The effect of methylethylpiridinol addition to the therapy on the level of pigment epithelium-derived factor and oxidative status in patients with diabetic nephropathy: randomized controlled open-label clinical study

Sergey Sergeevich Popov; Elena Igorevna Anufrieva; Evgenii Dmitrievich Kryl'skii; Konstantin Konstantinovich Shulgin; Aleksey Nikolaevich Verevkin; Tatyana Nikolaevna Popova; Aleksander Nikolaevich Pashkov

doi:10.1007/s40200-021-00802-6

The effect of methylethylpiridinol addition to the therapy on the level of pigment epithelium-derived factor and oxidative status in patients with diabetic nephropathy: randomized controlled open-label clinical study

J Diabetes Metab Disord. 2021 May 10;20(1):709-717. doi: 10.1007/s40200-021-00802-6. eCollection 2021 Jun.

Authors

Sergey Sergeevich Popov¹, Elena Igorevna Anufrieva¹, Evgenii Dmitrievich Kryl'skii², Konstantin Konstantinovich Shulgin², Aleksey Nikolaevich Verevkin², Tatyana Nikolaevna Popova², Aleksander Nikolaevich Pashkov¹

Affiliations

¹ Voronezh State Medical University named after N.N. Burdenko, Studencheskaya Street 10, 394036 Voronezh, Russia.
² Voronezh State University, Universitetskaya sq. 1, 394018 Voronezh, Russia.

Abstract

Purpose: The diabetic nephropathy is associated with oxidative stress and increases in pigment epithelium-derived factor (PEDF) level in the patient's blood. For the first time, authors investigated the effect of methylethylpiridinol addition to the therapy on oxidative status and pigment epithelium-derived factor concentrations, and examined the relationship between these indicators and clinical markers of pathology development.

Methods: Study design: open label randomized controlled trial study. Authors assessed the effect of methylethylpiridinol addition to the therapy vs basic treatment on antioxidant and NADPH-generating enzymes activity, glutathione's concentration and free radical-induced oxidation's intensity using a spectrophotometric method and iron-induced biochemiluminescence. The pigment epithelium-derived factor concentration in the serum was measured by enzyme-linked immunosorbent assay.

Results: Patients receiving combination therapy with methylethylpiridinol showed a more substantial increase in activity of glutathione peroxidase (Δ = 0.04 ± 0.11, p = 0.002), glutathione transferase (Δ = 0.12 ± 0.08, p < 0.001) and the concentration of reduced glutathione (Δ = 0.30 ± 0.17, p = 0.039). In addition, there was a significant decrease in PEDF level (Δ = -6.4 ± 5.4, p = 0.004). Correlation analysis showed a negative link between Δ postprandial glucose and Δ NADP-isocitrate dehydrogenase (-0.39, p = 0.033), Δ reduced glutathione and Δ postprandial glucose (-0.372, p = 0.043), Δ glutathione transferase and Δ PEDF (-0.37, p = 0.044).

Conclusions: The methylethylpiridinol addition to the therapy had a more potent stimulating effect on the patients' oxidative status in comparison with standard treatment, and reliably decreased pigment epithelium-derived factor level in patients' serum. The observed differences seem to be associated with the antioxidant activity of methylethylpiridinol which contributing to the mitigation of oxidative stress reducing at diabetes mellitus.

Keywords: Antioxidant system; Diabetic nephropathy; Methylethylpiridinol; Oxidative stress; Pigment epithelium-derived factor.