Phytochemical 3,3'-Diindolylmethane Prevents the Onset of Hypoxia

Hypoxia is a condition of deficiency in the amount of oxygen reaching the tissues, leading to permanent damage to the brain, liver, and other organs.

The most common symptoms of hypoxia include fast heart rate, rapid breathing, shortness of breath, slow heart rate and sweating.

Hypoxemia is a condition of the abnormally low level of oxygen in the blood.

There are many risk factors associated with the onset of hypoxemia, including reduced oxygen levels on the high altitude, damage of the lung that affects the breathing and exhaling function.

People with lung and heart disease such as asthma, poor blood circulation, and anemia are at a higher risk of hypoxemia.

3,3'-Diindolylmethane or DIM are phytochemicals derived from the digestion of indole-3-carbinol, belonging to the group of Indoles, found abundantly in broccoli, Brussels sprouts, cabbage, and kale, etc.

In searching a potential compound against the onset of hypoxia, researchers examined the neuroprotective potential of 3,3'-diindolylmethane (DIM) in cellular and animal models of Parkinson's disease and lipopolysaccharide-induced inflammation.

In hypoxia-induced damage in mouse hippocampal cells in primary cultures, the 18 h of hypoxia-induced apoptotic processes in terms of the mitochondrial membrane potential, associated with the process of energy storage during oxidative phosphorylation. activation of a protein associated with cell death induced by fragmentation of cell nuclei.

Injection the DIM significantly demonstrated strong neuroprotective and anti-apoptotic actions in hippocampal cells exposed to hypoxia through decreasing the expression genes (Ahr and Arnt) involved the regulation of inflammatory signaling pathways and increasing the gene (Erβ) expression involved suppressing the inflammatory responses.

Furthermore, DIM decreased the expression of AhR-regulated CYP1A1 in stimulating the inflammatory response.


The results strongly suggested impairment of protein expression of AhR and ARNT, but not ERβ plays a key role in the neuroprotective action of DIM against hypoxia-induced cell damage.

Where aryl hydrocarbon receptor nuclear translocator (ARNT) is a component of the DNA binding form of the Ah receptor required for receptor function.

And aryl hydrocarbon receptor (AhR) is a protein associated with the regulation of gene expression.

In other words, the mutation of genes aryl hydrocarbon receptor (AhR) or aryl hydrocarbon receptor nuclear translocator (ARNT) are the culprits in the induction of neuro oxygen deficiency.


Based on the findings, researchers wrote in the final report, "This study may have implications for identifying new agents that could protect neurons against hypoxia by targeting AhR/ARNT signaling".

Furthermore, hypoxia induces oxidative damage in retinal pigment epithelial cells (RPE cells) by cobalt chloride (CoCl2, 200 µM) and/or DIM (10 and 20 µM). DIM significantly attenuated the CoCl2-induced expression of a protein (VEGF) associated with the formation of blood vessels in the ARPE-19 cells compared to the lower levels under normal conditions.

Similar to those of the aforementioned characteristics, DIM deactivated the genes which play an integral role in the body's response to low oxygen concentrations (HIF-1α) and pro-apoptosis (NF-κB, p38 MAPK) induced by CoCl2.

DIM also inhibited the induction of hypoxia by CoCl2 through the inhibition of oxidative stress detected by fluorescence microplate assay.

Taken altogether, 3,3'-Diindolylmethane derived from the digestion of indole-3-carbinol may be considered a supplement for the prevention of hypoxia, pending to the confirmation of the larger sample size and multicenter human study.

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) Selective Aryl Hydrocarbon Receptor Modulator 3,3'-Diindolylmethane Impairs AhR and ARNT Signaling and Protects Mouse Neuronal Cells Against Hypoxia by Rzemieniec J1, Litwa E1, Wnuk A1, Lason W1, Krzeptowski W2, Kajta M. (PubMed)
(2) 3,3'-Diindolylmethane inhibits VEGF expression through the HIF-1α and NF-κB pathways in human retinal pigment epithelial cells under chemical hypoxic conditions by Park H1, Lee DS2, Yim MJ2, Choi YH3, Park S4, Seo SK4, Choi JS5, Jang WH6, Yea SS6, Park WS7, Lee CM8, Jung WK9, Choi IW. (PubMed)