Vegetable extracts for reducing lung damage in premature babies

Tec researchers tackle bronchopulmonary dysplasia in premature babies, a disease they acquire when exposed to high concentrations of oxygen.

Of the more than 130 million births a year in the world, 11.1% are premature, meaning they are born before the 37th week of gestation.

When born prematurely, premature babies have different characteristics, such as lower weight, problems feeding and difficulty breathing, but one of the pathologies that commonly present is bronchopulmonary dysplasia. This disease is generated by an alteration in the lung development of both the airways and the pulmonary vessels, and is the main cause of chronic disease and morbidity in these babies. 
 

Why are premature babies prone to lung damage?

Under normal conditions, the oxygen concentration we breathe is 21%, but premature babies are usually exposed to much higher concentrations, as part of the management of respiratory failure that they frequently present at birth, as well as being at risk of having periods of hypoxia (that is, a state of oxygen deficiency in the blood).

Although exposure to high concentrations of oxygen increases the survival of babies, it also produces negative effects on various organs, including the lung. Inflammation and oxidative stress cause your lungs to develop with alveoli larger than normal and in smaller numbers. This results in the development of bronchopulmonary dysplasia and causes that when growing they have a lower pulmonary capacity, a higher risk of respiratory infections and that present other complications such as pulmonary hypertension.

At birth, premature babies still do not have a completely mature antioxidant system, so when exposed to high concentrations of oxygen, they produce reactive oxygen species that activate different inflammatory pathways. 
 

Our proposal

Although there are several treatments focused on trying to prevent and reduce the effects of bronchopulmonary dysplasia, to date none of them has been shown to significantly reduce the morbidity of these babies.

For this reason what our research group is proposing is to activate prenatally the antioxidant activity in these babies as a possible strategy to reduce lung damage, caused by exposure to high concentrations of oxygen.

The use of a xenobiotic compound derived from vegetables like broccoli, cauliflower, brussels sprouts, can promote chemical-protecting effects.

In the School of Medicine and Health Sciences of Tecnológico de Monterrey, in the Research Group in Human Genetics, to which the doctors Fabiola Castorena and Víctor Lara Díaz belong, both research professors, members of the National System of Researchers, and with the support of students of medical specialties and the Social Service of Medicine, we have worked with an animal model of bronchopulmonary dysplasia in rats, with the aim of seeking new therapeutic targets and treatment strategies to reduce the development of bronchopulmonary dysplasia.

One of the projects that are being developed in this research group is the use of a xenobiotic compound derived from cruciferous vegetables such as broccoli, cauliflower, Brussels sprouts, which can promote chemo-protective effects by regulating antioxidant enzymes and inhibition of proinflammatory pathways. 

This compound was administered to a sample of pregnant rats, whose offspring, at birth, were subjected to periods of high concentrations of oxygen (80%) and hypoxia (10%), similar to those that occur in premature babies, generating structural alterations in the lungs of the offspring, similar to the changes suffered by children with bronchopulmonary dysplasia. 

Thus, studying the histological changes in the lung tissue and the expression of different proteins and genes that participate in the antioxidant system, both in blood and lung tissue of the offspring, we can evaluate in the animal model the effect of prenatal administration of the xenobiotic. 

One of the parameters that are evaluated in the animal models of bronchopulmonary dysplasia is the radial count of the alveoli, which is performed by analyzing the lung tissue in a histological section seen in the microscope, counting the number of alveoli and evaluating the degree of pulmonary development. 

Tecnológico de Monterrey  Histopathology of rat lung on day 13 of life: (A) control group, (B) group exposed to high oxygen concentrations, (C) group treated with xenobiotic and exposed to high oxygen concentrations. Magnification 10x. 

In our study, we found that the alveolar radial count in the offspring of healthy rats was 8, while in the offspring that were exposed to high concentrations of oxygen without receiving the xenobiotic it was 4, and that by administering the xenobiotic in a prenatal and then submit the offspring to high concentrations of oxygen, the count reached 7 (as you can see in the image).

In this study we saw that the prenatal administration of the xenobiotic was innocuous for the pregnant rats, but we managed to improve the activity of the antioxidant system of the offspring and with that diminish the damage produced by the high concentrations of oxygen in the development of their lungs.

It is necessary to perform more evaluations of the effects of the administration of the xenobiotic in the medium and long term in the offspring, but these results are encouraging and give us the opportunity to continue investigating the benefits of its prenatal administration.

Finally, we know that the way to develop an effective treatment that prevents the development of bronchopulmonary dysplasia is long and sinuous, but there is no better reward than to think about the possible benefit that the effort of our entire team can generate.

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The author
Dr. Gabriela Guzmán Navarro is a Surgeon graduated from the School of Medicine of the Tecnológico de Monterrey in 2003. She completed her specialty in Pediatrics also at the Tecnológico de Monterrey. She is currently pursuing a Doctorate in Clinical Sciences at the School. Since 2010 she is a professor at the Medicine and Health Sciences School of Tecnológico de Monterrey and since 2017 she is the Accreditation and Research Coordinator of the Clinical Postgraduate Programs of the School of Medicine and Health Sciences in the North Region. gabriela.guzman@tec.mx

Advisor
Dr. Fabiola Castorena Torres is a Biological Pharmacy Chemist from the Autonomous Metropolitan University, Xochimilco Unit, and obtained her Masters and Doctorate degrees in Science in Toxicology from the Center for Research and Advanced Studies of the Instituto Politécnico Nacional (CINVESTAV-IPN), Zacatenco unit in Mexico City. She is currently a full-time professor-researcher at the School of Medicine and Health Sciences and Coordinator of the Graduate Program in Biomedical Sciences at Tecnológico de Monterrey. She is a member of the National System of Researchers (Level 1). fcastorena@tec.mx

This research project was presented at the “Doctoral Colloquium” during the 49th Research and Development Congress of Técnologico de Monterrey.

By Gabriela Guzmán