Effect of Topical Sildenafil on Wound Healing and Oxidative Stress in Rats

Available online 5 April 2024, 111525

Author links open overlay panel, AbstractBackground

In this study, the effects of topical sildenafil applications on oxidative damage levels and antioxidative metabolism and their contribution to wound healing and treatment were investigated.

Materials and Methods

A total of 24 healthy male rats aged 16-18 weeks, each weighing 200-250 g, were randomly divided into three groups: Group A received a saline solution, Group B received an epithelializing cream, and Group C received sildenafil cream. Following skin preparation and anesthesia, 6 mm diameter punch biopsies created wounds on the rats' backs. The treatment protocol involved daily topical dressing for seven days, after which tissue and blood samples were collected for analysis. Tissue samples underwent histopathological examination, while malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities in wound tissue and blood samples were measured.

Results

The wound surface area created by the punch decreased in all groups by the end of the seventh day; However, the degree of wound healing differed in favor of the sildenafil cream group. Histopathologically, according to Greenhalgh's Modified Wound Healing Scoring System, all findings were graded. In the Anova test, the differences between glutathione peroxidase, catalase, and malondialdehyde levels in the serum and tissue of rats was statistically significant (P <0.05), whereas superoxide dismutase levels were not statistically significant (P> 0.05). In the Bonferroni test, the serum CAT levels between groups A and C (P=0.003), between groups B and C (P=0.035), and the serum MDA levels between groups A and B (P=0.018) and between groups A and C (P=0.001) were found to be significant statistically. By the way, the results between tissue CAT levels in the B and C groups (P=0.020) and between tissue GPx levels (P=0.001) in all groups were also significant statistically.

Conclusions

The study findings indicated that topical application of sildenafil led to noteworthy alterations in serum and tissue antioxidative metabolism as well as oxidative damage levels among rats with induced wounds. Sildenafil may be useful in wound treatment; it has been concluded that it is capable of directing new studies to be carried out.

Section snippetsINTRODUCTION

Wound healing is a repair process in which mechanisms at the tissue, cellular and biochemical level play a role in restoring anatomical and physiological features of tissue with impaired integrity. Regardless of the reason the wound is formed, one of the prominent factors during the healing phase is the presence and severity of oxidative stress in terms of biochemical aspects [1]. The intensity of oxidative stress causes excessive inflammation of the wound area. The severity of the inflammation

Wound Healing Process

The wound surface area created by the punch decreased in all groups by the end of the seventh day; However, the degree of wound healing differed in favor of the sildenafil group. At the end of the seventh day, reepithelialization had not occurred in all wounds in the control group.

Histopathological Findings

A (Control) Group: There was no improvement in 3 of them, the epithelium was insufficient in 1 case, and it was formed but thin in 2 cases. The epidermis was intact in 2 of the cases, and reepithelialization was

DISCUSSION

The skin is the first barrier that separates the organism from the external environment. Delayed wound healing can be life-threatening for living organisms. Delayed healing processes can be observed in animals under certain conditions, such as advanced age, diabetes, and immunosuppression [19], [20].

The effects of topical sildenafil (25 mg) on wounds in rats were investigated [21]. In the treated group, it decreased to 15% of the original size 7 days after injury, while significantly delayed

CONCLUSION

The study findings indicated that topical application of sildenafil led to noteworthy alterations in the serum and tissue antioxidative metabolism as well as oxidative damage levels among rats with induced wounds. Histopathological analysis revealed a favorable impact of sildenafil on wound healing. Nevertheless, to achieve complete reepithelialization and address inflamed cells in the deep dermis tissues, it is suggested that the duration of drug application to the wound should be extended.

Funding

This study was supported by grants from Sivas Cumhuriyet University Scientific Research Projects Center (Project number V-057).

CRediT authorship contribution statement

Arda Selin TUNÇ: Writing – review & editing, Writing – original draft, Methodology, Formal analysis, Data curation. Nazlı ERCAN: Validation, Supervision, Methodology, Funding acquisition, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The study was presented orally at 2nd International Conference on “Veterinary Biochemistry and Clinical Biochemistry: Advances and Challenges in Understanding the Mechanism of Diseases 2019” in Ankara, Turkey.

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