&lt;p&gt;Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress&lt;/p&gt;

Lin, Jinti; Jia, Chang; Wang, Yongli; Jiang, Shanghong; Jia, Zhen‐Yu; Chen, Nan; Sheng, Shimin; Li, Shihen; Jiang, Liangfu; Xu, Huazi; Zhou, Kailiang; Chen, Yijie

doi:10.2147/dddt.s195479

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…The malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) assays (Nanjing, China) were performed to determine the oxidative stress levels in ischemic flaps (Lin et al, 2019). Tissue samples were obtained from Area II flaps as above ( n = 6 per group), 7 days after the operation.…”

Section: Methodsmentioning

confidence: 99%

Apigenin enhances viability of random skin flaps by activating autophagy

Zhu

Chen

Xiang

et al. 2021

Phytotherapy Research

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Funding informationScience and Technology Department of Zhejiang Province, Grant/Award Number : LGF20H060013 Random skin flap is widely used in plastic surgery. However, flap necrosis caused by ischemia-reperfusion injury limits its clinical applications. Apigenin, a naturally occurring flavonoid mainly derived from plants, facilitates flap survival. In this study, we explored the effects of apigenin on flap survival and the underlying mechanisms. A total of 54 mice having a dorsal random flap model were randomly divided into control, apigenin, and apigenin +3-methyladenine groups. These groups were treated with dimethyl sulfoxide solution, apigenin, and apigenin +3-methyladenine, respectively. The animals were then euthanized to assess angiogenesis, apoptosis, oxidative stress, and autophagy levels through histological and protein analyses. Apigenin promotes survival of the skin flap area and reduces tissue edema. In addition, apigenin enhanced angiogenesis, attenuated apoptosis, alleviated oxidative stress, and activated autophagy. Interestingly, 3-methyladenine reversed the effects of apigenin on flap survival, angiogenesis, apoptosis, and oxidative stress through inhibition of autophagy. The findings of this study show that apigenin promotes angiogenesis, inhibits cell apoptosis, and lowers oxidative stress by mediating autophagy, thus the improving survival rate of random skin flaps.

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Section: Methodsmentioning

confidence: 99%

Apigenin enhances viability of random skin flaps by activating autophagy

Zhu

Chen

Xiang

et al. 2021

Phytotherapy Research

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“…Two percent (w/v) of pentobarbital sodium (40 mg/kg) was injected intraperitoneally to rats for anesthesia. The random-pattern skin flap was established in the central dorsum according to the modified McFarlane flap model performed in published studies 32,33 . In brief, after shaving hair and disinfecting, a caudal skin flap (3 cm × 9 cm) was cut and separated from subcutaneous deep fascia on the rat back.…”

Section: Methodsmentioning

confidence: 99%

FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival

et al. 2019

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Random-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21's therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use.

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“…Flap necrosis primarily occurs due to ischaemiareperfusion injury (IRI) caused by insufficient blood supply to the distal flap and postischaemic reperfusion, which leads to the production of reactive oxygen species (ROS). Simultaneously, the strong local inflammatory response that occurs after the flap operation also stimulates cell damage and necrosis in the flap tissue [5][6][7]. Therefore, previous studies have focused on the identification of specific drugs to inhibit oxidative stress, cell death, and inflammatory responses that promote tissue survival [8,9].…”

Section: Introductionmentioning

confidence: 99%

Liraglutide, a TFEB‐Mediated Autophagy Agonist, Promotes the Viability of Random‐Pattern Skin Flaps

Zhu

Lou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Random skin flaps are commonly used in reconstruction surgery. However, distal necrosis of the skin flap remains a difficult problem in plastic surgery. Many studies have shown that activation of autophagy is an important means of maintaining cell homeostasis and can improve the survival rate of flaps. In the current study, we investigated whether liraglutide can promote the survival of random flaps by stimulating autophagy. Our results show that liraglutide can significantly improve flap viability, increase blood flow, and reduce tissue oedema. In addition, we demonstrated that liraglutide can stimulate angiogenesis and reduce pyroptosis and oxidative stress. Through immunohistochemistry analysis and Western blotting, we verified that liraglutide can enhance autophagy, while the 3-methylladenine- (3MA-) mediated inhibition of autophagy enhancement can significantly reduce the benefits of liraglutide described above. Mechanistically, we showed that the ability of liraglutide to enhance autophagy is mediated by the activation of transcription factor EB (TFEB) and its subsequent entry into the nucleus to activate autophagy genes, a phenomenon that may result from AMPK-MCOLN1-calcineurin signalling pathway activation. Taken together, our results show that liraglutide is an effective drug that can significantly improve the survival rate of random flaps by enhancing autophagy, inhibiting oxidative stress in tissues, reducing pyroptosis, and promoting angiogenesis, which may be due to the activation of TFEB via the AMPK-MCOLN1-calcineurin signalling pathway.

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<p>Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress</p>

Cited by 12 publications

References 38 publications

Apigenin enhances viability of random skin flaps by activating autophagy

Apigenin enhances viability of random skin flaps by activating autophagy

FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival

Liraglutide, a TFEB‐Mediated Autophagy Agonist, Promotes the Viability of Random‐Pattern Skin Flaps

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