Experimental Models of Adenomyosis as the Basis for Developing New Methods in the Treatment of the Disease. Part II. Evaluation of the Effectiveness of Adenomyosis Treatment in Female Wistar Rats

BACKGROUND: This article presents the second stage of the study to evaluate the efficacy and tolerability of new directions of drug therapy for adenomyosis based on an experimental model of the disease. This stage is necessary for the further implementation of innovative therapy regimens into clinical practice. AIM: The aim of this study was to evaluate the efficacy of treating adenomyosis in Wistar rats with the phytoalexin resveratrol, the oxytocin receptor inhibitor atosiban, and the biguanide metformin.

We compared the efficacies of adenomyosis treatment options between female Wistar rats with experimentally tamoxifen-induced adenomyosis treated with atosiban, or resveratrol (trans-form) at different doses, or metformin, or dienogest, and without treatment, and healthy rats given water. Histological examination and a hot plate test were performed.

Out of 83 female Wistar rats, 51 animals with experimentally tamoxifen-induced adenomyosis (main group) were divided into 5 subgroups. The rats of the 1st subgroup were administered atosiban intraperitoneally at a dosage of 0.35 mg/kg/day for 21 days (n = 15). The 2nd subgroup orally received resveratrol at a dosage of 15 mg/kg/day for 30 days (n = 16). The 3rd subgroup orally received resveratrol at a dosage of 45 mg/kg/day for 30 days (n = 8). The 4th subgroup orally received metformin at a dosage of 300 mg/kg/day for 30 days (n = 5). And the 5th subgroup orally received dienogest at a dosage of 1 mg/kg/day for 30 days (n = 7). In addition to the main subgroups, 2 comparison subgroups were created (n = 32): the 6th subgroup included rats with tamoxifen-induced adenomyosis without treatment (n = 24) and the 7th (control) subgroup of healthy rats received water (n = 8). Based on the results of histological examination and the hot plate test, the greatest efficiency in the treatment of adenomyosis was demonstrated by therapy using atosiban and resveratrol at a dosage of 45 mg/kg/day, the data obtained being comparable with the result of using dienogest. Thus, the percentage of adenomyosis cure according to the morphological study was 93% when using atosiban, 88% when using resveratrol at a dosage of 45 mg/kg/day, 86% when using dienogest, 75% when using resveratrol at a dosage of 15 mg/kg/day, and 60% when using metformin. In addition, the parameters in the main group differed from the corresponding data in the subgroup of animals with adenomyosis that did not receive treatment and in the control subgroup (p < 0.05).

Our findings demonstrate using alternative methods in the treatment of adenomyosis. Therapy using atosiban and resveratrol in a higher dosage showed an effect similar to that using dienogest, in both relieving pain and curing adenomyosis, which was confirmed histologically. Perhaps, the use of resveratrol and metformin in combination with therapy registered for the treatment of adenomyosis may potentiate the effect of the drugs, increasing their effectiveness. In turn, intolerance and the presence of side effects when using registered hormone-modulating drugs justify the consideration of these alternative methods as monotherapy. The revealed dose-dependent effect of trans-resveratrol gives grounds to assume the prospects for its use in clinical practice, which requires further research to prescribe treatment to patients with adenomyosis. Full Text About the authors Maria A. Shalina The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Author for correspondence. Email: [email protected] ORCID iD: 0000-0002-5921-3217 SPIN-code: 6673-2660 MD, Cand. Sci. (Medicine) Russian Federation, Saint PetersburgMaria I. Yarmolinskaya The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-6551-4147 SPIN-code: 3686-3605 MD, Dr. Sci. (Medicine), Professor, Professor of the Russian Academy of Sciences, Honored Scientist of the Russian Federation Russian Federation, Saint PetersburgReferences - Patent RUS N 2761754 / 13.12.2021. Yarmolinskaya MI, Shalina MA, Netreba EA, et al Method for creating an experimental model of adenomiosis in wistar rats. (In Russ.) EDN: UHZZVY [cited 2024 Oct 12] Available from: https://patents.s3.yandex.net/RU2761754C1_20211213.pdf - Shalina MA, Yarmolinskaya MI. Animal models of adenomyosis as a basis for the development of new treatment methods. Part I. 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