1. Introduction
During last decade, many research groups proved that the oxygen species generate adverse effects [
2,
3] due to the imbalance between the production of ROS (reactive oxygen species) and the body’s biological capacity to neutralize them (i.e., enzymes) [
4,
5]. In the meantime, the evolution of some significant diabetes complications, such as cardiovascular or renal disease, is related to the oxygen species as the primary pathogenic mechanism.
2. Discussion
Almost all of the chronic diseases have been associated with a high quantity of free radicals, or modified signal transductions. In dedicated medical research, two approaches could apply from nutritional interventions point of view: the situation when it is used to prevent a particular disease or, when it is able to alleviate progression, symptoms or complications of the disease. In addition, the considered specific diseases are divided as follows: the group that involves the so-called mitochondrial oxidative stress conditions (cancer and diabetes) and the group that involves the inflammatory or oxidative conditions (atherosclerosis, chronic inflammation, ischemia and reperfusion injury) [
6].
Hyperglycemia in diabetes mellitus is one of the main factors leading to specific structural changes, as protein and lipid oxidation, which are the most common (
Figure 1). For instance, the free radicals induce damage to sulfhydryl groups. As consequence, the proteins are not recognized anymore, resulting in cross-reactions and finally triggering the autoimmune diseases.
In the meantime, abnormal LDL produced by the peroxidation of plasmatic lipids is not identified by liver’s LDL receptors and subsequently, macrophage scavenger receptors take modified LDLs, forming engorged lipid macrophages (LEM), and infiltrate under blood vessel endothelium. It should be also considered that the lipid peroxidation mechanism is governed by the loss of membrane functionality and integrity [
7].
The membrane lipids are influenced by the chain reaction between polyunsaturated fatty acids and ROS. Such chemical processes have as consequence increased cellular membrane permeability as well as an increased calcium influx. The subsequent effect of all these chemical transformations at the membrane level leads to mitochondrial damage. Another aspect to be considered is related to the effects of certain antioxidants whose molecules might change their first functionality in vivo. For instance, melatonin that is a proven antioxidant in vitro [
8] generates circadian rhythm through protein-coupled receptors [
9].
Considering the informational feedback of the oxidative stress (OS) process configured according to the feedback node structure, it was possible to establish which would be the main information necessary to characterize the OS process, namely: OS definition; ROS characteristics (primary – O2, secondary – radicals formation through Fenton and Haber-Weiss processes); ROS behavior against bio-environment; OS action on body; OS quantification and strategies to be applied for OS and ROS. For our case, a complex structural type applies when multiple global feedback could be obtained. The nodes with same feedback can be merged horizontally into another node, leading to an interim feedback. There are two sequences of nodes: first with two nodes and second one with only one node. The feedback embraces one node within a sequence. For instance, the change of the environment (in vitro or in vivo) represents interactions between nodes using environment. Then the direct interaction between two neighboring nodes could be reduced. Taking the advantages of such integrated approach regarding the OS process connected to the diabetes mellitus the thinking models related to the pathogenic mechanisms applied by clinicians could be corrected.
3. Conclusions
In our work, we proved that the approach of the biological processes by help of complex mathematical models allows a correct understanding of pathogenic processes, without applying the simplifying hypothesis or artificial extension of general models.
It has been shown that it is possible to better interpret the oxidative stress using the feedback node model, which present same patterns at lower scale—as cells. The studies that we started could bring a significant difference on approaching the primary and secondary prevention and on other public health issues as well. Such dedicated research could be important for explaining the signaling pathways, which generate chronic diseases (i.e. diabetes).
Author Contributions
The contribution of the authors: Concept, A.P.S. and G.M.; Methodology, F.C., C.S.; Investigation, A.P.S., V.M.; Resources, D.M., E.M.C.; Data curation, E.E.T.; Writing—original draft preparation, A.P.S., E.M.C., E.E.T.; Writing—review and editing, E.E.T.
Funding
This article is based upon work from COST Action NutRedOx-CA16112 supported by COST (European Cooperation in Science and Technology). Also, EET acknowledges the support by a grant of the Romanian National Authority for Scientific Research and Innovation, CCCDI—UEFISCDI, project number 39/2018 COFUND-MANUNET III-HAMELDENT, within PNCDI III.
Conflicts of Interest
The authors declare no conflict of interest.
References
- Goldman, A.W.; Burmeister, Y.; Cesnulevicius, K.; Herbert, M.; Kane, M.; Lescheid, D.; McCaffrey, T.; Schultz, M.; Seilheimer, B.; Smit, A.; et al. Bioregulatory systems medicine: An innovative approach to integrating the science of molecular networks, inflammation, and systems biology with the patient's autoregulatory capacity? Hypothesis Theory 2015, 6, 225. [Google Scholar] [CrossRef] [PubMed]
- Khan, A.N.; Khan, R.A.; Ahmad, M.; Mushtaq, N. Role of antioxidant in oxidative stress and diabetes mellitus. J. Pharmacogn. Phytochem. 2015, 3, 217–220. [Google Scholar]
- Ceriello, A. Diabetes Care. Impaired glucose tolerance and cardiovascular disease: The possible role of post-prandial hyperglycemia. Am. Heart J. 2004, 147, 803–807. [Google Scholar] [CrossRef] [PubMed]
- Sohal, R.S.; Orr, W.C. The redox stress hypothesis of aging. Free Radic. Biol. Med. 2012, 1, 539–555. [Google Scholar] [CrossRef] [PubMed]
- Espinosa-Diez, C.; Miguel, V.; Mennerich, D.; Kietzmann, T.; Sánchez-Pérez, P.; Cadenas, S.; Lamas, S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015, 6, 183–197. [Google Scholar] [CrossRef] [PubMed]
- Nolan, C.J.; Rderman, N.B.; Kahn, S.E.; Pdedersen, O.; Prentki, M. Insulin resistance as a physiological defense against metabolic stress: Implications for the management of subsets of type 2 diabetes. Diabetes 2015, 64, 673–686. [Google Scholar] [CrossRef] [PubMed]
- Stoian, A.P.; Mitrofan, G.; Colceag, F.; Suceveanu, A.I.; Hainarosi, R.; Pituru, S.; Diaconu, C.C.; Timofte, D.; Nitipir, C.; Poiana, C.; et al. Oxidative Stress in Diabetes A model of complex thinking applied in medicine. Rev. Chim. - Bucharest. 2018, 69, 2519–2525. [Google Scholar] [CrossRef]
- Cristache, C.M.; Totu, E.E.; Petre, D.; Buga, R.; Cristache, Gh.; Totu, T. Melatonin and hyaluronic acid mixture as a possible therapeutic agent in dental medicine. Rev. Chim. - Bucharest. 2018, 69, 1996–1999. [Google Scholar] [CrossRef]
- Arsene, A.L.; Mitrea, N.; Cristea, A.; Dragoi, C.M. Evaluation of serum osteocalcin in elderly patients with type-2 diabetes mellitus. Farmacia 2009, 57, 223–228. [Google Scholar]
| Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).