Role of inflammation and oxidative stress in tissue damage associated with cystic fibrosis: CAPE as a future therapeutic strategy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

Pancreatic Insufficiency in a Child with p.Gly542* and c.2657+5G>A Heterozygote CFTR: A Case Report.

Cystic fibrosis is a monogenic and autosomal recessive disease. It is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene responsible for encoding the CFTR protein. Involvement of the gastrointestinal and respiratory systems is the main clinical manifestation. In this case, we report a heterozygous CFTR patient harboring class I (p.Gly542*) and class V (c.2657+5G>A) mutations. The importance of this case report lies in the clinical features because the patient, aged 3 years, presented with early exocrine pancreatic insufficiency, which can be considered atypical, as most individuals with this genotype are pancreatic sufficient or develop pancreatic insufficiency later in life. This report aims at presenting the tests requested that contributed to the patient's diagnosis, as well as at understanding the association between these mutations and their phenotypic presentation. Interpretation of the genotype-phenotype relationship represents a challenge, as genetic analysis alone is not sufficient to clearly predict severity of the disease. This is because the significant phenotypic heterogeneity existing among patients with the same genotype may exert socioeconomic and sociocultural influences, or by the action of CFTR modifiers, such as environmental and modifying genes, which can alter the protein's function and exert an impact on the individual's phenotype.

Hyperinflammation and airway surface liquid dehydration in cystic fibrosis: purinergic system as therapeutic target.

OBJECTIVE AND DESIGN: The exacerbate inflammatory response contributes to the progressive loss of lung function in cystic fibrosis (CF), a genetic disease that affects the osmotic balance of mucus and mucociliary clearance, resulting in a microenvironment that favors infection and inflammation. The purinergic system, an extracellular signaling pathway characterized by nucleotides, enzymes and receptors, may have a protective role in the disease, through its action in airway surface liquid (ASL) and anti-inflammatory response. MATERIALS AND METHODS: To make up this review, studies covering topics of CF, inflammation, ASL and purinergic system were selected from the main medical databases, such as Pubmed and ScienceDirect. CONCLUSION: We propose several ways to modulate the purinergic system as a potential therapy for CF, like inhibition of P2X7, activation of P2Y2, A2A and A2B receptors and blocking of adenosine deaminase. Among them, we postulate that the most suitable strategy is to block the action of adenosine deaminase, which culminates in the increase of Ado levels that presents anti-inflammatory actions and improves mucociliary clearance. Furthermore, it is possible to maintain the physiological levels of ATP to control the hydration of ASL. These therapies could correct the main mechanisms that contribute to the progression of CF.