 bytes, checksum: 659775e09693604e324165fb1c495a21 (MD5)Approved for entry into archive by Luciane Willcox ([email protected]) on 2016-09-02T15:50:44Z (GMT) No. of bitstreams: 1 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf: 2492175 bytes, checksum: 659775e09693604e324165fb1c495a21 (MD5)Made available in DSpace on 2016-09-02T15:50:44Z (GMT). No. of bitstreams: 1 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf: 2492175 bytes, checksum: 659775e09693604e324165fb1c495a21 (MD5) Previous issue date: 2013-10-31This work was supported by grants from SETI/Fundação Araucária, Paraná State Government, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage

Pimaradienoic acid (PA) inhibits carrageenan-induced nitric oxide (NO) production.

<p>Mice were treated per oral (p.o.) with PA (10 mg/kg) or vehicle (DMSO 2% diluted in saline) 30 minutes before the intraperitoneal (i.p.) injection of carrageenan (300 μg/paw). Nitrite production in peritoneal exudates was determined 3 hours after carrageenan injection. Results are means ± SEM of six mice per group per experiment, and are representative of two separate experiments. [*p<0.05 compared with the saline group, and #p< 0.05 compared to the vehicle group (One-way ANOVA followed by Tukey’s test)].</p

Pimaradienoic acid (PA) inhibits carrageenan-induced oxidative stress.

<p>Mice were treated per oral (p.o.) with PA (10 mg/kg) or vehicle (DMSO 2% diluted in saline) 30 minutes before the intraplantar (i.pl.) injection of carrageenan (300 μg/paw). Paw skin (A) GSH levels, (B) ABTS⁺ scavenging activity, (C) the ability to reduce iron (FRAP), and (D) superoxide anion production were determined 3 hours after carrageenan injection. Results are means ± SEM of six mice per group per experiment, and are representative of two separate experiments. [*p<0.05 compared to the saline group; #p<0.05 compared to inflammatory stimulus group. (One-way ANOVA followed by Tukey’s test)].</p

Pimaradienoic acid (PA) structure.

<p>Chemical structure of PA[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149656#pone.0149656.ref029" target="_blank">29</a>].</p

Pimaradienoic acid (PA) inhibits carrageenan-induced total leukocyte and neutrophil recruitment in the peritoneal cavity.

<p>Mice were treated per oral (p.o.) with PA (0.1–10 mg/kg) or vehicle (DMSO 2% diluted in saline) 30 minutes before carrageenan (500 μg/ cavity) intraperitoneal (i.p.) injection. The (A) total number of leukocytes, (B) neutrophils and (C) mononuclear cells was evaluated 6 hours after carrageenan injection. Results are means ± SEM of six mice per group per experiment and are representative of two separate experiments. [*p < 0.05 compared to the saline group; #p < 0.05 compared to the vehicle group (One-way ANOVA followed by Tukey’s test)].</p

Pimaradienoic acid (PA) inhibits carrageenan-induced paw edema and myeloperoxidase (MPO) activity.

<p>Mice were treated per oral (p.o.) with PA (10 mg/kg) or vehicle (DMSO 2% diluted in saline) 30 minutes before the intraplantar (i.pl.) injection of carrageenan (300 μg/paw). The evaluation of (A) paw edema was at 1–5 hours and (B) MPO activity at 5 hours after carrageenan injection. Results are means ± SEM of six mice per group per experiment, and are representative of two separate experiments. [*p< 0.05 compared with the saline group, #p <0.05 compared to the vehicle group (One-way ANOVA followed by Tukey’s test)].</p