Aerobic exercise combined with huwentoxin-I upregulates phase-Ⅱ detoxification enzymes to alleviate obstructive jaundice-induced central nervous system injury in mice / 南方医科大学学报

OBJECTIVE@#To explore the effects of aerobic exercise combined with huwentoxin-I (HWTX-I)-mediated Keap1-Nrf2-ARE pathway on phase II detoxification enzymes HO-1 and NQO1 and their protective effects against obstructive jaundice (OJ)-induced central nervous system injury in mice.@*METHODS@#50 male KM mice were randomly divided into blank group (GO), model group (M), aerobic exercise group (T), HWTX-I group (H), and aerobic exercise combined with HWTX-I group (TH). Mouse models of OJ were established with surgical suture for 72 h in the mice in all the groups except for the blank control group. The mice received interventions by aerobic exercise and tail vein injection of HWTX-I (0.05 μg/g) and were assessed by behavioral observation, Clark's neurological function scores, enzyme-linked immunosorbent assay (ELISA), brain tissue Nissl staining, hippocampal tissue Western blotting, and liver tissue mRNA expression profiling and sequencing.@*RESULTS@#The mice in group M had obvious jaundice symptoms after the operation with significantly increased Clark's neurological score ( < 0.01). Compared with those in group M, the mice in group T, group H, and group TH showed significantly decreased serum levels of ALT, AST, TBIL, and TBA ( < 0.01) with increased contents of 5-HT and BDNF and decreased contents of S100B and NSE in the hippocampus ( < 0.01). Synergistic effects between aerobic exercise and HWTX-I were noted on the above parameters except for the liver function indicators. Interventions with aerobic exercise and HWTX-I, alone or in combination, obviously lessened pathologies in the brain tissue induced by OJ, and the combined treatment produced the strongest effect. The treatment also increased the expression levels of Nrf2, HO-1, and NQO1 mRNA and protein in brain tissues ( < 0.01 or 0.05) with a synergistic effect between aerobic exercise and HWTX-I. Illumina high-throughput sequencing showed that the differentially expressed factors participated mainly in such neural regulatory pathways as neuroactive ligand-receptor interaction, GABAergic synapses, dopaminergic synapses, synaptic vesicle circulation, and axon guidance, involving tissue cell neuronal signal transduction, apoptosis inhibition, immune response, and toxicity. Aerobic exercise and HWTX-I synergistically increased the accumulation of the signal pathways related with neuron damage repair and proliferation.@*CONCLUSIONS@#Aerobic exercise combined with HWTX-I can up-regulate the expression of phase Ⅱ detoxification enzymes HO-1 and NQO1 through the Keap1-Nrf2-ARE pathway to protect the central nervous system against OJ-induced damage in mice.

Mecanismos de resistencia a la permetrina en dos poblaciones de Aedes aegypti del occidente de Venezuela / Mechanisms of Permethrin resistance in two populations of Aedes aegypti in westernVenezuela

Se determinó la resistencia a la permetrina en Aedes aegypti de los estados Trujillo y Zulia mediante bioensayos de botella. Los insectos derribados durante la hora de exposición fueron registrados y usados para calcular la Concentración Knock-down cincuenta (CK50) y los muertos a las 24 horas para la Concentración Letal cincuenta(CL50). La resistencia al derribo y post-recuperación fueron determinadas calculando del Factor de Resistencia FRCK50 y FRCL50, comparando los valores de CK50 y CL50de las poblaciones de Ae. aegypti de campo con los de la cepa susceptible New Orleans obtenidos mediante análisis de regresión log-probit. Mecanismos metabólicos y no metabólicos asociados a la resistencia, fueron evaluados midiendo los niveles de las enzimas alfa-esterasas, beta-esterasas, oxidasas de función múltiple y glutatión-S-transferasas mediante la técnica de microplacas y determinando la frecuencia alélica I1016 por PCR alelo específico. Ambas poblaciones mostraron baja resistencia al derribo (FRCK50 < 5) y moderada resistencia post-recuperación (FRCL50 entre 5 y 10). Sobre-expresión de alfa-esterasas fue observada en la población Loma Linda la cual se correlacionó significativamente con la CL50. En la población Pampanito la frecuencia del alelo I1016 fue de 0,1 y en Loma Linda de 0,17, observándose homocigotos mutantes solo en esta última población. Se evidencia la presencia de mecanismos metabólicos y no metabólicos asociados a la resistencia al derribo y post-recuperación a la permetrina en las poblaciones bajo estudio, lo cual debe ser considerado antes de la aplicación de piretroides para el control de Ae. aegypti en la zona de estudio.

Permethrin resistance was determined in Aedes aegypti populations from Trujillo and Zulia states using the bottle bioassay method. Insect knock-down rates during 1h of exposure were recorded and used to calculate the 50% knock-down concentration (KC50) and the mortality after 24 h (LC50). Knock-down and post-recovery resistance were determined by calculating the resistance factors, FRKC50 and FRLC50 . This was done by comparing the KC50 and LC50 values (obtained by regression analysis log-probit) of the field populations with a susceptible New Orleans strain. Metabolic and non-metabolic mechanisms associated with resistance were assessed by measuring the levels of the following enzymes: alpha-esterases, beta-esterases, mixed function oxidases (MFOs) and glutathione-S-transferases (GSTs) using the microplate technique. We also determined the alellic frequency of I1016 by allele specific PCR. Both populations showed a low knock-down resistance (FRKC50 < 5) and moderate post-recovery resistance (FRLC50 between 5 and 10). Overexpression of alpha-esterases was observed in the Loma Linda population and was significantly correlated with the LC50 . The frequency of the I1016 allele was 0.1 for the Pampanito population and 0.17 for the Loma Linda population, and in the latter we also observed homozygous mutants. The existence of metabolic and non-metabolic mechanisms associated with knockdown resistance and post-recovery to permethrin in the populations studied was demonstrated. This should be taken into account before introducing these insecticides to control populations of Ae. aegypti in the region.

Effects of cow ghee (clarified butter oil) & soybean oil on carcinogen-metabolizing enzymes in rats.

Background & objectives: Our previous study showed that cow ghee relative to soybean oil had a protective effect against carcinogen induced mammary cancer in rats. The objective of this study was to elucidate its biochemical mechanism. Methods: Two groups of 21 day old rats (20 each) were fed for 44 wk diet containing cow ghee or soybean oil (10%). Five animals from each group were sacrificed at 0 day and at 5, 21 and 44 wk for analysis of phase I and phase II pathways enzymes of carcinogen metabolism. Results: Dietary cow ghee relative to soybean oil decreased the activities of cytochrome P450 (CYP) enzymes, CYP1A1, CYP1A2, CYP1B1 and CYP2B1, responsible for activation of carcinogen in liver. Carcinogen detoxification activities of uridinediphospho-glucuronosyl transferase (UDPGT) and quinone reductase (QR) in liver, and γ-glutamyltranspeptidase (GGTP) and QR in mammary tissue were significantly higher in cow ghee fed rats than in soybean oil fed rats. The hepatic GGTP activity decreased on soybean oil diet; while in cow ghee group it remained unaffected. Interpretation & conclusions: Our findings show that dietary cow ghee compared to soybean oil downregulates the enzyme activities responsible for carcinogen activation in liver and upregulates carcinogen detoxification activities in liver and mammary tissues.