The effects of combination therapy with finasteride and all-trans retinoic acid on skin flap survival: a rat model

نویسندگان

1 Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

2 Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Department of Community Medicine, School of Medicine, Food Health Research Center, Hormozgan University of Medical Sciences

doi
10.22034/ijd.2024.404005.1725
چکیده

Background: Skin flap viability is a major concern in surgical procedures due to the detrimental effects of ischemia-reperfusion, oxidative stress, and inflammation, which can lead to necrosis. Finasteride and all-trans retinoic acid (ATRA) have potential antioxidant and anti-inflammatory characteristics. The aim of this study is to investigate the effects of their combination therapy on survival rates, oxidative stress markers, and histopathological alterations in a rat model of skin flap.Methods: Male Wistar rats were divided into five groups: Sham, Control, Finasteride, ATRA, and Finasteride & ATRA. Finasteride (5 mg/kg) was administered orally, while ATRA (1%) was applied topically. On the seventh day post-flap surgery, tissue samples were collected. The necrotic area of the flaps, levels of malondialdehyde (MDA), myeloperoxidase (MPO) activity, and superoxide dismutase (SOD) activity were measured. Histopathological evaluations for fibroblast migration, granulation tissue formation, inflammation, and necrosis were conducted using hematoxylin and eosin (H&E) staining.Results: Combination therapy with finasteride & ATRA significantly reduced the percentage of flap necrosis, levels of MDA, MPO activity, as well as microscopic necrosis, and inflammation (P < 0.05). Additionally, this combination therapy enhanced SOD activity, granulation tissue formation, and fibroblast migration (P < 0.05).Conclusion: Our findings demonstrate that combination therapy with finasteride and ATRA has potential benefits for improving survival rates and mitigating histopathological alterations in skin flap tissue. Additionally, this approach may effectively reduce oxidative stress and enhance the antioxidant defense mechanisms of flap tissue. However, further investigation is essential to elucidate the underlying molecular mechanisms and potential clinical applications of this therapeutic strategy.