Kefir Accelerates Burn Wound Healing Through Inducing Fibroblast Cell Migration In Vitro and Modulating the Expression of IL-1ß, TGF-ß1, and bFGF Genes In Vivo

Abstract

Kefir is a natural probiotic compound with a long history of health benefits which can improve wound healing. This study investigated the regeneration potential of kefir in vitro scratch assay and in vivo burn wound in rat model. Cytotoxicity of different concentrations of kefir was evaluated by colorimetric methylthiazoltetrazolium assay. A scratch wound experiment was performed to investigate the ability of kefir in reducing the gap of wounds in a dose-dependent manner, in vitro. The standardized kefir was incorporated into silver sulfadiazine (SSD) and applied on burn wounds in vivo, and was compared with the SSD and negative control groups after 7, 14, and 28 days of treatment. The wound sites were then removed for histopathological and morphometric analyses, assessment of interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), dry weight, and hydroxyproline contents. Kefir enhanced proliferation and migration of human dermal fibroblast (HDF) cells and 12.50, 6.25, and 3.12 μL/mL concentrations showed better effects on the scratch assay. Kefir resulted in reduction of IL-1β and TGF-β1 expression at day 7 compared to the negative control. Kefir also reduced the expression of IL-1β at days 14 and 28 and stimulated bFGF at day 28. It significantly improved the dry matter and hydroxyproline contents in the burn wounds. Kefir also resulted in enhanced angiogenesis and elevated migration and proliferation of fibroblasts and improved fibrous connective tissue formation in the wound area. The morphometric results indicated significant global contraction values in the kefir-treated wounds compared to other groups. Taken together, the findings suggest that kefir has considerable ability to accelerate healing of the burn wounds. Therefore, kefir may be a possible option to improve the outcomes of severe burns.

Keywords: Burn wound healing; Histopathology; Kefir; Real-time PCR; Scratch assay.