Experimental malnutrition: A systematic review

The protein-energy malnutrition (PEM) is an important public health problem. This study aimed to perform a systematic review of articles published in English and Portuguese in the last decade, aimed at research on experimental malnutrition. It was selected studies published from January 2006 to August 2015. The descriptors used were from “modelo de desnutrição” and “model of malnutrition”. The databases consulted were Scielo, PubMed, Lilacs and Cochrane Library. In 17 articles, positive and negative outcomes of malnutrition were searched in different databases. Among these, 8 articles researched the correlation of malnutrition with immune system or gastrointestinal system and 5 articles analyzed the hematopoietic system and the skeletal system. Only 1 paper analyzed the cardiovascular system, 1 analyzed the cutaneous system and 2 the malnutrition itself. Experimental malnutrition articles need to standardize models for malnutrition in more details throughout his writings. Furthermore, it was observed that the studies about malnutrition did not search the relation between surgical stress and malnutrition.


Introduction
The protein-energy malnutrition (PEM) is a major public health problem that affects millions of people worldwide and can be described as a form of malnutrition where there is inadequate calorie or protein intake. Extreme cases induces in the individual a series of biochemical and organic changes, causing changes in bodily function, and is associated with worsening of the diseases [1].
The PEM has been a statistically significant problem in surgical patients, affecting 22-58% of cases, and is related to higher hospital costs, longer hospitalization, predisposing to a variety of complications, higher incidence of infections and mortality [2]. Clinically, the PEM can be classified into marasmus (deficiency in calorie intake), kwashiorkor (protein malnutrition predominant) or a combination of both, marasmus-kwashiorkor [3].
In this context, laboratory animals have been used increasingly to assess the effects of malnutrition degrees variables in susceptibility to infections and also in the various parameters of the immune response, as well as in several pathologies related to malnutrition [1]. The big advantage of using animal models is to allow highly controlled evaluation of each nutritional parameter, considering that is not possible in the case of human populations.
In this scenario, the present study was to conduct a systematic review of articles published in English and Portuguese in the last decade, aimed at research on experimental malnutrition.

Materials and method
The included studies were about experimental malnutrition, published from January 2006 until August 2015. Keywords used were "modelo de desnutrição" and "model of malnutrition". Data bases consulted were Scielo, Pubmed, Lilacs and Cochrane Library. It was established the following criteria for inclusion: studies which used

Discussion
On the analysis of studies of this review, it can be seen that the experimental malnutrition has become an important area for the better understanding of the pathophysiology of malnutrition. In this regard, several systems have been the subject of research around the world. In China, for example, a study investigated radiographic abnormalities [4]. However, it was the gastrointestinal and immune systems were revealed as the main targets of interest of the scientific community nowadays.
It is noteworthy that the most prevalent cause of immunodeficiency worldwide is severe malnutrition which affects up to 50% of the population in poor countries. The immunological changes resulting from malnutrition can affect both the innate immunity in respect of specific. It has been noted that the availability of components of the complement system and phagocytic function are compromised in malnutrition and this hampers the elimination of pathogens. Both the C3 level, which is the main component opsonic, and the ability of phagocytes to internalize and destroy pathogens, appear reduced in states of desnutrição [5]. Such statements have been exemplified in the studies that correlate immune system with malnutrition, where the main roads studied were the NF-κB and inhibiting macrophages by interleukin 10 [6-10].
The other most studied system was the gastrointestinal which is markedly affected by the effects of PEM. In general, PEM affects the gastrointestinal tract causing atrophy of the gastric and intestinal mucosa. In the stomach causes hyperplasia, ulcerated lesions, decreased hydrochloric acid, weakening of gastric barrier to bacteria. In the intestines, there is a reduction of crypts, villi and intestinal microvilli, size of enterocytes, decreased intestinal transit may generally to constipation, and due to attenuation of the immune system, it is usual to observe infections and diarreia [11][12][13][14][15]. Interestingly, other studies, malnutrition was not significantly contribute to the worsening of the intestinal barrier in rotavirus infection, or to decrease the potency of the vaccine against this pathogen [13,16]. The loss of thymocytes was identified in a study, this loss, as well as changes in the intestinal mucosa, they can be ameliorated by supplementation with probiotic fermented milk [17].
In addition to the immune, and gastrointestinal systems have also been studied bone and hematopoietic system, the main findings loss of bone cells leading to defects like deficient hematopoiesis, lacking blood cells. It has been evidenced histological and radiographic abnormalities in mouse models with Kashin-Beck disease induced malnutrition [4]. Treatment with parathyroid hormone is effective in reversing the deleterious effects of malnutrition long term [18]. In malnutrition, anemia is caused by deficient erythropoiesis as the serum iron and erythropoietin in malnutrition do not change [19].
Although all the selected works have placed on your method data related to diet adopted by the animals, few jobs that have adopted an explicit model of induction to malnutrition, which could easily be replicated by other authors. This was the case of the work of Pantoja et al. [20] and Leite et al. [3], both studies could be considered innovative. At first, it was used as food biscuit flour, "polvilho", (totally devoid of protein) in Wistar rats diet to check for changes that malnutrition can result in blood gas analysis. Leite et al. used two models to arrive malnutrition: marasmus model which was to halve the mice food portions and the gelatin model, which would correspond to normal protein diet associated with low protein quality [20,3]. In the skin, malnutrition causes loss of collagen with less dermal thickness and negatively influences the tropism cutaneous [3]. As the cardiovascular system, malnutrition induces endothelial dysfunction, an increase of superoxide and nitric oxide in addition to the increased blood pressure [21].
Merino-Sanjuan et al. [22] used the pharmacokinetic study for malnutrition in animal model. Conclusion was the body weight of animals can be predicted at a given time takin in account the diet followed in the experimental period.
It is believed that, as the main characteristics for a model malnutrition, are practicality, the induction time and the adequacy of the animal studied. The evaluated articles, however, can see a significant discrepancy between the induction time in the researched articles, which would justify closer future studies to validate the best induction time for certain species.

Conclusion
It was observed that it is necessary that the experimental malnutrition articles standardize models for induction malnutrition in more detail in the course of his writings, so that other authors may have access to these techniques and can replicate them. In addition, it was noted that the scientific arsenal is lacking in research correlating malnutrition to one of its main causes today: surgical stress.