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Pharmacometabolomic analysis of rat hippocampus and plasma in response to chronic stress and albiflorin treament

ABSTRACT: Male Sprague-Dawley (SD) rats were exposed to one random stressor per day for 35 d. Following four weeks of stress exposure, rats with stress-induced depression-like behaviors were treated daily with either saline, fluoxetine or albiflorin for 7 days via intragastric gavage. Rat heparinized plasma was collected after drug treatment. After behavior tests, rats were sacrificed and the hippocampus was collected. Pharmacometabolomic analysis was conducted for both plasma and hippocampal samples

ORGANISM(S): Rat Rattus Norvegicus

TISSUE(S): Blood

DISEASE(S): Stress

SUBMITTER: Zuoguang Zhang

PROVIDER: ST000903 | MetabolomicsWorkbench | Thu Nov 16 00:00:00 GMT 2017

REPOSITORIES: MetabolomicsWorkbench

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Project description:Chronic obstructive pulmonary disease (COPD) is diagnosed by airway obstruction and underlies a group of ailments such as bronchitis, emphysema and often asthma; however, rodent models do not resemble human pathology. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, thrombosis, oxidative stress, and suppressed immune function, that are also apparent in COPD patients, we exposed SH and commonly used male Sprague Dawley (SD) to 0, 250, or 350 ppm sulfur dioxide (SO2), 5h/d for 4 consecutive days. Airways disease was characterized by pulmonary functional, pathological and molecular analysis. SO2 caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD. Bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose-dependent and significantly greater in SH than in SD rats. The recovery was incomplete 4-day following SO2 exposure in SH rats. Pulmonary protein leakage did not occur in either strain but lactate dehydrogenase and n-acetyl glucosaminidase activity was increased in BALF of SH rats. Lung pathology and morphometric evaluation of mucin production in the airways demonstrated significantly greater impact of SO2 in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, and impairment cell signaling and fatty acid metabolism in SH rats. Gene expression pattern of SD and SH rats following SO2 exposure demonstrated greater effect on inflammation/immune markers, and oxidative stress. Thus, the SH rat may serve as a better and more susceptible rat strain to be used for experimental model of bronchitis which is relevant to human disease. Experiment Overall Design: Spontaneously hypertensive and Sprague Dawley rats were used in this experiment. Each strain of rat was treated with either SO2 or AIR (control). There were 4 biological replicates for each strain/treatment.

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Pharmacometabolomic analysis of rat hippocampus and plasma in response to chronic stress and albiflorin treament

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