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Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats

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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.

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Abbreviations

DZ:

Daidzein

ECM:

Extracellular matrix

HA:

Hyalunoric acid

i.a.:

Intraarticular

IHC:

Immuno-histochemical

IL-1β:

Interleukin 1 beta

iNOS:

Inducable nitric oxide synthase

JNK:

c-Jun N-terminal kinase

KOA:

Knee osteoarthritis

LOD:

the limit of detection

LOQ:

Limit of quantification

MIA:

Monosodium iodoacetate

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

NOS-2:

Nitric oxide syntase-2

NSAIDs:

Non-steroidal anti-inflammatory drugs

OA:

Osteoarthritis

QC:

Quality control

ROS:

Reactive oxygen species

SPSS:

Statistical package for the social sciences

TAS:

Total antioxidant status

TNF-α:

Tumor necrosis factor-alpha

TOS:

Total oxidant status

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Funding

This study was supported by Ataturk University Scientific Research Projects Coordination Unit with project numbers TCD-2018-6146.

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Authors and Affiliations

  1. Department of Physiology, Pamukkale University, Faculty of Medicine, Denizli, Turkey

    Gulsah Gundogdu

  2. Department of Analytical Chemistry, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey

    Fatma Demirkaya Miloglu

  3. Department of Orthopedics and Traumatology, Denizli State Hospital, Denizli, Turkey

    Koksal Gundogdu

  4. Department of Physiology, Ataturk University, Faculty of Medicine, Erzurum, Turkey

    Seymanur Yilmaz Tasci

  5. Department of Medical Laboratory Techniques, Ataturk University, Health Services Vocational College, Erzurum, Turkey

    Mevlut Albayrak

  6. Department of Histology and Embryology, Ataturk University, Faculty of Medicine, Erzurum, Turkey

    Tuba Demirci

  7. Department of Pharmaceutical Technology, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey

    Meltem Cetin

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  1. Gulsah Gundogdu
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  2. Fatma Demirkaya Miloglu
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Contributions

GG, MC, FDM, and KG designed the study. GG, KG, and SYT performed experimental studies. The laboratory studies were performed by GG, FDM, SYT, and MA. Histopathological studies were performed by TD and MA. GG, FDM, MC, and TD analyzed the data and interpreted the results. GG, MC, and FDM wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Gulsah Gundogdu.

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This study was conducted with the approval of the Ataturk University Ethics Committee.

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Gundogdu, G., Demirkaya Miloglu, F., Gundogdu, K. et al. Investigation of the efficacy of daidzein in experimental knee osteoarthritis-induced with monosodium iodoacetate in rats. Clin Rheumatol 39, 2399–2408 (2020). https://doi.org/10.1007/s10067-020-04958-z

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  • DOI: https://doi.org/10.1007/s10067-020-04958-z

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