Anacardic acids from cashew nuts ameliorate lung damage induced by exposure to diesel exhaust particles in mice.

Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50 µ g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100 µ L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.

Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

AIM OF THE STUDY: Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. MATERIALS AND METHODS: We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. RESULTS: Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. CONCLUSIONS: The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo.

Efeitos dos ácidos anacárdicos no sistema respiratório de camundongos submetidos à instilação intranasal de partículas resultantes da combustão de diesel / Effects of the anacardic acids in the respiratory system of mice after intranasal instillation of diesel exhaust particles

Os ácidos anacárdicos (AAs) provenientes do líquido da casca da castanha de caju têm propriedades antioxidantes e anti-inflamatórias. Seus efeitos são bem estabelecidos em vários sistemas in vitro, no entanto não há publicações a respeito de suas ações no tecido pulmonar. No presente estudo, foram analisados os efeitos da suplementação dos AAs em modelo de inflamação subaguda induzida pelas partículas resultantes da combustão do diesel (DEP) em camundongos. Camundongos BALB/c machos receberam por 20 dias consecutivos instilação intranasal de 50 g DEP diluídos em 10 L de salina. Como pré-tratamento, 10 dias antes do ínicio da instilação intranasal com DEP, os animais foram tratados por via oral com 50, 150 ou 250 mg/kg de AAs diluídos em 100 L de óleo da castanha de caju ou apenas 100 L de óleo da castanha de caju (veículo). Foram analisados: a densidade de células inflamatórias, as células imunomarcadas para TNF-, NF-B e KC e a área imunomarcada para 8-isoprostano no parênquima pulmonar. Além disso, foi mensurado o perfil celular e de citocinas no LBA e a área imunomarcada por VCAM e KC nos vasos peribronquiolares. As atividades das enzimas antioxidantes GR, GPx, GST e CAT foram analisadas no tecido pulmonar e no sangue periférico. O tratamento com os AAs foram capazes de agir como substâncias protetoras no parênquima pulmonar. A dose de 50 mg/kg demonstrou efeitos mais proeminentes na redução dos marcadores de inflamação pulmonar, no entanto as três doses foram capazes de atuarem como substâncias antioxidantes aumentando a atividade das enzimas antioxidantes e reduzindo a expressão de VCAM nos vasos pulmonares na presença da sobrecarga oxidativa induzida pelas DEP. Portanto, os AAs demonstraram ter potencial preventivo contra os efeitos das DEP no sistema respiratório, atuando como substâncias naturais com propriedades anti-inflamatórias e antioxidantes.

Anacardic acids (AAs) from cashew nut shell liquid have important antioxidant properties. However despite their well established effects in several systems in vitro, there were no reports about their effects in lung tissue. In this present study, we examined the effects of AAs supplementation in a model of low diesel exhaust particles (DEP) induced lung inflammation in mice. Male BALB/c mice received intranasal instillation of 50 g DEP diluted in 10 L of saline solution during 20 days. Ten days before instillation, animals were oral treated by the following 30 days with 50, 150 or 250 mg/Kg AAs diluted in 100 L of cashew nut oil (CNO) or vehicle (100 L of CNO). In order to evaluate anti-inflammatory and antioxidant effects, we analyzed the influx of inflammatory cells, TNF-, NF-B and KC positive cells; and the expression of 8-isoprostane in alveolar parenchyma. In addition, we measured the cellular profile and cytokines level in BALF and the VCAM and KC expressions in peribronchiolar pulmonary vessels.The activities of antioxidant enzymes GR, GPx, GST and CAT were analyzed by spectrophotometric method to assessing oxidative status in the lung tissue and in the peripheral blood. Treatment with AAs was able to act as a protective substance in lung tissue. The dose of 50 mg/kg showed more prominent effects in decreasing the inflammatory markers caused by DEP, however all the three doses are able to preserve antioxidant enzymes activities in the presence of oxidative charge and decreased the expression of VCAM in vessels. Furthermore, we demonstrated that AAs, which are natural substance, have potential effects against air pollution-related effects in respiratory system, acting as anti-inflammatory and antioxidant properties.