An increase in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to complications during chronic kidney disease (CKD). This increase essentially derives from the impairment of natural antioxidant systems of the organism. The resulting oxidative stress produces damage to kidney tissue, especially by affecting nephrons and more generally by disrupting the function and structure of the glomerulus and interstitial tubule. This leads to a rapid decline in the condition of the patient and finally renal failure. Possible causes of kidney tissue damage are explored, as are different therapies, especially those related to the administration of antioxidants.ARTICLE HISTORY
The present review summarizes the methods most used in drug search and design, which may help to keep pace with the growing antibiotic resistance among pathogens. The rate of reduction in the effectiveness of many antimicrobial medications, caused by this resistance, is faster than new drug development, thereby creating a worldwide public health threat. Among the scientific community, the urgency of finding new drugs is peaking interest in the use of in silico studies to explore the interaction of compounds with target receptors. With this approach, small molecules (designed or retrieved from data bases) are tested with computer-aided molecular simulation to explore their efficacy. That is, ligand-protein complexes are constructed and evaluated via virtual screening (VS), molecular dynamics (MD), and docking simulations with the data from the physical, chemical and pharmacological properties of such molecules. Additionally, the application of quantitative structure-activity relationship (QSAR), multi-target quantitative structure-activity relationship (mt- QSAR), and multi-tasking quantitative structure-biological effect (mtk-QSBER) can be enhanced by principal component analysis and systematic workflows. These types of studies aid in selecting a group of promising molecules with high potency and selectivity as well as low toxicity, thus making in vitro and in vivo (animal model) testing more efficient. Since knowledge of the receptor topography and receptor-ligand interactions has yielded promising compounds and effective drugs, there is now no doubt that the use of in silico tools can lead to more rapid validation of new potential drugs for preclinical studies and clinical trials.
A worldwide public health problem is chronic kidney disease (CKD) presenting alarming epidemiological data. It currently affects about 10% of the adult population worldwide and has a high mortality rate. It is now known that oxidative stress represents one of the most important mechanisms in its pathophysiology, from the early stages to the terminal phase. Oxidation increases inflammation and reduces the capacity of NO• to relax vascular smooth muscle, in part by decreasing bioavailability of tetrahydrobiopterin (BH4), leading to endothelial dysfunction and high blood pressure, and due to the limited effectiveness of existing treatments, new drugs are needed to prevent and/or treat these mechanisms. The aim of this study was to test apocynin in a 5/6 nephrectomy mouse model of CKD to investigate whether its known antioxidant effect can improve the disease outcome. This effect results from the inhibition of NADPH oxidase and consequently a reduced production of the superoxide anion (). Animals were divided into five groups: sham, 5/6 nephrectomy only, and 5/6 nephrectomy followed by treatment with captopril, losartan or apocynin. The parameters evaluated were blood pressure and markers of oxidative stress () and endothelial function (BH4). There were significantly lower levels of and a greater availability of serum BH4 in the apocynin-treated animals versus the control group and the two other drug treatments. The present findings suggest that apocynin in conjunction with a coadjuvant for modulating blood pressure may be useful for controlling the progression of CRF.
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