Effectiveness of Experimental Colitis Therapy with Original Vitamin D3 Rectal Suppositories

Осиков, М. В.; Boyko, M. S.; Федосов, А. А.; Ilyinykh, M. A.

doi:10.21103/article12(1)_oa13

Cited by 4 publications

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“…EC was modeled by two-stage application of a 3% alcohol solution of oxazolone (4-ethoxymethylene-2-phenyl-2-oxazoline-5-oh). At the first stage, cuta neous sensitization was carried out by applying 675 µl/kg to the interscapular area, at the secondrectal injection of 675 µl/kg into the colon to a depth of 8 cm [8].…”

Section: Methodsmentioning

confidence: 99%

“…We have developed original rectal suppositories with vitamin D 3 based on a 10% aqueous solution of vitamin D 3 (Patent 20.05.2019). We have previously demonstrated that vitamin D 3 in the original rectal suppositories in experimental colitis (EC) has a local antioxidant effect by limiting the formation of POL and OMB products; a systemic immunotropic effect by reducing the number of neutrophils, restoring the absorption and HCTreducing activity of neutrophils, reducing the number of lymphocytes, including CD3 + and CD45RA + , reducing the concentration of IgM, IgG, IL-6 and IL-8 [8]. We believe that the systemic immunotropic effects of vitamin D 3 in the composition of the original rectal suppositories in EC are due to its local protective effect in the focus of damage to the colon.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and immunological analysis of the effectiveness of local application of vitamin D<sub>3</sub> in experimental colitis

et al. 2023

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The pathogenesis of inflammatory bowel diseases has not been fully studied, and the therapies used have side effects that limit their use.The purpose of this study is to conduct a clinical and immunological analysis of the effectiveness of vitamin D3 in the original rectal suppositories in experimental colitis (EC).EC was modeled with oxazolone. Original suppositories with vitamin D3 in group 3 and 5-ASA in group 4 were used per rectum. The clinic was evaluated on the Disease activity index scale. The expression of MPO and TNFa, the content of neutrophils, lymphocytes, eosinophils, histiocytes, plasmocytes, fibroblasts, ulcerative defect, tissue damage index were determined in the focus of colon injury. The study was carried out on days 2, 4 and 6.With EC, DAI increases for the entire day, MPO and TNFa increase in the lesion, ulcerative defect isfixed, neutrophil-lymphocytic infiltration increases, and TDI increases. When comparing the morphometric parameters of the alteration zone in EC under the conditions of vitamin D3 use, in contrast to the use of 5-ASA, a decrease in the number of lymphocytes, an increase in fibroblasts was revealed on day 2, a decrease in the number of plasmocytes and an increase in fibroblasts on day 4, an increase in the number of histiocytes and fibroblasts on day 6. The diameter of the ulcerative defect and the TDI index have no significant differences between the compared groups. When comparing the effectiveness of vitamin D3, in contrast to the use of 5-ASA, the MPO content is higher on day 6; the TNFa content is higher on day 4.In EC, the effects of using rectal suppositories with vitamin D3 on clinical signs, the size of the ulcerative defect, the content of MPO and TNFa in the lesion are comparable to the effects of using rectal suppositories with 50 mg of 5-ASA; more pronounced with respect to the dynamics of the cellular composition of the lesion of the colon.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical and immunological analysis of the effectiveness of local application of vitamin D<sub>3</sub> in experimental colitis

et al. 2023

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“…Клинико-морфологическая картина поражения толстой кишки при ОИК соответствует изменениям при ВЗК у человека и позволяет применять оксазолоновую модель колита для изучения патогенеза и апробации эффективности применения новых терапевтических подходов при ВЗК [16,17].…”

Section: обсуждение интерпретация / научная значимостьunclassified

Clinical and Morphological Analysis of Efficacy of Intraperitoneal Ozone Application in Experimental Colitis: Preclinical Randomized Experimental Study

Осиков

Kaygorodtseva

Boyko

et al. 2023

Kuban. nauсh. med. vestnik

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Background. Inflammatory bowel diseases — Crohn’s disease and ulcerative colitis — are chronic gastrointestinal diseases affecting young people of working age. An alternative to basic therapy (5-aminosalicylic acid) for inflammatory bowel disease is the use of ozone, which has anti-inflammatory, immunomodulatory, antibacterial properties and no side effects in therapeutic concentrations. Objective. To perform clinical and morphological analysis of efficacy of intraperitoneal ozone application in experimental colitis.Methods. The study was conducted on 73 male Wistar rats weighing 200-250 g. The animals were divided into four groups by simple randomization. Check studies were performed on the second, fourth and sixth days. Oxazolone-induced colitis was simulated in two stages using a 3%-alcohol oxazolone solution. Ozone-acid mixture was obtained on “UOTA-60-01” unit (“Medozone”, Russia). Rectal suppositories with 5-aminosalicylic acid were prepared on the basis of rectal suppositories “Salofalk”. Clinical status was assessed daily according to the disease activity index (DAI) scale. Morphological evaluation of colon lesion tissue fragments was carried out using a PrimoStar microscope (CarlZeiss, Germany). Colon tissue damage was assessed using tissue damage index (TDI). Statistical analysis was conducted with SPSS Statistics 19 (IBM, USA).Results. Clinical and morphological picture of the large intestine lesion in oxazolone-induced colitis on days 2, 4 and 6 is consistent with the changes typical of inflammatory bowel disease in humans. Daily intraperitoneal insufflation of ozone at a dose of 0.05 mg/kg in oxazolone-induced colitis leads to partial restoration of DAI, reduction in neutrophils, eosinophils, histiocytes, and fibroblasts in the lesion, as well as to a decrease in ulcerous defect diameter and TDI. The effects of intraperitoneal insufflations of ozone in oxazolone-induced colitis as compared to rectal suppositories with 50 mg of 5-aminosalicylic acid every 12 hours were less marked for the DAI index on day 4; for the number of eosinophils, plasma cells, histiocytes — on day 2, 4 and 6; for lymphocytes — on day 6.Conclusion. Clinical and morphological picture of the large intestine lesion in ozone-induced colitis correlates with the changes typical of inflammatory bowel disease in humans. The positive effect of ozone in ozone-induced colitis was driven by its anti-inflammatory properties through the activation of Nrf2 and by its antioxidant properties through the inhibition of Keap1.

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“…Нами разработаны оригиналь- ные ректальные суппозитории с витамином D3 на основе 10%-го водного раствора витамина D3 [13]. Ранее нами продемонстрировано, что витамин D3 в составе оригинальных ректальных суппозиториев при экспериментальном колите (ЭК) обладает системным иммунотропным действием за счет снижения количества нейтрофилов, восстановления поглотительной и НСТ-редуцирующей активности нейтрофилов, снижения количества лимфоцитов, в том числе CD3+ и CD45RA+, снижения концентрации IgM, IgG, IL-6 и IL-8 и антиоксидантного действия за счет снижения содержания в стенке толстой кишки продуктов перекисного окисления липидов и продуктов окислительной модификации белков [14,15,16,17,18]. Полагаем, что системные иммунотропные эффекты витамина D3 в составе оригинальных ректальных суппозиториев при ЭК обусловлены его локальным протекторным действием в очаге повреждения толстой кишки.…”

Section: For Citationunclassified

Comparative analysis of the effectiveness of local application of vitamin D3 and 5-aminosalicylic acid in experimental colitis

Осиков

Boyko

Ushakova

2022

jour

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Introduction. At the moment in the Russian Federation there are no dosage forms with vitamin D3, allowing effective delivery and local effect on the focus of inflammation and the damaged area of the large intestine in inflammatory bowel disease (IBD). Among such dosage forms rectal suppositories are of the greatest interest. The aim of the study was to carry out a comparative analysis of the effectiveness of local administration of vitamin D3 and 5-aminosalicylic acid in experimental colitis. Materials and methods. Experimental colitis (EC) was modeled with oxazolone solution. Suppositories with vitamin D3 and with 5-ASA were applied per rectum every 12 h. Clinical status (DAI), morphometry, colon tissue injury index (TDI), myeloperoxidase (MPO) and TNF-α expression in the lesion were assessed. Results. In EC, DAI is increases, an ulcerative defect is fixed in the lesion of the colon, TDI, neutrophils (NF), lymphocytes (LC), eosinophils (EF), histiocytes (HC), plasma cells (PC), fibroblasts (FB), MPO and TNF-α expression are increased. Vitamin D3 administration reduces DAI, ulcer defect, TDI, MPO and TNF-α expression, the number of NF, EF, LC and PCs, and increases the number of GCs and FBs. Comparison of vitamin D3 and 5-ASA administration revealed comparable efficacy against DAI. Morphometric evaluation of colorectal lesions showed that under the conditions of vitamin D3 administration, in contrast to 5-ASC, less infiltration, edema, signs of healing and repair of ulcerous defects were fixed earlier in EC; MPO expression increased on the 6th day, TNF-α expression on the 4th day. The TDI index on the 4th and 6th days of EC decreased equally under the conditions of vitamin D3 and 5-ASC application. Discussion. The reduction of clinical severity and morphological signs of damage in the large intestine wall at EC against the background of using rectal suppositories with vitamin D3 could be due to pleiotropic effects of vitamin D3. Conclusion. The effect of vitamin D3 in original rectal suppositories is comparable with local application of 5-ASC at EC, it reduces severity of clinical signs, representation of cells involved in tissue destruction, TNF-α and MPO expression in the colon wall and increases representation of cells mediating reparation.

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Effectiveness of Experimental Colitis Therapy with Original Vitamin D3 Rectal Suppositories

Cited by 4 publications

References 0 publications

Clinical and immunological analysis of the effectiveness of local application of vitamin D<sub>3</sub> in experimental colitis

Clinical and immunological analysis of the effectiveness of local application of vitamin D<sub>3</sub> in experimental colitis

Clinical and Morphological Analysis of Efficacy of Intraperitoneal Ozone Application in Experimental Colitis: Preclinical Randomized Experimental Study

Comparative analysis of the effectiveness of local application of vitamin D3 and 5-aminosalicylic acid in experimental colitis

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