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
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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.
KeywordsKefir Scratch assay Histopathology Real-time PCR Burn wound healing
The authors would like to thank the authorities of the Veterinary School, Shiraz University for their kind cooperation. We would also thank the INSF (grant number 96006039) for its kind financial support.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 9.Farina JA, Rosique MJ, Rosique RG (2013) Curbing inflammation in burn patients. Int J Inflam 2013 (2013). http://doi.org/10.1155/2013/715645
- 16.Atalan G, Demirkan I, Yaman H, Cina M (2003) Effect of topical kefir application on open wound healing on in vivo study. Kafkas Univ Vet Fak Dderg 9:43–47Google Scholar
- 21.Muhammad AA, Pauzi NAS, Arulselvan P, Abas F, Fakurazi S (2013) In vitro wound healing potential and identification of bioactive compounds from Moringa oleifera Lam. Biomed Res Int 2013 (2013). https://doi.org/10.1155/2013/974580
- 23.Oryan A, Moshiri A, Meimandiparizi A-H (2011) Effects of sodium-hyaluronate and glucosamine-chondroitin sulfate on remodeling stage of tenotomized superficial digital flexor tendon in rabbits: a clinical, histopathological, ultrastructural, and biomechanical study. Connect Tissue Res 52:329–339CrossRefPubMedGoogle Scholar
- 36.Yüksekdaǧ ZN, Beyath Y, Aslım B (2004) Metabolic activities of Lactobacillus spp. strains isolated from kefir. Mol Nutr Food Res 48:218–220Google Scholar
- 41.Fijan S (2016) Influence of the growth of Pseudomonas aeruginosa in milk fermented by multispecies probiotics and kefir microbiota. J Probiotics Health 3:136Google Scholar
- 43.Yilmaz-Ersan L, Ozcan T, Akpinar-Bayizit A, Sahin S (2016) The antioxidative capacity of kefir produced from goat milk. Int J Chem Eng Appl 7:22Google Scholar
- 49.Oncul O, Yildiz S, Gurer US, Yeniiz E, Qyrdedi T, Top C, Gocer P, Akarsu B, Cevikbas A, Cavuslu S (2007) Effect of the function of polymorphonuclear leukocytes and interleukin-1 beta on wound healing in patients with diabetic foot infections. J Inf Secur 54:250–256Google Scholar
- 50.Hadisaputro S, Djokomoeljanto R, Soesatyo M (2012) The effects of oral plain kefir supplementation on proinflammatory cytokine properties of the hyperglycemia Wistar rats induced by streptozotocin. Acta Med Indones 44:e4Google Scholar
- 64.Nikolic M, López P, Strahinic I, Suárez A, Kojic M, Fernández-García M, Topisirovic L, Golic N, Ruas-Madiedo P (2012) Characterisation of the exopolysaccharide (EPS)-producing lactobacillus paraplantarum BGCG11 and its non-EPS producing derivative strains as potential probiotics. Int J Food Microbiol 158:155–162CrossRefPubMedGoogle Scholar