scholarly journals The Effect of Combination Therapy with Melatonin on the Enzymes of Glutathione System and the Level of Transforming Growth Factor- β1 in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease

2021 ◽  
Vol 11 (5) ◽  
pp. 359-369
Author(s):  
S. S. Popov ◽  
E. I. Anufrieva ◽  
E. D. Kryl’skii ◽  
A. N. Verevkin ◽  
K. K. Shulgin

Aim. The aim of the work was to assess the effect of combination therapy with melatonin on the clinical and biochemical parameters of chronic kidney disease (CKD) and type 2 diabetes mellitus (DM), the level of transforming growth factor-β1, lipid profile, activity of the glutathione antioxidant system enzymes and the activity of NADPH-generating enzymes in patients.Materials and methods. The study involved 60 people (19 men and 41 women, average age 65.6 ± 9.3 years) with chronic kidney disease associated with type 2 diabetes. The patients were divided into 2 groups. The first group of patients received basic treatment (n = 30, 8 men and 22 women, mean age 64.1 ± 7.9 years); the second group of participants (n = 30, 11 men and 19 women, mean age 69.0 ± 10.5 years) received 2 mg of melatonin in addition to the basic therapy. The control group consisted of 65 apparently healthy individuals (30 men and 35 women, average age 42.3±17.7 years) with normal indicators of general and biochemical blood tests. In the course of the work, the analysis of clinical and biochemical indicators and lipid profile in blood serum, the level of transforming growth factor-β1 by enzyme immunoassay, the activity of enzymes of the glutathione antioxidant system and NADPH-generating enzymes by the spectrophotometric method were carried out.Results. The use of melatonin additionally with basic treatment compared with standard therapy led to a decrease in proteinuria (p=0.010), hyperglycemia (p=0.019), urea concentration (p=0.043), glycated hemoglobin (p=0.045) and transforming growth factor-β1 levels (p=0.020) in patients with CKD. In addition, the use of this drug led to a changing of the lipid profile, and the activity of glutathione antioxidant system enzymes and NADPH-generating enzymes.Conclusion. The differences observed during the study were apparently caused by the action of melatonin, which has nephroprotective and hypoglycemic properties, the ability to neutralize reactive oxygen species and activate the antioxidant system functioning. 

HORMONES ◽  
2011 ◽  
Vol 10 (2) ◽  
pp. 125-130 ◽  
Author(s):  
Anna-Maria Touvra ◽  
Konstantinos Volaklis ◽  
Apostolos Spassis ◽  
Christos Zois ◽  
Helen Douda ◽  
...  

2021 ◽  
Vol 6 (1) ◽  
pp. 72-77
Author(s):  
R. F. Yeromenko ◽  
◽  
O. N. Litvinova ◽  
V. V. Kozar ◽  
A. L. Litvinenko ◽  
...  

The purpose of the study was to examine the levels of transforming growth factor-β1 in the serum of patients with coronary heart disease in combination with type 2 diabetes and without it. Material and methods. We conducted a survey of 65 patients (25 men, 40 women) aged from 36 to 69 years (mean age was (59±3.5) years). All patients were diagnosed with coronary heart disease in the form of stable angina pectoris I-II functional classes. The group of examined patients included 33 patients with concomitant type 2 diabetes mellitus (mild form was in 15 people; moderate was in 18 people) and 32 patients without diabetes mellitus. The scope of the survey covered the generally accepted methods of clinical, laboratory and instrumental examination. The group of patients with coronary heart disease with type 2 diabetes had 14 (43%) men and 19 (57%) women (mean age was (62±2.6) years. Heart failure of stage I-II A (I-II functional classes) was diagnosed in 22 (68%) patients. The duration of coronary heart disease was from 3 to 15 years, the duration of type 2 diabetes lasted from 3 to 14. We detected hypertension in 19 (57%) patients, it was within 1-2 degrees (according to the criteria of the Ukrainian Association of Cardiologists, 2008). In the group of patients with coronary heart disease without diabetes there were 11 men (34%), 21 women (66%) (mean age was (57.0±2.4) years). Hypertension within 1-2 degrees was detected in 15 (46%) patients. Heart failure of I-II A stages (I-II functional classes) was diagnosed in 15 (46%) patients. The control group consisted of 15 practically healthy individuals who were representative by sex and age of patients from the study group and who did not have diseases of the cardiovascular system and endocrinopathies. The level of transforming growth factor-β1 in the blood serum was determined using sets of standard test systems "TGF-β1 ELISA" produced by company "DRG Instruments" (Germany). The level of native transforming growth factor-β1 in the serum was determined by solid-phase enzyme-linked immunosorbent assay. Results and discussion. Groups of patients with coronary heart disease with type 2 diabetes and without it could be compared by age, sex, duration and severity of coronary heart disease, the frequency of concomitant hypertension. At the same time, among patients with coronary heart disease with type 2 diabetes there was a higher frequency of heart failure. The results showed that probable increase in serum transforming growth factor-β1 levels in patients with coronary heart disease was more pronounced when combining coronary heart disease with type 2 diabetes. There was a significant increase in serum of transforming growth factor -β1 levels in patients with coronary heart disease both with type 2 diabetes and without it with a longer course of coronary heart disease and were severer, in patients with coronary heart disease with type 2 diabetes was with a longer course of diabetes. Analysis of the nature of changes in the levels of transforming growth factor-β1 in the serum of the examined patients with coronary heart disease with type 2 diabetes and without it, depending on gender, did not reveal any significant differences. The results of the study also indicated that in patients with coronary heart disease with type 2 diabetes and without it for all duration of coronary heart disease, the levels of this indicator in the serum were probably (p <0.05) higher than those in the control group. However, in patients with a significant duration of coronary heart disease (5-10 years and over 10 years) serum levels of transforming growth factor-β1 were probably (p <0.05) higher than in patients with a duration of coronary heart disease less than 5 years, and in the presence of and in the absence of type 2 diabetes. At the same time, for all periods of coronary heart disease, the levels of transforming growth factor-β1 in patients with type 2 diabetes were probably higher than in patients without diabetes. Conclusion. A probable increase in the levels of transforming growth factor -β1 in the serum of patients with coronary heart disease, which was more pronounced when combining coronary heart disease with type 2 diabetes. There was a significant increase in the levels of transforming growth factor-β1 in the serum of patients with coronary heart disease both with type 2 diabetes and without it with a longer course of coronary heart disease and its severe degree, in patients with coronary heart disease with type 2 diabetes especially with a longer course of diabetes. In order to increase the informativeness of assessing the risk of cardiovascular complications and the nature of coronary heart disease in patients with type 2 diabetes, the survey should include determination of serum levels of potent profibrogenic factor like transforming growth factor-β1


2021 ◽  
Vol 52 (8) ◽  
pp. 653-665
Author(s):  
Aglaia Chalkia ◽  
Harikleia Gakiopoulou ◽  
Irini Theohari ◽  
Periklis G. Foukas ◽  
Dimitrios Vassilopoulos ◽  
...  

<b><i>Introduction:</i></b> Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). <b><i>Methods:</i></b> We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3), and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN, and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. <b><i>Results:</i></b> TGF-β1 expression correlated positively with segmental glomerulosclerosis (<i>p</i><b></b>= 0.025) and creatinine level at diagnosis (<i>p</i> = 0.002), while pSmad3 expression with interstitial inflammation (<i>p</i> = 0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (<i>p</i> = 0.011), intense interstitial inflammation (<i>p</i> = 0.029), and lower serum complement (C) 3 (<i>p</i> = 0.028) and C4 (<i>p</i> = 0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (<i>p</i> = 0.045) and in podocytes of nonproliferative GN (<i>p</i> = 0.005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (hazard ratio = 6.078; 95% confidence interval: 1.168–31.627; <i>p</i> = 0.032) was emerged as independent predictor for CKD. <b><i>Discussion/Conclusion:</i></b> TGF-β1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.


2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Hodaka Yamada ◽  
Makoto Kuro-o ◽  
Shunsuke Funazaki ◽  
San-e Ishikawa ◽  
Masafumi Kakei ◽  
...  

Renal function decline is associated with progressive type 2 diabetes mellitus, which causes mineral and bone disorders. In the present study, we defined the ratio of urinary phosphate excretion (mg/day) to serum fibroblast growth factor 23 as the nephron index. We examined changes in the nephron index in type 2 diabetes patients with early stage chronic kidney disease (stages 1–3), enrolling 15 patients and retrospectively analysing the follow-up data. After follow-up at 5.4 years, we observed no significant changes in the estimated glomerular filtration rate; the nephron index, however, was significantly reduced between the baseline and the follow-up. We propose that the nephron index may be potentially useful as a biomarker for monitoring the decline of renal function in the early stages of diabetic chronic kidney disease patients.


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