EXCLI Journal

Evaluation of organophosphorous pesticide triazophos induced immunotoxicity of spleen and head kidney in fresh water teleost, Channa punctatus

2020-10-31T07:06:44+01:00

Utilization of pesticides has increased for destroying pest and protection of crops in agriculture field. Triazophos is a commonly used organophosphorous insecticide that causes paralysis and death of insect by accumulating the neurotransmitter acetylcholine in synapse which leads to continuous flow of neuromuscular signals. Present study was designed to evaluate the effect of triazophos induced innate and cell mediated immunotoxicity in fresh water teleost, Channa punctatus. Fishes were exposed to triazophos at concentrations 5 and 10 % of LC₅₀ value for 10 and 20 days. Splenic and head kidney macrophage phagocytosis, nitric oxide production and superoxide production were assayed to evaluate the innate immunity. Cell mediated immunity was measured through splenic and head kidney lymphocyte proliferation in presence of T and B cell mitogens. Results of the present study revealed that macrophage phagocytosis was significantly reduced after in vivo triazophos treatment. Differential suppressive effect of triazophos was also observed where mitogen induced splenic and head kidney lymphocyte proliferations were reduced after 10 and 20 days treatment. Concentration dependent effect of triazophos was observed in vivo studies where production of reactive oxygen and nitrogen intermediates were suppressed. This study describes the first investigation of the effect of triazophos on immune functions and will help to determine appropriate ecotoxicity and immunotoxicity in fresh water teleosts.

Immunology of IL-12: An update on functional activities and implications for disease

2020-10-30T10:52:47+01:00

As its first identified member, Interleukin-12 (IL-12) named a whole family of cytokines. In response to pathogens, the heterodimeric protein, consisting of the two subunits p35 and p40, is secreted by phagocytic cells. Binding of IL-12 to the IL-12 receptor (IL-12R) on T and natural killer (NK) cells leads to signaling via signal transducer and activator of transcription 4 (STAT4) and subsequent interferon gamma (IFN-γ) production and secretion. Signaling downstream of IFN-γ includes activation of T-box transcription factor TBX21 (T-bet) and induces pro-inflammatory functions of T helper 1 (T_H1) cells, thereby linking innate and adaptive immune responses. Initial views on the role of IL-12 and clinical efforts to translate them into therapeutic approaches had to be re-interpreted following the discovery of other members of the IL-12 family, such as IL-23, sharing a subunit with IL-12. However, the importance of IL-12 with regard to immune processes in the context of infection and (auto-) inflammation is still beyond doubt.

In this review, we will provide an update on functional activities of IL-12 and their implications for disease. We will begin with a summary on structure and function of the cytokine itself as well as its receptor and outline the signal transduction and the transcriptional regulation of IL-12 secretion. In the second part of the review, we will depict the involvement of IL-12 in immune-mediated diseases and relevant experimental disease models, while also providing an outlook on potential translational approaches.

Moderate-intensity exercise improves endothelial function associated with altered gut microbiome composition in rats fed a high-fat diet

2020-10-30T09:27:27+01:00

Obesity alters gut microbial ecology, and exercise is effective in preventing obesity. There is an association between gut microbial and endothelial dysfunction in patients with obesity. However, the underlying mechanisms through which exercise improves endothelial function in obese individuals have not been fully elucidated. This study was performed to investigate whether physical exercise improves endothelial function and alters gut microbiome composition in rats fed a high-fat diet (HFD) to induce obesity. Male Sprague Dawley rats were divided into four groups, which included the non-exercise and standard diet (SD control) group, the exercise and standard diet (SD trained) group, the non-exercise and HFD (HF control) group, and the exercise and HFD (HF trained) group. Obesity was induced by a HFD for eleven weeks. The rats in the exercise groups were subjected to a moderate-intensity exercise training on a treadmill for eight weeks. The whole-body composition and endothelium-dependent relaxation of mesenteric arteries were measured. Blood biochemical tests were performed, and gut microbiomes were characterized by 16S rDNA gene sequencing on an Illumina HiSeq platform. Correlation analysis was used to detect any associations between body composition or endothelial function parameters and gut microbiome composition. Exercise training for eight weeks was effective in improving body composition in HFD-fed rats. Furthermore, compared with the HF control group, aerobic exercise significantly increased acetylcholine-induced, endothelium-dependent relaxation in mesenteric arteries (P < 0.05), and circulating vascular endothelial growth factor levels (P < 0.01), and decreased circulating C-reactive protein levels (P < 0.05). In addition, exercise and HFD led to alterations in gut microbiome composition. Exercise decreased the relative abundance of Romboutsia and Clostridiales. Additionally, Pearson’s correlation analysis showed that Ruminococcus_2 and Ruminococcus_gnavus_group were closely related to body composition parameters. Moreover, twelve species of bacteria, including Romboutsia, were significantly related to endothelial function parameters in the total subject population. These results suggest that aerobic exercise improves endothelial function and that this change is associated with altered gut microbiota composition in HFD-fed rats, providing new insights into the use of physical exercise for improving endothelial function in people with obesity.