# Evaluation of enteral and parenteral hyaluronic acid in induced ischemic skin flaps in rats: a double-blinded and randomized study

## TL;DR

This study evaluates how hyaluronic acid administered through different routes affects healing in rat skin flaps with reduced blood flow.

## Contribution

The study compares enteral and parenteral administration of hyaluronic acid in ischemic skin flaps using clinical, histological, and cytokine data in rats.

## Key findings

- Subcutaneous hyaluronic acid (0.3%) reduced necrosis and improved epithelialization in ischemic skin flaps.
- Both enteral and parenteral hyaluronic acid showed beneficial effects on inflammation and tissue healing.
- Pro- and anti-inflammatory cytokines varied significantly between treatment groups.

## Abstract

To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers.

Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10.

A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05).

High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization.