Gulsah Gundogdu1, Fatma Demirkaya Miloglu2, Koksal Gundogdu3, Seymanur Yilmaz Tasci4, Mevlut Albayrak5, Tuba Demirci6, Meltem Cetin7. 1. Department of Physiology, Pamukkale University, Faculty of Medicine, Denizli, Turkey. gdemirkaya81@gmail.com. 2. Department of Analytical Chemistry, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey. 3. Department of Orthopedics and Traumatology, Denizli State Hospital, Denizli, Turkey. 4. Department of Physiology, Ataturk University, Faculty of Medicine, Erzurum, Turkey. 5. Department of Medical Laboratory Techniques, Ataturk University, Health Services Vocational College, Erzurum, Turkey. 6. Department of Histology and Embryology, Ataturk University, Faculty of Medicine, Erzurum, Turkey. 7. Department of Pharmaceutical Technology, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
Abstract
BACKGROUND: Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats. METHOD: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 μL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1β, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1β, NOS2, and MMP-13 were analyzed with immunohistochemical methods. RESULTS: HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1β, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1β, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group. CONCLUSION: DZ had anti-inflammatory and antioxidant effects in a rat OA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1β, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.
BACKGROUND:Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats. METHOD: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 μL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1β, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1β, NOS2, and MMP-13 were analyzed with immunohistochemical methods. RESULTS: HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1β, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1β, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group. CONCLUSION:DZ had anti-inflammatory and antioxidant effects in a ratOA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1β, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.
Entities:
Keywords:
Daidzein; Hyaluronic acid; Inflammation; Knee osteoarthritis model
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