Experimental beneficial effect of rosuvastatin on burn wound healing in a rat model

Abstract

BACKGROUND

In addition to their primary lipid-lowering effects, statins also exhibit pleiotropic properties, including anti-inflammatory, immunomodulatory, antimicrobial, antioxidative, and angiogenic effects, all of which promote wound healing. Rosuvastatin, a synthetic hydrophilic statin, has recently been proposed to enhance wound healing by stimulating angiogenesis and accelerating tissue regeneration. Its hydrophilic nature, longer half-life, greater hepatoselectivity, and better efficacy/safety than other statins are believed to contribute to its superior efficacy in wound repair, as suggested by promising preliminary results. However, current data on its use remain limited, necessitating further preclinical and clinical studies to thoroughly investigate this novel treatment option for burns.

AIM

To investigate the effects of rosuvastatin and its mechanism of action on burn wound healing process in an experimental study.

METHODS

Ninety male Wistar albino rats aged 12-16 weeks were randomly assigned to three groups of 30, subjected to burn using specific stainless steel sealer. Burn eschar was removed the following day applying topical rosuvastatin cream (study), Eucerin cream (placebo), normal saline (control), and sterile wound dressing. Each group was divided into three subgroups of ten according to sacrifice day (3^rd, 6^th, 9^th). C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, digital assessment of burn healing, and histopathology were performed.

RESULTS

Using the value on the third day in the control group as the baseline, reductions were measured on the sixth and ninth days. Similarly, reduction values were recorded on the third, sixth, and ninth days in the study group. A statistically significant reduction was observed in the study group compared to the control group, with greater reductions corresponding to later sacrifice days (3^rd, 6^th, and 9^th) in CRP (P < 0.01), TNF-α (P < 0.01), IL-1β (P < 0.01), and IL-6 (P < 0.01) levels and burn size (P < 0.01). Histopathology revealed a statistically significant reduction in inflammatory infiltration, coagulative necrosis, and microhemorrhage (P < 0.01). Conversely, statistically significant increases in neovascularization (P = 0.012) and fibroblastic reactions (P = 0.023) were noted. No adverse effects or deaths were observed.

CONCLUSION

Rosuvastatin reduces inflammation by lowering TNF-α, IL-1β, IL-6, CRP while increasing neo-angiogenesis, fibroblast reactions and microenvironmental protection in burn wounds. These effects promote repair and positively impact burn wound healing.

Keywords: Experimental skin burns; Statins; Rosuvastatin; Burn wound healing; Skin burn treatment; Inflammation; Anti-inflammatory rosuvastatin action

Core Tip: Overall, the data from this original preclinical study confirm that rosuvastatin does not act unidimensionally but simultaneously influences the inflammatory, angiogenic, and reparative phases of burn wound healing. These findings are consistent with data from other statins and expand our understanding of the mechanisms of action of rosuvastatin, highlighting it as a promising therapeutic agent for treating skin burn wounds. Its superiority is attributed to its unique effect profile. The administration of rosuvastatin was safe in this experimental model, with no observed adverse effects. However, further preclinical and clinical studies to assess its safety and efficacy are warranted.