Oxidation in the Body: What It Is, Advancements in Diagnosis and Antioxidants

If you follow Hemopet’s posts about companion animal health, one of the resounding themes is balance. For instance, vitamin D deficiency can lead to many chronic health conditions like cancer, but an abundance can cause a toxicity that can lead to other health problems such as kidney dysfunction. We’ve also discussed the delicate balance of adding pumpkin to your companion dog’s diet to prevent bottom scooting. We could go on and on…So, let’s discuss oxidation.

Oxidation in the body creates a byproduct called reactive oxygen species (ROS) that could function as free radicals or eventually produce free radicals. This is actually a very natural process. ROS in immune cells can help combat invading pathogens such as viruses, bacteria, and fungi. Thus, some ROS have antimicrobial properties, because it is an acute state of oxidative stress (OS) that can be beneficial.

On the flip side, an overabundance of ROS can accelerate aging leading to acute states of OS such as strokes, or to chronic diseases such as cancer, cardiovascular, periodontal, or metabolic disorders. 

In essence, there is an imbalance of ROS in relation to the antioxidants in the body. 

As you might expect, many researchers point out that therapeutic antioxidants can prevent the ROS functions that promote tumor formation. 

Indeed, it is a delicate balance. 

However, what we know is that ROS are disproportionately more abundant these days than antioxidants in the bodies of humans and animals. 

Oxidation of cells is naturally occurring in the body, but overall oxidation is becoming increasingly influenced by outside factors such as environmental pollutants, heavy metals, certain drugs, chemical solvents, cooking (smoked meat, used oil, and fat), cigarette smoke, alcohol, and radiation exposure – all of which leads to chronic health problems. 

Oftentimes when we think of oxidizing cells, we think of our upper bodies or the vital organs like the heart and lungs there. However, the most important oxidation processes occur in the gut. The building blocks of life are all prone to oxidation: lipids (fat); proteins and amino acids; and, saccharides (carbohydrates). 

Measuring Oxidation

So, how do we measure ROS in the body that may indicate an overabundance that causes OS? 

Remember: oxidation can occur in or impact immune cells, DNA, proteins, amino acids, lipids and carbohydrates. 

Hemopet’s Hemolife Laboratory, in conjunction with Oxford Biomedical Research, has studied and developed a test called CellBIO that measures the level of isoprostane in dog saliva – a byproduct of the oxidation of lipids (known as lipid peroxidation) – that is catalyzed or propelled by ROS. Isoprostanes serve as markers of oxidative damage. So, we are not looking at the ROS directly, but at the end result that indicates an overabundance of harmful ROS.

Experiments Using Oxidation

At Hemopet, we are interested in the work coming out of Dr. Dodds’ alma mater at the University of Guelph that is using the indicator amino acid oxidation (IAAO) technique to determine the appropriate amounts and balances of amino acids in companion dog food. 

We know, you are thinking, “Oxidation! How could they?” Actually, the IAAO technique is minimally invasive and short-term. The technique is a very useful indicator to assess whether a longer study is needed.

If you have been following our blog regarding dilated cardiomyopathy (DCM) in dogs, you’ll know where this inquiry is heading.

For background, the amino acids methionine and cysteine are used by the liver to create another amino acid, taurine – which is essential for heart health in dogs and cats. A deficiency of taurine can lead to DCM, a complex disease. Both methionine and cysteine are highly susceptible to oxidation, which makes them excellent for this test. 

We have known about breeds that are susceptible to inherited forms of DCM. Many of the breeds are larger breeds. For years, researchers have studied various food combinations to see if one might inhibit taurine production or its uptake in a particular breed, or if the foods have enough methionine and cysteine to achieve taurine homeostasis as measured in whole blood or plasma.

What makes the University of Guelph experiments unique is that they are comparing the amino acid requirements of three different breeds – Miniature Dachshunds, Beagles and Labrador Retrievers – which importantly fall into different weight classes.

At first, they gave the dogs diets deficient in methionine with an excess of cysteine and then measured breath samples for CO2 (carbon dioxide). The premise is that if methionine is deficient, it is not being utilized at all, and is subsequently being oxidized and released in breath. Breath measurement is a cornerstone of the IAAO technique that has been used with species such as humans, pigs, rats, chickens. As the study team increased the methionine present in the diet, the CO2 levels decreased to optimum levels in order to determine the proper amount for each breed. What they concluded is that the methionine requirement for Beagles and Labrador Retrievers was greater than that recommended by the National Research Council (NRC), whereas the NRC requirement was similar to that estimated for Miniature Dachshunds. 

Combatting Oxidation with Antioxidants

Cellular oxidation, and the amounts of oxidants and antioxidants, all need to be balanced. 

However, realistically, many commercial companion pet foods on the market do not focus on adding foods rich in antioxidants and they probably do not have enough to combat accelerated aging. Why? Perhaps because the Association of American Feed Control Officials (AAFCO) has not made it a priority. 

A groundbreaking study from Fahnestock et al. found that a combination of environmental enrichment and antioxidant dietary intervention can increase brain-derived neurotrophic factor (BDNF) mRNA in aged animals to levels approaching those seen in young dogs. 

So, what do we do? If you test your companion dog with CellBIO, we can suggest enrichments to his diet. 

Another idea is one we regularly encourage all companion dog parents to do: start treating your companion dog with fresh or steamed vegetables, shaved almonds, or fresh fruits to easily add antioxidants to their diets. 

References 

Auten, Richard L, and Jonathan M Davis. “Oxygen Toxicity and Reactive Oxygen Species: The Devil Is in the Details.” Pediatric Research, vol. 66, no. 2, Aug. 2009, pp. 121–127, doi:10.1203/pdr.0b013e3181a9eafb, https://www.nature.com/articles/pr2009174

Becker, Karen. “How Antioxidants Work to Reduce Oxidative Stress.” HealthyPets, Mercola, 1 Nov. 2020, https://healthypets.mercola.com/sites/healthypets/archive/2020/11/01/antioxidants-for-pet.aspx

Dodds, W. Jean. “Biomarkers of Oxidative Stress in Dogs.” Medical Research Archives, vol. 8, no. 5, 5 May 2020, doi:10.18103/mra.v8i5.2112, https://esmed.org/MRA/mra/article/view/2112

Elango, Rajavel, et al. “Indicator Amino Acid Oxidation: Concept and Application.” The Journal of Nutrition, vol. 138, no. 2, 1 Feb. 2008, pp. 243–246, doi:10.1093/jn/138.2.243, https://academic.oup.com/jn/article/138/2/243/4664973

Elango, Rajavel, et al. “Recent Advances in Determining Protein and Amino Acid Requirements in Humans.” British Journal of Nutrition, vol. 108, no. S2, 2012, pp. S22–S30, doi:10.1017/S0007114512002504, https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/recent-advances-in-determining-protein-and-amino-acid-requirements-in-humans/FBFB18EF9B97F7ED3EF92910D6CE4E57

Fahnestock, Margaret et al. “BDNF increases with behavioral enrichment and an antioxidant diet in the aged dog.” Neurobiology of Aging, vol. 33, no. 3 (2012): 546-54, doi:10.1016/j.neurobiolaging.2010.03.019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935515/

Harrison, Matthew, et al. “Short-Term Determination and Long-Term Evaluation of the Dietary Methionine Requirement in Adult Dogs.” British Journal of Nutrition, vol. 123, no. 12, 2020, pp. 1333–1344, doi:10.1017/S0007114520000690, https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/shortterm-determination-and-longterm-evaluation-of-the-dietary-methionine-requirement-in-adult-dogs/0CD64220859D72BD77C12B2D2EECC206

Hawkins, Clare L., and Michael J. Davies. “Detection, Identification, and Quantification of Oxidative Protein Modifications.” Journal of Biological Chemistry, vol. 294, no. 51, Dec. 2019, pp. 19683–19708, doi:10.1074/jbc.rev119.006217, https://www.jbc.org/article/S0021-9258(20)30281-7/fulltext

Hayamizu, Kohsuke et al. “Estimation of inter-individual variability of protein requirement by indicator amino acid oxidation method.” Journal of Clinical Biochemistry and Nutrition, vol. 68, no. 1 (2021): 32-36, doi:10.3164/jcbn.20-79, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844655/

Liou, Geou-Yarh, and Peter Storz. “Reactive oxygen species in cancer.” Free radical research vol. 44, no. 5 (2010): 479-96, doi:10.3109/10715761003667554, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880197/

Lobo, V et al. “Free radicals, antioxidants and functional foods: Impact on human health.” Pharmacognosy Reviews, vol. 4, no. 8 (2010): 118-26, doi:10.4103/0973-7847.70902, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249911/

Mansilla, Wilfredo D, et al. “Minimum Dietary Methionine Requirements in Miniature Dachshund, Beagle, and Labrador Retriever Adult Dogs Using the Indicator Amino Acid Oxidation Technique.” Journal of Animal Science, vol. 98, no. 11, 5 Oct. 2020, doi:10.1093/jas/skaa324, https://academic.oup.com/jas/article/98/11/skaa324/5917805

Phaniendra, Alugoju et al. “Free radicals: properties, sources, targets, and their implication in various diseases.” Indian Journal of Clinical Biochemistry, vol. 30, no. 1 (2015): 11-26, doi:10.1007/s12291-014-0446-0, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310837/

Pizzino, Gabriele et al. “Oxidative Stress: Harms and Benefits for Human Health.” Oxidative Medicine and Cellular Longevity, vol. 2017 (2017): 8416763, doi:10.1155/2017/8416763, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551541/

Shields, Hazel J., et al. “Beneficial and Detrimental Effects of Reactive Oxygen Species on Lifespan: A Comprehensive Review of Comparative and Experimental Studies.” Frontiers in Cell and Developmental Biology, vol. 9, 11 Feb. 2021, doi:10.3389/fcell.2021.628157, https://www.frontiersin.org/articles/10.3389/fcell.2021.628157/full

Suto, Daisuke, et al. “Structural Analysis of Amino Acids, Oxidized by Reactive Oxygen Species and an Antibody against N-Formylkynurenine.” Journal of Clinical Biochemistry and Nutrition, vol. 38, no. 2, 23 Feb. 2006, pp. 107–111, doi:10.3164/jcbn.38.107, https://www.jstage.jst.go.jp/article/jcbn/38/2/38_2_107/_article/-char/en

Templeman, James R, et al. “Tryptophan Requirements in Small, Medium, and Large Breed Adult Dogs Using the Indicator Amino Acid Oxidation technique.” Journal of Animal Science, vol. 97, no. 8, 25 Apr. 2019, pp. 3274–3285, doi:10.1093/jas/skz142, https://academic.oup.com/jas/article-abstract/97/8/3274/5479477.

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