Measuring Oxidative Stress May Help to understand health and disease

Richard Meitern studied in his Doctoral thesis, defended at the University of Tartu, whether some of the popular methods currently available can be used to reliably measure oxidative stress. Source:
Richard Meitern studied in his Doctoral thesis, defended at the University of Tartu, whether some of the popular methods currently available can be used to reliably measure oxidative stress. Source:

While people generally think of oxygen as something that is essential for life, then actually, oxygen is also a poisonous gas, for it reacts readily with various substances. Richard Meitern studied in his Doctoral thesis, defended at the University of Tartu, whether some of the popular methods currently available can be used to reliably measure oxidative stress.

What would change in the world, however, if scientists could measure oxidative stress accurately, was explored by the Tartu University magazine Universitas Tartuensis.

Meitern commented to have studied something that is extremely hard to measure and the objective of his Doctoral thesis was to evaluate, whether some of the popular biomarkers, used up to now for scientific purposes, are enough.

Oxidative stress is a situation in the organism, where the internal balance between reactive oxygen species and antioxidants is disturbed. Excessive oxidative stress may cause or worsen various diseases, such as cancer, diabetes, neurodegenerative diseases etc.

Meitern studied, whether some popular techniques for assessment of oxidative stress are suitable for studies of birds that live freely in the natural environment. It is thought that oxidative stress may occur in situations, where the organism is under strain, meaning that the muscles have higher workload than usual, resulting in higher oxygen consumption. “Secondly, when the immune system is fighting pathogens, the same reactive oxygen particles that are fighting the disease may also harm the host.”

Damage related to everyday activities is what measuring of oxidative stress is trying to identify. According to Meitern, living is an activity that is wearing out the organism, but the body is constantly fighting this by continuous renewal of tissues. “And actually, it is possible that the damage resulting from reacting with oxygen, for example, is not pertinent to determining the future, i.e. the quality of life in the future.”

It is possible that in a normal situation, oxidative stress causes no symptoms. It may, however, play an important role in relation to specific diseases, where the number of reactive particles increases steeply, e.g. due to a gene defect.

“Therefore, one possibility is that oxidative stress is harmful. My work rather indicates that there is another possibility, according to which oxidative stress does not play as a significant role as thought up to now. Oxygen has existed in the world for a very long time and organisms have adapted to cope with the negative effects of breathing oxygen.” Thus, damages occur but in ordinary conditions, the body is able to repair these damages.

The measure that is not accurate

In an article that formed a part for his research, Meitern concentrated on validating a widely-used method – the d-ROMs test that evaluates oxidative damage.

“This test has been criticised before, but lately, it has been widely used in ecological studies involving birds. We tried to determine, how reasonable is the use of this assay, and how much other substances present in the blood serum distort the results.”

It was discovered that the results can be affected by many other factors, and determining the relative importance of those different factors is virtually impossible at this time.

To test the d-ROMs test, European greenfinches were captured in early winter and blood samples were obtained from the birds. To include more species, chicken and human blood samples were used as well. “We were aware that the test is designed to measure Fenton’s reaction and that blood contains substances that may affect its results.” Therefore, it was tested how different substances present in blood influence the measuring results.

Meitern explained that markers that indicate immune system activation tend to correlate with the dROMs test results. “We tried different test conditions to get a better grasp of whether it is possible to measure only oxidative damage.” Different substances were added to blood serum, temperature of the test environment was changed, etc., but it was still found that oxidative damage cannot be measured with the dROMs test reliably. “Too many factors affect the test results,” concluded Meitern.

Large impact of chemical stress

In another part of the thesis, oxidative stress was chemically induced in a small number of birds, i.e., they were administrated the substance that causes oxidative stress. “It is often very hard to determine, whether a specific situation causes oxidative damage or not. Therefore, we induced oxidative stress with paraquat.” Next, the researchers evaluated the extent to which the oxidative stress induced in birds is reflected in different biomarkers.

Meitern said to have constantly observed, how this manipulation affected the birds. When the oxidative stress level was low, none of the tested measuring methods detected it. “In case of severe oxidative stress, however, the birds’ health deteriorated significantly – their body mass dropped considerably and we noticed the emergence of DNA damages as well.” The experiment was discontinued, when the loss of body mass became too high.

Besides that, it was also tested how scaring the birds affected some of those biomarkers of oxidative stress.

“We found that there is rather no clear change in the levels of the relevant measures. It is possible that the biomarkers being used are either unsuitable or insufficient.” Meitern added that the system to counteract harmful effects of oxygen has been evolving over millions of years and is simply too complicated for full comprehension.

Oxidative stress as a link

Organisms have to choose how to allocate their resources. “For example, animals are engaged with foraging, tissue renewal, reproduction, etc. – all these activities require resources. In addition to visible resource allocation, there are many other processes that use resources but are invisible, such as those spent on maintaining the immune system.”

If the body is fighting a pathogen, resources are allocated to this process. “It is thought that oxidative damage and stress redistribute resources on one or another process. If a person is fighting pathogens, many reactive particles are formed that are damaging the body.” Therefore, the organ system must invest in repairing the body and less energy remains for other activities.

“Our idea is namely to determine, how these different vital situations and events that the body has to deal with relate to and influence each other. It has been argued that oxidative stress is a kind of link between them.”

Currently, there is no perfect biomarker for measuring oxidative stress. If it existed, however, we might get a better understanding of how the body decides to distribute energy between different activities and whether oxidative stress has any relevance in this process.

“If stress could be measured reliably, we would maybe find out how to improve the situation – how to keep the production of reactive particles under control. Then, we could maybe get more energy, keep the damage under control more efficiently, and maybe enjoy a longer life expectancy.”

Meitern comments that today, there is much talk that people need to eat various antioxidants. “Unfortunately, the benefit of antioxidant dietary supplements have not been clinically proven. If you look at the recommendations of the World Health Organisation, for example, you will not find antioxidant supplements in their list, because their benefit is undetermined.”

It is known that people are constantly searching for a miracle cure to live longer and better, but Meitern suggests that there is no universal key to open all the doors. “It is the same with oxidative stress. It is considered important, but we actually do not know how important it is, and measuring it is also complicated. If we were able to comprehend, whether oxidative stress is an important part of everyday life, we could also understand, whether people’s lives could improve if we manipulated it.”

On 1 February, Richard Meitern defended his Doctoral theses “Redox physiology of wild birds: validation and application of techniques for detecting oxidative stress” at the Chair of Animal Ecology of the University of Tartu. The supervisor was Professor Peeter Hõrak and the opponent was Professor John R. Speakman from the University of Aberdeen in Scotland.

The translation of this article from Estonian Public Broadcasting science news portal Novaator was funded by the European Regional Development Fund through Estonian Research Council.