Today lets focus on a hormone that many of you might be familiar with due to its involvement in helping us fall asleep. This hormone is called N-acetyl-5-methoxy tryptamine, or as you may know it by the less chemical name, Melatonin.

The structure of melatonin, in case you were curious

Melatonin is a hormone produced by a small gland in our brains called the pineal gland and is as I said above, important for regulating our sleep/wake cycle (it signals to your brain that its sleepy time). The pineal gland is also thought to be involved in secreting compounds which regulate hormone secretion from another gland called the pituitary gland (this is where the sex hormones come from), but I digress.

A new publication in the journal PLoS One titled "Melatonin protects rats from radiotherapy-induced small intestine toxicity" , this article focuses on the authors reporting on melatonin's involvement in protection against Mucosis.

What Is Mucosis?

Mucosis is the term given to the inflammation and break down of the walls of our digestive tract as a result of chemotherapy or radiotherapy treatments for cancer. This condition is painful, and surprisingly common during cancer treatments (upwards of 15% of patients experience mucosis, somewhere in their digestive tract's[2] ). Unfortunately for these sufferers, there is no known treatment for the disorder, so patients must suffer with pain and digestive issues during the course of their treatments (and potentially beyond).

Melatonin is reported to have anti-inflammatory properties and has been previously been shown to have a protective effect against oral mucosis (the breakdown of the tissues of the mouth) during radiation therapy [3]. So there is some precedent to it having a benefiticial protective effect against this disorder.

Here The Authors Were Looking At The Intestine

The articles authors were looking to see whether or not this protective effect extended to mucosis in other areas of the gastro-intestinal tract, and so they investigated the intestines.

They followed the scheme outlined in the image above, where for each day over the course of 20 days rats were either given (or not) 45 mg melatonin each day (labeled aMT) and for each of days 2-7 the rats were exposed to 7.5 Greys of radiation each day (this adds up to 45 Greys, which is a common amount of radiation exposure during a cancer treatment 40-60 greys is typically used, these numbers are quite large, but you must also keep in mind that they are targeted to specific areas, this is not whole body exposure amounts). After 21 days samples of the rats intestines were harvested and examined.

What Did They Find?

Some promising results, thats what. Lets take a look at a little bit:

So here we are looking at swatches of the small intestine from three different rat sub-types. On the left is from a control rat, not exposed to any radiation. The middle is a rat exposed to the radiation but not given melatonin, and the right is exposed to radiation with the daily 45 mg melatonin supplementation (in a oral gel form). What the authors are looking at here are the intestinal villi (which are the projections that increase the surface area of our intestine and allow for lots of regions to absorb nutrients and for the intestinal bacteria to live.

What you can see is that the radiation results in destruction of the intestinal villi, but supplementation with melatonin, results in villi that look more like the control. The authors also reported a bar-graph depicting the villi length which illustrates this protective trend perhaps more clearly:

The authors did not only look at this from a intestinal structure perspective

The authors also report on several other indicators of damage from radiation exposure including oxidative stress. They looked at this through determining the expression levels of a protein called zonula occludens-1 (ZO-1) which in cells adhering to one another, during times of oxidative stress the expression of this protein goes down and it serves as a marker for that state.

Above is a plot where the intestinal cells were stained to detect ZO-1, and we can see that the amount of this protein around decreases with exposure to the radiation, but when the rats were supplemented with Melatonin, it appears to be restored to near control levels.

Other Results Reported

• Decreased mitochondrial functioning results in an increased production of radical oxygen species. Melatonin was observed to protect against mitochondrial damage in the mice, authors explored through western blotting the expression levels of several proteins including Glutathione Peroxidase -1 (GPx1), glutathione reductase (GRd). The production of these proteins was reduced in the mice exposed to radiation, but restored to control levels in the mice supplemented with the melatonin.

• Melatonin inhibited the expression of proteins involved in the inflammatory response (NLRP3 ) that occurs when exposed to radiation

• Melatonin stopped cellular apoptosis in the intenstines of the mice when exposed to radiation

• The authors supplementation of Melatonin resulted in drastically increased concentrations of it being present in the intestinal cells of the mice, providing evidence in favor that the above reported positive effects were truly due directly to the presence of the melatonin, and that it was in fact reaching the small intestines in concentrations high enough to be protective:

Conclusions

Exposure to radiation results in damage to the small intestine and causes the disease mucosis. Melatonin, at least in this rat model, appears to provide protection to the small intestine (and mouth in a previous study) against mucosis. This study is compelling evidence that melatonin should be a candidate for exploration in humans as well.

This could help alleviate some of the suffering of a lot of people undergoing cancer treatments.

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Sources

1. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174474
2. http://onlinelibrary.wiley.com/wol1/doi/10.1002/cncr.20163/abstract
3. http://onlinelibrary.wiley.com/doi/10.1111/jpi.12191/abstract

All Non Cited Images Are From Pixabay.com And Are Available Under Creative Commons Licenses

Any Gifs Are From Giphy.com and Are Also Available for Use Under Creative Commons Licences

Images from figures in PLoS One articles are available for reuse under a Creative Commons license.

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