The role of endogenous intoxication syndrome and the activity of the antioxidant protection system in the survival of generalized parodontitis in nuclear disease patients with toxic hepatitis

Abstract

A prominent place in the structure of narcological disorders is opioid drug abuse. It has been detected that in patients with narcotic dependence, especially those who use substances based on opium, have the frequency and severity of oral cavity diseases significantly increased.

Within patients with a different narcotic experience, predominantly, manifestations of generalized parodontitis (GP) are observed, with inflammatory-destructive processes in parodontum in drug addicts found in 2.5–10 times more frequent than in the population.

The amplification of free radical oxidation of cell membranes with the accumulation of oxidation products is one of the essential links in the complex of mediators of inflammation in the periodontal disease. Intoxication, including narcotic drugs, results in insufficient antioxidant protection, which leads to the diffusion of products of free radical oxidation from soft tissues into bone with induction of collagen fibers destruction. 

Membrane-destructive processes with GP are insufficiently studied.

The aim of the study – to learn the dynamics of indicators of antioxidant defense system in patients with generalized periodontitis with toxic hepatitis under opioid dependence, namely, the study of the level of middle molecules (MM) in serum and MTS, as well as the content of lipid peroxidation (LPO) and activity enzymes of the system of antioxidant protection (AOP) of drug addicted patients with toxic hepatitis at the aggravation of the inflammatory and destructive process in parodontium and comparison of these indices with the group of patients without drugs term dependence.

Materials and Methods.122 patients with generalized periodontitis were examined. Of the 90 patients examined, they had a history of addiction and methadone replacement therapy. 32 patients with chronic generalized periodontitis of moderate severity did not use narcotic substances and formed a control group. Laboratory studies were conducted dynamically – before the course of preventive treatment and after its completion (after 20–24 days).

Statistical processing of the results was performed using Microsoft Excel 2007 (Microsoft® Windows® XP Professional, USA) and Statistic v. 6.0 (StatSoft, USA). Calculated the basic statistical constants (M ± m).

Results and Discussion. As the universal biochemical marker of the syndrome of endogenous intoxication (SEI), the most promising is the study of co-occurrence in blood and other biological fluids of metabolites – SM, with which the occurrence of secondary immunodeficiency (SID) is associated. We conducted a study of the level of SM in the blood serum and in the CSG, as well as the composition of LPO products and the activity of the enzymes of the AOZ system in drug-dependent patients with toxic hepatitis during exacerbation of the inflammatory-destructive process in the periodontium.

The toxic properties of the molecules of the "average mass" in the exacerbation of the inflammatory-destructive process in the periodontium consist in their ability to participate in the development of SID, inhibit the phagocytic activity of leukocytes, induce neurotoxic effects and dramatically increase the permeability of capillary membranes, causing microcirculation disturbances. In patients with exacerbation of the inflammatory-destructive process in the periodontium (control group), the serum level of CM in the serum was doubled (at a rate of (0.52±0.05) g / L, P <0.001), which was (1.06±0.09) g / l. The concentration of SM in the blood serum of drug addicts with toxic hepatitis with exacerbation of HP is twice that of the control group SEI (P <0.001) and 4.17 times higher than the norm (P <0.001), which is (2.17±0.13) g / l. An analysis was made of the dynamics of growth of endogenous intoxication molecules of patients with toxic hepatitis with exacerbation of GP depending on the length of drug addiction. The content of SM in serum with a minimum "length of stay" averaged (1.51 ± 0.15) g / l, which is higher than the value in the control group at 1.39 times (P <0.001). In patients with a period of use of narcotic drugs from 2 to 4 years, the concentration of SM in the blood increased 2.21 times (P <0.001) and amounted to (2.34±0.28) g / l. The highest level of "average mass" molecules was observed in patients with "experience" of drug addiction for more than 4 years, which was (3.17±0.39) g / l, that is, a triple increase (P <0.001). The composition of CM in mixed saliva (non-invasive method) was also analyzed: in drug addicts, there was a more significant increase in SM in the salivary saliva of patients with toxic hepatitis in exacerbation of the inflammatory-destructive process in the periodontium. Thus, the SEI index exceeded the control value by 1.62 times and amounted to (0.55 ± 0.04) g / l (P <0.05), which characterizes the virulence of toxic autoaggression in the examined patients with opioid dependence and the insolvency of organs entering in the functional system of detoxification (liver, immune surveillance systems). The disturbance of lipid peroxidation processes in drug-dependent patients was analyzed depending on the duration of use of opioid preparations. The level of DC in patients with a short "experience" of drug dependence (up to 2 years) was 1.20 times higher than the control value (P <0.001), 1.41 times (P <0.001) over 2–4 years and more than 4 years – 1.59 times (P <0.001). The multiplicity of the increase in the final metabolites of lipid peroxidation also directly depended on the duration of drug dependence. Individual analysis with exacerbation of the inflammatory-destructive process in the periodontium showed multidirectional changes in the activity of enzymes of the AOZ system in the blood, depending on the presence or absence of addiction to narcotic substances. And so, in people with drug addiction against the background of intoxication with narcotic substances, stable changes in the activity of the AOZ system have been revealed: they become stronger with time. Thus, the activity of GP, SOD and CT in whole blood was significantly reduced with an increase in the length of drug dependence in all study groups. Weakness of antioxidant protection is one of the reasons for the progression of the inflammatory process in the periodontium, which gives grounds for the appointment as methods of metabolic correction of drugs with antioxidant activity.

Conclusions. 1. The conducted study showed the presence of metabolic disorders in the exacerbation of the inflammatory and destructive process in periodontia in patients with toxic hepatitis opioid genesis, manifested by the syndrome of endogenous intoxication, characterized by an increase in the concentration of CM in serum and mixed saliva. In drug addicts with HF and toxic hepatitis there is a significant increase in the processes of lipid oxidation - an increase in the content of primary and secondary products (DK and MDA) in serum. At the same time, the most pronounced changes in the indicators of endogenous intoxication syndrome and LPA appeared in patients with a long history of narcotic addiction.

1. Chronic intoxication with narcotic substances in patients with inflammatory-destructive process in periodontia is accompanied by an enzyme imbalance of the AOP system - inhibition of the activity of catalase, superoxide dismutase and glutathione peroxidase. The decrease in AOP activity indicates a deep imbalance in the system of free radical oxidation - antioxidant protection in the direction of activation of the LPO. The accumulation in the body of the products of the LPO (end – MDA and intermediate – DC) and the development of endotoxicosis, leads to stimulation of the monooxygenase system, changes in the reaction of lipid, hormonal, immune status, with the depletion of the antioxidant system. Activation of LPO promotes damage to cellular and subcellular biomembranes of hepatocytes and, accordingly, to the progression of the chronic pathological process in the liver parenchyma.
2. The given data on the participation of free radical oxidation in the genesis of GP indicate the expediency of the use of antioxidants and other bioregulators in the complex therapy of patients with opioid dependence and toxic hepatitis.