Efficacy of Quercetin on rat eyelid wound healing, a randomized, sham-controlled double-blind study

doi:10.21203/rs.3.rs-4155053/v1

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Efficacy of Quercetin on rat eyelid wound healing, a randomized, sham-controlled double-blind study

https://doi.org/10.21203/rs.3.rs-4155053/v1

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Introduction:

Although quercetin has been found to be useful in the treatment of pressure wounds due to its ability to reduce oxygen radicals, its effect on healing wounds on the eyelids is not clear.

Objective

To investigate the effect of quercetin on eyelid wound healing.

Method and Materials:

Forty male Wistar Albino Rats weighing 250–300 grams were used. Four groups were created. Control Group (n = 10), Sham Group (n = 10), Incision Wound Group (n = 10), and Suture + Quercetin Group (n = 10). Full-thickness skin excision was performed through a 3–5 mm incision in the superior palpebrae to create a wound. On the 3rd day and (n = 5) on the 7th day, they were sacrificed, and blood samples were taken by cardiac puncture for biochemical measurement and tissue samples for histopathological examination from the palpebrae.

Results

Inflammatory cells in the Quercetin Group were significantly lower in 3. Day (p < 0.05). Blood levels of IL-1 and TNF-alfa were significantly lower in the Quercetin Group (p < 0.05) when compared with other groups. The Quercetin Group is as influential as the sham group at 3. Day for collagen formation and hydroxyproline value is significantly higher. Total oxidant status levels were lower in the Quercetin group than in the Sham group (p = 0.005).

Conclusions

Quercetin was found to be anti-inflammatory and antioxidant, and these properties can lead to decrease in wound healing time. Also, Quercetin healed wounds and scavenged free radicals effectively.

dermatologic surgery

eyelid surgery

quercetin

wound healing

This is the first research in the literature to focus on palpebra of rats in term of antioxidant properties of quercetin and it was found to be anti-inflammatory and antioxidant, and these properties can lead to decrease wound healing time.

Reactive oxygen species (ROS) play an essential role in the normal wound healing process. Thus, it is necessary to maintain an ideal balance between low and high ROS levels. New treatments focus on antioxidant products that regulate this balance. As well as facilitating the adhesion of leukocytes to wounds and the chemotaxis of proinflammatory factors into wounds, ROS have also been shown to inhibit keratinocyte migration and re-epithelialization. (1) (2)

It is pertinent to ask whether a model that simulates impaired wound healing can replicate all the complexities associated with the healing process of a human wound. (1–4) To study the healing process of wounds, pathological problems that are typically chronic in humans must be carefully simulated in animals. This will enable them to survive for an extended period.

The healing process consists of four overlapping stages: proliferation, wound remodeling, hemostasis, and inflammation. There are, however, many chronic wounds, including pressure ulcers, arterial, and venous. They are defined by prolonged inflammation and, as a result, protease, reactive oxygen species (ROS), and high levels of proinflammatory cytokines. During the recovery process for chronic wounds, stalls can occur at any point. This is from the time of their initial presentation to the time when they are close to healing. (6) (7) The presence of macrophages at higher levels than average in chronic wounds resulted in increased inflammatory cytokines such as tumor necrosis factor-alpha (TNF). (8). As part of remodeling, fibroblast proliferation, and migration, this factor contributes to wound healing when released under controlled conditions. ROS production and extracellular matrix degradation are two ways TNF induces chronicity when it is upregulated. (9–12)

In this study, identifying compounds with antioxidant properties that have been tested for wound healing and reviewing the evidence supporting their effectiveness is a major objective. Gonathi et al. found that a collagen matrix containing Quercetin had a greater ability to heal wounds and scavenge free radicals than a collagen matrix at Day 7 compared with collagen-treated wounds. Quercetin also resulted in a higher percentage of wound contraction in animals treated with the drug. (20 ± 1.77) (13). An animal model was used by Yin et al. to investigate the novel effects of the topical application of Quercetin on pressure ulcers. According to the study, Quercetin successfully reduced immune cell infiltration and proinflammatory activity in wounds. The wounds treated with Quercetin had nearly closed by Day 14, whereas the wounds in the control group had healed only 80 percent by that day. Thus, it has been determined that Quercetin may be an effective treatment for pressure ulcers. (14) This study will examine the effects of Quercetin on wound healing in the eyelid, an area that had never been examined prior to this study and has thin skin. At topical application, Quercetin has been shown to improve cutaneous wound healing in rats; however, due to its hydrophobic nature and limited skin penetration, it is not an ideal treatment for cutaneous wounds. Therefore, this study was designed to determine whether oral Quercetin could promote wound healing.

Various foods contain flavonoids, like apples, green leafy vegetables, tea, strawberries, and onions. Quercetin can be found naturally in many fruits, vegetables, and plants. There was a down-regulation of collagen III and smooth muscle actin by Quercetin in human keratoconus corneal stromal cells, two key markers of fibrosis in the cornea. Furthermore, we found that Quercetin inhibited transforming growth factor-b2 (TGF-b2) expression in the presence and absence of excess lactate. TGF-b signaling has been identified as one of the key players in corneal fibrosis, and several strategies have been proposed to inhibit its activity. It may be possible to inhibit corneal scarring by regulating the expression of TGF-b with Quercetin. (15)

This study involved 40 male Wistar Albino Rats weighing between 250 and 300 grams.

Anesthesia for experiments is prepared with an intramuscularly given (13 mg/kg) dose of Xylazine HCL (Rompun 2%, 23.32 mg/ml, 50 ml Fl. Bayer) and 87 mg/kg dose of Ketamine Hydrochloride (Alfamine 10%). In this study, the right eye was cleaned with Povidone iodine following regional techniques, after the right eye palpebra superior hairs were shaved with a razor blade, taking care not to injure. Control group (n = 10): On day 0, the cases were sacrificed with a high-dose anesthetic, and blood samples were taken by cardiac puncture.

Sham Group (n = 10): The rats in this group performed a full-thickness skin excision with a 3–5 mm incision in the palpebra superior of the right eye under general anesthesia and sterile conditions on day 0, and a wound was created. The wound was closed by applying simple separate sutures with 7 − 0 Nylon sutures. In this group (n = 5), on the 3rd day and (n = 5) on the 7th day, they were sacrificed with a high-dose anesthetic, and blood samples were taken by cardiac puncture for biochemical measurement, and tissue samples for histopathological examination from the palpebrae. Incision wound group (n = 10): Rats in this group were treated under general anesthesia and sterile conditions on day 0.

A full-thickness skin excision was performed with a 3–5 mm incision in the superior palpebrae, and a wound was created. The wound created was left open, cleaned with SF every day, and dressed. In this group (n = 5) on the 3rd day and (n = 5) on the 7th day, they were sacrificed with a high-dose anesthetic for biochemical measurement, blood was taken by cardiac puncture, and a tissue sample was taken from the superior palpebra for histopathological examination. Suture + Quercetin Group (n = 10): On day 0, rats in this group were performed on a full-thickness skin excision with a 3–5 mm incision in the palpebra superior of the right eye under general anesthesia and sterile conditions, and a wound was created. The wound was closed by applying simple separate sutures with 7 − 0 Nylon sutures. Rats in this group were given 1 mg/kg Quercetin once a day through gastric gavage until the end of the study. A tissue sample was taken for histopathological examination from the blood and palpebrae.

A sample has been taken histopathologically and evaluated regarding wound healing.

Using ELISA in a mechanical device, a Rat ELISA kit was used to measure TNF-alfa, S-TNF-l, IL-6, and EGF in tissue and serum. Hyd(hydroxyproline), An analysis of the total oxidant status (TOS) and the total antioxidant status (TAS) of the body assessment were carried out in tissue and blood serum. The histopathological examination of the biopsy material covering the wound healing line was evaluated under a light microscope.

Data analysis

The data analysis was carried out using IBM SPSS Statistics version 25.0 software (IBM Corporation, Armonk, NY, US).

An analysis of Shapiro-Wilk and Levene tests was performed to determine whether the standard distribution and variance homogeneity assumptions were met. We expressed data as mean + SD or median (25th − 75th) percentiles; whenever possible. One-Way ANOVA was used to compare IL-1 and IL-6 levels among study groups, and the Kruskal Wallis test was used to compare Hyd and EGF levels. A post-hoc Tukey HSD or Dunn-Bonferroni test was used when p-values from One-Way ANOVA or Kruskal Wallis test were statistically significant. For the comparison of the continuous variables, the Mann-Whitney U test was applied if the parametric test assumptions were not met. Student t-tests were used to compare the mean differences between follow-up times within each group. It was considered statistically significant if the p-value was less than 0.05. A Bonferroni correction was applied to every possible multiple comparison to control Type I errors.

Among the subjects sacrificed on the 3rd day, the IL-1 protection orientation was intentionally different between the groups (p = 0.016) and the situation causing the difference; Quercetin group had lower IL-1 temperatures than the Sham group (p = 0.025). Among the subjects sacrificed on the 7th day, there was an external difference by limiting the IL-1 environment (p = 0.017) compared to the groups, and the reason for the difference was that IL-1 was lower than the Quercetin standards compared to the Incision group (p = 0.017). 0.016). The Sham, Incision, and Quercetin groups contained no difference between the subjects sacrificed on day 3 and those sacrificed on day 7 according to the Bonferroni correction that went beyond IL-1 (p > 0.0167) (see Fig. 1 and Table 1).

Table 1

Biochemical measurements in terms of study groups and follow-up times
	Sham	Incision	Quercetin	p-value †
IL-1β
3rd day	7.12 ± 1.42^a	6.97 ± 0.79	5.02 ± 0.90^a	0.016¶
7th day	4.98 ± 1.05	5.55 ± 1.01^b	3.54 ± 0.80^b	0.017¶
p-value ‡	0.027¶¶	0.039¶¶	0.025¶¶
IL-6
3rd day	5.44 ± 0.78^c	4.08 ± 0.67^c	4.18 ± 0.57	0.013¶
7th day	5.82 ± 1.12^a	4.56 ± 0.80	3.42 ± 0.64^a	0.004¶
p-value ‡	0.550¶¶	0.339¶¶	0.083¶¶
TNF-α
3rd day	55.64 ± 4.82	54.09 ± 4.52	46.56 ± 6.26	0.040¶
7th day	48.22 ± 2.59^a	45.37 ± 2.18	40.46 ± 3.23^a	0.002¶
p-value ‡	0.016¶¶	0.005¶¶	0.089¶¶
HPO
3rd day	198.23 (184.67-202.87)	202.54 (195.16-208.06)	231.23 (198.01-245.61)	0.208¥
7th day	190.11 (185.28–213.30)	190.76 (183-47-196.17)^b	231.93 (210.12-251.32)^b	0.017¥
p-value ‡	0.690¥¥	0.056¥¥	0.548¥¥
EGF
3rd day	96.78 (91.50-102.16)	95.67 (92.31-101.04)	96.87 (85.44-113.44)	0.932¥
7th day	97.66 (89.11-117.22)	90.32 (79.63–91.61)	100.98 (97.10-116.20)	0.054¥
p-value ‡	0.841¥¥	0.056¥¥	0.421¥¥
TAS
3rd day	10.59 ± 1.15	10.89 ± 1.27	11.82 ± 1.32	0.304¶
7th day	11.26 ± 1.57	11.64 ± 0.88	13.30 ± 1.56	0.082¶
p-value ‡	0.461¶¶	0.311¶¶	0.144¶¶
TOS
3rd day	3.19 ± 0.23	3.12 ± 0.16	2.90 ± 0.13	0.062¶
7th day	3.38 ± 0.26^a	3.21 ± 0.15	2.93 ± 0.10^a	0.007¶
p-value ‡	0.250¶¶	0.353¶¶	0.648¶¶
When appropriate, data are presented as mean + SD or median (25th − 75th) percentiles. † Based on the Bonferroni Correction, p 0.025 was considered statistically significant for comparisons between study groups within each study period. A statistically significant difference was observed between follow-up times within each study group, based upon results from the Bonferroni Correction for comparisons between follow-up times within each study group. Statistical analyses include One-Way ANOVA, Kruskal Wallis test, Student's t-test, and Mann Whitney U test. a: Sham vs Quercetin (p < 0.025), b: Incision vs Quercetin (p < 0.025), c: Sham vs Incision (p = 0.020).

The level of IL-6 differs statistically significantly among the subjects sacrificed on the 3rd day (p = 0.013), the situation causing the said difference; There was a significant reduction in IL-6 levels in the Incision group compared to the Sham group (p = 0.020). Among the subjects sacrificed on the 7th day, there was a statistically significant difference in IL-6 levels according to the groups (p = 0.004 There was a significant difference between the Quercetin group and the Sham group in terms of IL-6 levels (p = 0.003). Within the Sham, Incision, and Quercetin groups, In terms of statistical significance, there was no difference between the subjects sacrificed on day 3 and those sacrificed on day 7 in terms of IL-6 levels according to Bonferroni correction (p > 0.0167) (see Fig. 2 and Table 1).

Among the subjects sacrificed for three days, there was no statistically significant difference between the groups regarding TNF-α levels according to Bonferroni correction (p = 0.040). On the other hand, among the subjects who were sacrificed on the 7th day, there was a statistically significant difference in TNF-α levels according to the groups (p = 0.002). TNF-α levels were lower in the Quercetin group than in the Sham group (p = 0.002). TNF-α levels of the subjects sacrificed on the 7th day were statistically significantly lower than those sacrificed on the 3rd day in the sham group (p = 0.016). TNF-α levels of the subjects sacrificed on the 7th day were statistically significantly lower in the incision group than those sacrificed on the 3rd day (p = 0.005). Finally, TNF-α levels were statistically similar between the subjects sacrificed on day three and those sacrificed on day 7 in the Quercetin group (p = 0.089) (see Fig. 3 and Table 1).

Hyd levels did not differ statistically significantly between the groups among the subjects sacrificed on the 3rd day (p = 0.208). However, there was a statistically significant difference in Hyd levels among the subjects sacrificed on the 7th day compared to the groups (p = 0.017). Hyd levels were higher in the Quercetin group compared to the incision group (p = 0.021). Sham, Incision, and Quercetin groups showed no statistically significant difference in Hyd levels between the 3rd and 7th day sacrificed subjects (p > 0.05) (see Table 1).

As a result of the 3rd-day sacrifice, the EGF levels were not statistically significant among the groups (p = 0.932). There was no statistically significant difference in EGF levels among the groups sacrificed on the 7th day (p = 0.054). Within the Sham, Incision, and Quercetin groups, EGF levels did not differ statistically significantly between subjects sacrificed on the 3rd day and those sacrificed on the 7th day (p > 0.05) (see Table 1).

The TAS levels in the three groups did not differ statistically significantly (p = 0.304). TAS levels were not statistically significantly different between groups of subjects sacrificed on the 7th day (p = 0.082). Within the Sham, Incision, and Quercetin groups, There was no statistically significant difference in TAS levels between the subjects sacrificed on the 3rd day and the subjects sacrificed on the 7th day (p > 0.05). (see Fig. 4 and Table 1).

The TOS levels among the subjects sacrificed on the 3rd day did not differ statistically significantly between the groups (p = 0.062). A statistically significant difference in TOS levels was observed among the subjects sacrificed on the 7th day (p = 0.007). There was a significant reduction in TOS levels in the Quercetin group compared to the Sham group (p = 0.005). Within the Sham, Incision, and Quercetin groups, the TOS levels did not differ statistically significantly between the 3rd and 7th day sacrificed subjects (p > 0.05) (see Fig. 5 and Table 1).

Incision and Sham groups, sacrificed on the third day, had significantly greater levels of IL-1 than controls (p < 0.001). The IL-6 levels of the Sham, Incision, and Quercetin groups, sacrificed on the 3rd day, were also statistically significantly higher than the control group (p < 0.001). TNF-α level of the Sham group sacrificed on the 3rd day was statistically significantly higher than the control group (p = 0.003). The EGF level of the Incision group, which was sacrificed on the 3rd day compared to the control group, was also statistically significantly higher (p = 0.005). There was no statistically significant difference between the control group and the groups sacrificed on the 3rd day in terms of other laboratory measurements, according to Bonferroni correction (p > 0.0083). (see Table 2)

Table 2

The comparisons between 3rd -day measurements and the control group
	Control	Sham	Incision	Quercetin
IL-1	3.83 ± 0.77
3rd day		7.12 ± 1.42	6.97 ± 0.79	5.02 ± 0.90
p-value †¶		< 0.001	< 0.001	0.019
IL-6	2.65 ± 0.39
3rd day		5.44 ± 0.78	4.08 ± 0.67	4.18 ± 0.57
p-value †¶		< 0.001	< 0.001	< 0.001
TNF-α	45.91 ± 4.97
3rd day		55.64 ± 4.82	54.09 ± 4.52	46.56 ± 6.26
p-value †¶		0.003	0.009	0.829
Hyd	190.12 (179.66-202.43)
3rd day		198.23 (184.67-202.87)	202.54 (195.16-208.06)	231.23 (198.01-245.61)
p-value ‡¶		0.594	0.165	0.019
EGF	87.16 (82.52–93.44)
3rd day		96.78 (91.50-102.16)	95.67 (92.31-101.04)	96.87 (85.44-113.44)
p-value ‡¶		0.019	0.005	0.099
TAS	11.50 ± 1.01
3rd day		10.59 ± 1.15	10.89 ± 1.27	11.82 ± 1.32
p-value †¶		0.140	0.331	0.609
TOS	2.94 ± 0.36
3rd day		3.19 ± 0.23	3.12 ± 0.16	2.90 ± 0.13
p-value †¶		0.189	0.325	0.794
The data were expressed as mean + SD or median (25th − 75th) percentiles, depending on the case. † Student’s t-test, ‡ Mann Whitney U test, p = 0.0083 according to the Bonferroni Correction for comparing the control and experimental groups.

The IL-1 levels of the Incision group sacrificed on the 7th day were statistically significantly higher than the control group (p = 0.003). The IL-6 levels of the Sham and Incision groups, which were sacrificed on the 7th day compared to the control group, were also statistically significantly higher (p = 0.002 and p < 0.001). The Hyd level of the Quercetin group sacrificed on the 7th day was statistically significantly higher than the control group (p = 0.005). The EGF level of the Quercetin group sacrificed on the 7th day was also statistically significantly higher than the control group (p < 0.001). There was no statistically significant difference between the control group and the groups sacrificed on the 7th day in terms of other laboratory measurements, according to Bonferroni correction (p > 0.0083). (see Table 3)

Table 3

The comparisons between 7th -day measurements and the control group
	Control	Sham	Incision	Quercetin
IL-1	3.83 ± 0.77
7th day		4.98 ± 1.05	5.55 ± 1.01	3.54 ± 0.80
p-value †¶		0.031	0.003	0.509
IL-6	2.65 ± 0.39
7th day		5.82 ± 1.12	4.56 ± 0.80	3.42 ± 0.64
p-value †¶		0.002	< 0.001	0.011
TNF-α	45.91 ± 4.97
7th day		48.22 ± 2.59	45.37 ± 2.18	40.46 ± 3.23
p-value †¶		0.354	0.822	0.046
Hyd	190.12 (179.66-202.43)
7th day		190.11 (185.28–213.30)	190.76 (183-47-196.17)	231.93 (210.12-251.32)
p-value ‡¶		0.594	0.953	0.005
EGF	87.16 (82.52–93.44)
7th day		97.66 (89.11-117.22)	90.32 (79.63–91.61)	100.98 (97.10-116.20)
p-value ‡¶		0.028	0.768	< 0.001
TAS	11.50 ± 1.01
7th day		11.26 ± 1.57	11.64 ± 0.88	13.30 ± 1.56
p-value †¶		0.730	0.794	0.017
TOS	2.94 ± 0.36
7th day		3.38 ± 0.26	3.21 ± 0.15	2.93 ± 0.10
p-value †¶		0.031	0.134	0.958
Where appropriate, data were shown as mean ± SD or median (25th − 75th) percentiles. † Student’s t-test, ‡ Mann Whitney U test, ¶ The comparison between the control group, according to the Bonferroni Correction p < 0.0083 was considered statistically significant.

Pathology results showed that re-epithelialization and neovascularization between 3. Day and 7. The day was significant in all groups (p < 0.05). Inflammatory cells in the Quercetin group were significantly lower in 3. Day (p < 0.05). The Quercetin group was found effective as a sham group at 3. Day for collagen formation. (see Table 4)

Table 4

*: p < 0,01, a, b, c, d, e: Differences between means with different letters in the same column are significant (p < 0,05).
Groups	Reepithelialization M ± SD	Neovascularization M ± SD	ScarveUlcus M ± SD	Collagen M ± SD	inflammatory cell M ± SD
Control 3. day	2,60^a ± 0,82	0,00^c ± 0,00	0,33^de ± 0,82	1,00^d ± 0,00	0,33^d ± 0,82
Sham 3. day	0,33^b ± 0,52	0,83^b ± 0,41	2,17^a ± 0,41	2,00^c ± 0,63	2,83^a ± 0,41
Incision 3. day	0,16^b ± 0,41	0,50^b ± 0,55	2,33^a ± 0,52	1,00^d ± 0,00	2,83^a ± 0,41
Incision + Quercetin 3.day	0,60^b ± 0,52	0,83^b ± 0,41	2,67^a ± 0,52	2,17^bc ± 0,75	2,50^b ± 0,55
Control 7. day	3,00^a ± 0,00	0,00^c ± 0,00	0,00^e ± 0,00	2,00^c ± 0,00	0,00^d ± 0,00
Sham 7.day	2,17^a ± 1,33	2,67^a ± 0,52	1,50^b ± 0,55	1,67^c ± 0,52	2,00^bc ± 0,00
Incision 7.day	2,67^a ± 0,52	3,00^a ± 0,00	0,83^cd ± 0,41	2,83^a ± 0,41	1,83^c ± 0,41
Incision + Quercetin 7.day	2,50^a ± 0,84	2,67^a ± 0,52	1,17^bc ± 0,41	2,67^ab ± 0,52	1,83^c ± 0,41
P	0,000*	0,000*	0,000*	0,000*	0,000*

The reactive oxygen species (ROS), also known as reactive oxygen intermediates, are essential for preparing a normal wound healing response. Consequently, ROS levels must be maintained at a balance between low and high. Some upcoming treatments aim to control this balance by using antioxidant products. (15)

It has been demonstrated in vitro and in vivo that Quercetin is a flavonol with potent antioxidant properties, anti-inflammatory properties, and anti-fibrotic properties in various tissues.(16,17) There has been increased interest in using Quercetin as a therapeutic in the ocular surface scientific community as a treatment for conditions such as neovascularization of the cornea, inflammation, keratoconus, and dry eye. (17).

During the proliferative phase of wound healing, neovascularization, re-epithelialization, and granulation tissue are observed. A period of several weeks may be required to complete this process. (18) In our study, re-epithelialization and neovascularization occurred between 3. Day and 7. The day was significant in all groups (p < 0.05), as expected in the wound-healing process.

During the inflammatory stage, chemotaxis, an increase in vascular permeability and hemostasis, prevent further damage and closing the wound. A few days are necessary for the inflammatory stage. (18)

In our study, inflammatory cells in the Quercetin group were significantly lower in 3. Day (p < 0.05). IL-1 blood levels and TNF-alfa were significantly lower in the quercetin group (p < 0.05) than in other groups. Also, IL-6 was found to be significantly lower at 7. Day in quercetin group (p < 0.05) in comparison to other groups. It shows the anti-inflammatory properties of Quercetin, which can lead to decreased wound healing time. Inflammatory cells counts between 3. And 7. The day was not significant ( p > 0.05) because the inflammatory stage is an early stage of wound healing.

The Quercetin group is influential as the sham group at 3. Day for collagen formation and hyd value is significantly higher in blood, supporting collagen production in the early stages of wound healing. Our study revealed that Quercetin reduced TOS levels compared to Sham. (p = 0.005). It supports the antioxidant properties of Quercetin.

At this stage, Quercetin was found to be anti-inflammatory and antioxidant in our study; however, it should be supported by future studies before using in clinical treatments

There has been evidence in vitro and in vivo that Quercetin is potently antioxidant, anti-inflammatory, and antifibrotic in various tissues. In this study, Quercetin was investigated for its effects on wound healing in the eyelids, an area that has not been studied before and has fragile skin.

In our study, Quercetin was found to be anti-inflammatory and antioxidant, and these properties can lead to decrease wound healing time, and also Quercetin healed wounds and scavenged free radicals effectively.

Informed Consent: N/A.

Conflict of Interest: The authors have no conflicts of interest to declare.

Financial Disclosure: The authors declared that this study has received no financial support.

Seçil Yigen İritaş ORCID ID: 0000-0003-4462-6526

İlter İritaş, ORCID ID: 0000-0003-1789-4787

Zülfükar Kadir SARITAŞ, ORCID ID :0000-0002-7659-6635

Fatma GÖRÜCÜ, ORCID ID:0000-0001-7630-0788

H.Hüseyin DEMİREL, ORCID ID:0000-0002-4795-2266

Aziz BÜLBÜL, ORCID ID: 0000-0003-0995-3986

Yusuf KOÇ. ORCID ID:0000-0002-6342-5466

Ethics Committee Approval: Ethics committee appoval was received from the AKÜHADYEK (49533702/08).

Author Contribution

seçil yigen iritaş wrote the main manuscript , Seçil Yigen İritaş, İlter İritaş and Kadir Sarıtaş prepared rats and created eyelids wounds ,other authors contributed for biochemical analysis, patological analysis and reviewed the manuscript

Bernstein EF. Reactive oxygen species activate the human elastin promoter in a transgenic model of cutaneous photoaging. Dermatol Surg. 2002;28(2):132-135. doi:10.1046/j.1524-4725.2002.00328.x
Ponugoti B, Xu F, Zhang C, Tian C, Pacios S, Graves DT. FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress. J Cell Biol. 2013;203(2):327-343. doi:10.1083/jcb.201305074
Gottrup F, Agren MS, Karlsmark T. Models for use in wound healing research: a survey focusing on in vitro and in vivo adult soft tissue. Wound Repair Regen. 2000;8(2):83-96. doi:10.1046/j.1524-475x.2000.00083.x.
Mogford JE, Mustoe TA. Experimental models of wound healing. In: Falanga V, editor. Cutaneous wound healing. London: Martin Dunitz, 2001:109–22.
Starace M, Orioni G, Alessandrini A, et al. Digital Ulcers: Multidisciplinary Approach and Dermatological Management. Dermatol Pract Concept. 2023;13(1):e2023019. Published 2023 Jan 1. doi:10.5826/dpc.1301a19
Raffetto JD. The definition of the venous ulcer. J Vasc Surg. 2010;52(5 Suppl):46S-49S. doi:10.1016/j.jvs.2010.05.124
Kant V, Jangir BL, Sharma M, Kumar V, Joshi VG. Topical application of quercetin improves wound repair and regeneration in diabetic rats. Immunopharmacol Immunotoxicol. 2021;43(5):536-553. doi:10.1080/08923973.2021.1950758
Xu F, Zhang C, Graves DT. Abnormal cell responses and role of TNF-α in impaired diabetic wound healing. Biomed Res Int. 2013;2013:754802. doi:10.1155/2013/754802.
Liu R, Bal HS, Desta T, Behl Y, Graves DT. Tumor necrosis factor-alpha mediates diabetes-enhanced apoptosis of matrix-producing cells and impairs diabetic healing. Am J Pathol. 2006;168(3):757-764. doi:10.2353/ajpath.2006.050907
Han YP, Tuan TL, Wu H, Hughes M, Garner WL. TNF-alpha stimulates activation of pro-MMP2 in human skin through NF-(kappa)B mediated induction of MT1-MMP. J Cell Sci. 2001;114(Pt 1):131-139. doi:10.1242/jcs.114.1.131
Khanna S, Biswas S, Shang Y, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One. 2010;5(3):e9539. Published 2010 Mar 4. doi:10.1371/journal.pone.000953911.
Kasiewicz LN, Whitehead KA. Lipid nanoparticles silence tumor necrosis factor α to improve wound healing in diabetic mice. Bioeng Transl Med. 2018;4(1):75-82. Published 2018 Dec 20. doi:10.1002/btm2.10123.
Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol. 2008;17(12):1063-1072. doi:10.1111/j.1600-0625.2008.00786.x.
Gomathi K, Gopinath D, Rafiuddin Ahmed M, Jayakumar R. Quercetin incorporated collagen matrices for dermal wound healing processes in rat. Biomaterials. 2003;24(16):2767-2772. doi:10.1016/s0142-9612(03)00059-0.
McKay TB, Karamichos D. Quercetin and the ocular surface: What we know and where we are going. Exp Biol Med (Maywood). 2017;242(6):565-572. doi:10.1177/1535370216685187
Cheng J, Luo XQ, Chen FS. Quercetin attenuates lipopolysaccharide-mediated inflammatory injury in human nasal epithelial cells via regulating miR-21/DMBT1/NF-κB axis. Immunopharmacol Immunotoxicol. 2022;44(1):7-16. doi:10.1080/08923973.2021.1988963
Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6. doi:10.1126/scitranslmed.3009337Eur J Cell Biol 2002;81:153–60.
Heather A. Wallace, Brandon M. Basehore, Patrick M. Zito.Wound healing phases.In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. 2022 Aug 25. Affiliations expand PMID: 29262065

No competing interests reported.

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Efficacy of Quercetin on rat eyelid wound healing, a randomized, sham-controlled double-blind study

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