Evaluation of cytokines in protective effect of docosahexaenoic acid in experimental achilles tendinopathy rat model induced with type-1 collagenase

ABSTRACT

Background

We aimed to investigate the effectiveness of docosahexaenoic acid (DHA) as a treatment for Achilles tendinopathy (AT) induced with type-I collagenase in rats and compare it with collagen.

Methods

The AT model was induced with type I collagenase, and animals were randomly assigned to groups. Group 1:AT, Group 2: Collagen (7.2 mg/kg/day), Group 3:DHA (300 mg/kg/day), and Group 4:DHA (100 mg/kg/day). Right tendons of Group1 were used as a healthy control (HC). Oral treatments were applied for eight weeks. Serum tumor necrosis factor-alpha(TNF-α), matrix metalloproteinase-13 (MMP-13), and interleukin-1 beta(IL-1β) concentrations were determined by ELISA. Tendon samples were taken for histopathological evaluation and examined immunohistochemically with antibodies specific for Col1A1, TNF-α, MMP-13, IL-1β, and nitric oxide synthase-2(NOS-2). The ultimate tensile force (UTF) yield force(YF) and stiffness were measured by biomechanical assessments.

Results

UTF,YF and stiffness values were increased in all treatment groups compared to the AT control, a significant increase was found in Group 2 (p < 0.05). There was severe degeneration of tendon cells in the AT control. The tendon cells in samples from Groups 2-3 were less degraded, and this was statistically significant (p < 0.05). TNF-α, MMP-13, IL-1β, and NOS-2 expressions were significantly higher in the AT control compared to the HC. In all treatment groups, their concentrations were lower than in the AT control. Serum TNF-α, MMP-13, and IL-1β levels were lower in all treatment groups (Especially in Group3 (p < 0.001)) compared to Group1.

Conclusion

The efficacy of high-dose DHA as a treatment for AT was investigated from biochemical, histopathological, and biomechanical perspectives. The results showed that DHA could be an alternative treatment compound to collagen.

KEYWORDS:

• Docosahexaenoic acid
• collagen
• cytokines
• achilles tendinopathy
• rat

Ethics approval

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

Author contributors

GG, FDM, and KG designed the study. GG, KG, and SYT performed experimental studies. The laboratory studies were performed by GG, FDM, SYT. Histopathological studies were performed by KATK. Biomechanical experiment was conducted by YT. GG, FDM, KG and KATK analyzed the data and interpreted the results. GG, SYT, KG and FDM wrote the paper. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by Ataturk University Scientific Research Projects Unit (project number: THD-2019-7060).