Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPARα)-deficient mice

Abstract Background Peroxisome proliferator activated receptor alpha (PPARα), a regulator of enzymes involved in β oxidation, has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPARα plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA). Methods Wild type (wt) or PPARα-deficient (PPARα−/−) mice were treated with ConA (15 mg/kg) by intravenous injection 0, 10 or 24 h prior to sacrifice and serum and tissue collection for analysis of tissue injury, cytokine response, T cell activation and characterization. Results Ten and 24 h following ConA administration, wt mice had significant liver injury as demonstrated by serum transaminase levels, inflammatory cell infiltrate, hepatocyte apoptosis, and expression of several cytokines including interleukin 4 (IL4) and interferon gamma (IFNγ). In contrast, PPARα−/− mice were protected from ConA-induced liver injury with significant reductions in serum enzyme release, greatly reduced inflammatory cell infiltrate, hepatocellular apoptosis, and IFNγ expression, despite having similar levels of hepatic T cell activation and IL4 expression. This resistance to liver injury was correlated with reduced numbers of hepatic natural killer T (NKT) cells and their in vivo responsiveness to alpha-galactosylceramide. Interestingly, adoptive transfer of either wt or PPARα−/− splenocytes reconstituted ConA liver injury and cytokine production in lymphocyte-deficient, severe combined immunodeficient mice implicating PPARα within the liver, possibly through support of IL15 expression and/or suppression of IL12 production and not the lymphocyte as the key regulator of T cell activity and ConA-induced liver injury. Conclusion Taken together, these data suggest that PPARα within the liver plays an important role in ConA-mediated liver injury through regulation of NKT cell recruitment and/or survival.

Efecto letal agudo de los insecticidas en formulación comercial Imidacloprid, Spinosad y Thiocyclam hidrogenoxalato en obreras de Bombus atratus (Hymenoptera: Apidae) / Acute lethal effect of the commercial formulation of the insecticides Imidacloprid, Spinosad y Thiocyclam hidrogenoxalate in Bombus atratus (Hymenoptera: Apidae) workers

Resumen:Los efectos de los insecticidas sobre las abejas han cobrado gran atención a nivel mundial, sin embargo, son pocos los estudios sobre el efecto de estos agroquímicos en abejas Neotropicales. Bombus atratus es una especie neotropical, distribuida ampliamente en los Andes y es considerado un polinizador importante de ecosistemas y agroecosistemas altoandinos. Sin embargo, al igual que muchas especies silvestres, se desconoce el efecto de los insecticidas en B. atratus. Teniendo en cuenta lo anterior, el presente trabajo determinó la dosis letal media aguda (DL50) por exposición tópica y oral de las formulaciones comerciales de los insecticidas con los ingredientes activos Imidacloprid, Spinosad y Thiocyclam hidrogenoxalato, ampliamente utilizados para el control de plagas de cultivos importantes en Colombia. Las pruebas DL50 se realizaron a partir de modificaciones de los lineamientos establecidos por la EPPO y OEDE para estas pruebas en Apis mellifera. Se evaluaron 5 dosis para cada insecticida y exposición. Se evaluaron 25 obreras de tamaño medio en cada dosis por duplicado. La mortalidad se registró a las 24, 48 y 72 horas después del experimento. Los datos fueron analizados con el modelo de regresión Probit. Para el Imidacloprid la DL50 tópica y oral fue de 0.048 µg/abeja y 0.010 µg/abeja respectivamente. Para el Thiocyclam hidrogenoxalato la DL50 tópica y oral fue de 0.244 µg/abeja y de 0.056 µg/abeja respectivamente. Para el Spinosad, la DL50 por exposición oral correspondió a 0.28 µg/abeja. No fue posible establecer la DL50 por exposición tópica. A partir del cálculo del Cociente de Riesgo (HQ) e Índice de Toxicidad Relativa, los tres ingredientes activos son altamente tóxicos. Se analiza y discute el riesgo debido al uso de los productos evaluados a partir de la naturaleza química de los insecticidas.

Abstract:The effect of insecticides on bees has gained great attention, however, there are few studies that explore this issue on Neotropical bees. Bombus atratus is a neotropical species broadly distributed in Colombia and is considered an important pollinator of both Andean ecosystems and agroecosystems. However, as for many wild bees species, the effect of insecticides on B. atratus is unknow. In this study we determined the acute median lethal dose (LD50) of commercial formulations of insecticides Imidacloprid, Spinosad and Thiocyclam hydrogen oxalate, widely used in Colombia to control several pests of important crops. The LD50 was carried out by oral and contact routes, following and modifying the EPPO and OECD guidelines to perform LD50 on A. mellifera. We evaluated five doses for each route and insecticide, in a total of 25 medium-size workers for each dose by duplicate. Mortality was registered at 24, 48 and 72 hours after the experiment; and data were analyzed with the Probit regression model. For Imidacloprid, contacts and oral LD50 were 0.048 µg/bee and 0.010 µg/bee, respectively. For Thiocyclam hydrogen oxalate, topical and oral LD50 were 0.244 µg/bee and 0.056 µg/bee, respectively. For Spinosad, the oral LD50 corresponded to 0.28 µg/bee; it was not possible to establish the LD50 for the contact route. The Hazard Quotient (HQ) and Index of Relative Toxicity indicated that all three active ingredients are highly toxic. We discussed the risk of the insecticides use on B. atratus, considering their chemical nature. Rev. Biol. Trop. 64 (4): 1737-1745. Epub 2016 December 01.

Comparative hematological and histopathological toxicity of two potential bio-insecticides against albino rats

Ivermectin [1.8% E.C] and spinosad [24% SC] are bioinsecticides produced by fermentation of some bacteria species. These compounds were selected to evaluate their haematological and histopathological toxicities against albino rats. The tested compounds were orally administrated to rats at 1/10 LD[50] every three days for one month period. Hemoglobin value [HB], red blood cells [RBC], white blood cells [WBC] and platelets [PLT] counts, gamma glutamyl transferase [gammaGT] were determined in addition to histopathological examinations for liver, spleen and kidney. In general, both compounds induced significant changes in HB value, RBC, WBC, PLT counts, and gammaGT activity after 30 days from treatment. Ivermectin caused significant rise in creatinine level at the same period. Histopathological examination showed disturbance in hepatic lobules, inflammatory infiltration, and pyknotic and karyolitic nuclei in hepatocytes. Kidney exhibited lobulated glomeruli and degenerative tubules, but interstitial hemorrhagic areas were noticed in spleen. Although the tested compounds are biopesticides, obtained data revealed that both compounds caused undesirable effects on experimental animals, so we conclude not to use them on plants during fruit stage or on fresh vegetables

Antimalarial activity of concanamycin A alone and in combination with pyronaridine.

Concanamycin A, a macrolide antibiotic inhibitor of vacuolar H+-ATPase derived from Streptomyces sp, inhibited Plasmodium falciparum K1 growth in culture with an IC500 value of 0.2 nM. It exhibited an additive effect when tested together with the antimalarial pyronaridine.