The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study

BACKGROUND: Despite the improvements to enhance skin flap viability, the effects of ischemia-reperfusion (IR), oxidative stress, necrosis, and apoptosis are still challenging. Crocus sativus L. (Saffron) is highly noticeable due to its tissue-protective and antioxidant properties. So, we aimed to investigate its effects on skin flap viability, oxidative stress, apoptosis markers, histopathological changes, and mTOR/p-mTOR expression. MATERIALS AND METHODS: 40 Sprauge-Dawley rats, weighting 200–240 g, were divided into four groups including: (1) Sham (8 × 3 cm skin cut, without elevation); (2) Flap Surgery (8 × 3 cm skin flap with elevation from its bed); (3) Saffron 40 mg/kg + Flap Surgery; and (4) Saffron 80 mg/kg + Flap Surgery. Saffron was administrated orally for 7 days. At day 7, flap necrosis percentage, histopathological changes, malondialdehyde level, Myeloperoxidase and superoxide dismutase activity, Bax, Bcl-2, mTOR, and p-mTOR expression were measured. Protein expressions were controlled by β-Actin. RESULTS: Saffron administration decreased flap necrosis percentage (p < 0.01), which was not dose-dependent. Treatment groups showed significant histological healing signs (Neovascularization, Fibroblast migration, Epithelialization, and Epithelialization thickness), decreased MDA content (p < 0.01), increased SOD (p < 0.01) and decreased MPO activity (p < 0.01). Bax and Bcl-2 expression, decreased and increased respectively in treated groups (p < 0.0001). mTOR and p-mTOR expression were not changed significantly in Saffron treated groups. CONCLUSION: Saffron could increase skin flap viability, alleviate necrosis, decrease oxidative stress and decrease apoptotic cell death, after skin flap surgery, but it acts independent of the mTOR pathway. So, Saffron could potentially be used clinically to enhance skin flap viability. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.https://www.springer.com/00266 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00266-022-03048-6.