Gene expression analysis of diabetic foot ulcers reveals the potential impact of Levofloxacin on wound healing

TL;DR

This study shows that Levofloxacin, an antibiotic used for diabetic foot ulcers, may worsen wound healing by increasing oxidative stress and altering key gene expressions.

Contribution

The study is the first to analyze how Levofloxacin affects gene expression in diabetic foot ulcers.

Findings

Levofloxacin significantly increased the expression of TGFβ-1, HMOX-1, NFE2L2, and MMP-9 genes.

The observed gene expression changes suggest Levofloxacin may induce oxidative stress in diabetic patients.

Altered gene activity could impair wound healing by disrupting oxidative stress and inflammatory pathways.

Abstract

Chronic nonhealing wounds in diabetic patients represent a significant and persistent clinical challenge, contributing to the increased morbidity and mortality of patients with diabetes worldwide. The selection of an appropriate treatment strategy is crucial for mitigating these challenges and enhancing clinical outcomes. While antibiotics are commonly employed to manage infections associated with diabetic foot ulcers (DFUs), their over prescription and prolong use remains a contentious issue. There is evidence linking antibiotics to the induction of oxidative stress, which aggravates the already disrupted redox balance in diabetic patients, thereby worsening their cellular functions. However, the molecular mechanisms and effects of these antibiotics on the expression profiles of genes have not been studied before. Therefore, the present study aimed to analyze alterations in the expression of key wound healing-related genes, such as TGFΒ-1, NFE2L2 (also called Nrf2), HMOX1, and MMP-9, following Levofloxacin use in patients with DFUs. Biopsy samples were collected from a cohort of 30 participants and categorized into three groups: DFUs treated with antibiotics (DFU + Ab), DFUs without antibiotics (DFU-Ab), and a control group (C). The gene expression levels were evaluated via reverse transcriptase quantitative PCR (RT‒qPCR). Our findings revealed a significant (p < 0.05) increase in the expression of TGFβ-1, HMOX-1, NFE2L2, and MMP-9 in the presence of antibiotic (Levofloxacin). The increase in the expression of these genes suggests that antibiotics may induce oxidative stress, leading to biological changes through altering the expression of genes involved in oxidative stress and the inflammatory pathway, thus impacting the wound healing process.

Chronic nonhealing woundleading to Diabetic Foot Ulcers (DFUs) represent a significant clinical challenge in diabetic patients.While antibiotic therapy is commonly administered to manage infections and facilitate wound healing, its role in inducing oxidative stress remains a subject of ongoing debate.Antibiotic-induced disruption of redox homeostasis may impair cellular functions by modulating oxidative stress and inflammatory pathways, thereby influencing the wound healing process.

Chronic nonhealing woundleading to Diabetic Foot Ulcers (DFUs) represent a significant clinical challenge in diabetic patients.

While antibiotic therapy is commonly administered to manage infections and facilitate wound healing, its role in inducing oxidative stress remains a subject of ongoing debate.

Antibiotic-induced disruption of redox homeostasis may impair cellular functions by modulating oxidative stress and inflammatory pathways, thereby influencing the wound healing process.

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