Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed t
... Show MoreStaphylococcal enterotoxin‐B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing a cytokine storm. Inhaled SEB can cause acute respiratory distress syndrome (ARDS), which is often fatal and with no effective treatments.
Efficacy of Δ9‐tetrahydrocannabinol (THC) was tested in a mouse model of SEB‐mediated ARDS, in which lung inflammation, alterations in gut/lung microbiota and production of short‐chain fatty acids (SCFAs) was measured. Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. F
Studies from our laboratory have shown that Δ9-Tetrahydrocannabinol (THC), an ingredient found in marijuana plant Cannabis sativa, can attenuate acute lung injury induced by Staphylococcus enterotoxin B (SEB). In the current study, we investigated the role of THC on the metabolism of SEB-activated lymphocytes. To this end, we determined metabolic potential of SEB-activated lymphocytes treated with vehicle or THC by performing the Cell Mito Stress Test. The oxygen consumption rate (OCR) in THC-treated cells was decreased when compared to vehicle-treated group whereas the extracellular acidification rate (ECAR) was similar in both the groups. Specifically, electron transport chain inhi
Inhalation of Staphylococcal Enterotoxin B (SEB) is known to induce acute lung injury (ALI) and studies from our laboratory have shown that THC, a psychoactive ingredient found in Cannabis sativa, can attenuate the ALI. In the current study, we investigated the role played by lung microbiota in ALI with or without THC treatment. A dual-dose of SEB was given to C3H/HeJ mice, which were then treated either with vehicle or THC. SEB-administration caused ALI and 100% mortality while all THC-treated mice survived and suppressed the inflammation in the lungs. Furthermore, lung microbiota was collected and 16S rRNA sequencing was performed. The data were analyzed to determine the alpha and b
Acute respiratory distress syndrome (ARDS) is defined as a type of respiratory failure that is caused by a variety of insults such as pneumonia, sepsis, trauma and certain viral infections. In this study, we investigated the effect of an endocannabinoid, anandamide (AEA), on ARDS induced in the mouse by
Multiple Sclerosis (MS), is a common autoimmune disease that affects the central nervous system. Currently, there is no cure for MS, and most treatments involve the use of immunosuppressive drugs that can have adverse effects or increased toxicity. Cannabis, commonly known as marijuana, is a product of the Cannabis sativa, and for several centuries has been used as an alternative medicine in many cultures. Cannabis sativa produces over 421 chemical compounds, including about 80 terpenophenols named phytocannabinoids, and include both psychotropic THC and non-psychoactive CBD. In the currently study, we show that a combination therapy using THC and CBD results in amelioration of EAE, a
Acute toxicity is a step to evaluate the toxicity of a substance. Rutin is one of the flavonoid compounds with a variety of pharmacological effects. The aim of the study is to calculate the lethal dose that affect fifty percent of the mice used in the experiment (LD50). Thirty Swiss albino male and 30 non-pregnant female mice have been divided equally and randomly into 5 treated groups and one control group (n=5) Rutin has been administered with concentrations 5, 2.5.1.25,0.625 and 0.312 g/kg administered as a single dose intraperitoneally (IP) while the control group received 1% DMSO (IP). Animals were observed for any morbidity and mortality for 14 days. After 14 days the animal blood collected for biochemical and hem
... Show MoreResveratrol, (RES), a phytoalexin, is well-known for its anti-inflammatory and anti-oxidant properties. SEB, a superantigen, is known to trigger ALI and cause mortality. In the current study, we tested the effect of RES in a dual-dose model of SEB exposure that triggers ALI and causes 100% mortality in C3H/HeJ-mice. The data revealed RES attenuated SEB-induced ALI and prevented mortality. Forty eight hours post-SEB exposure, lung-infiltrating mononuclear cells were tested for microRNA expression profile to determine the epigenetic regulation by resveratrol. SEB-activated splenocytes were pre-treated with 50 μM of RES or vehicle for metabolic profile analysis by measuring oxygen consu
Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq)
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