N-Acetylcysteine Added to Local Anesthesia Reduces Scar Area and Width in Early Wound Healing—An Animal Model Study

Abstract

The aim of the study was to evaluate if a pre-incisional N-acetylcysteine (NAC) treatment altered the process of wound healing in a rat model. The dorsal skin of 24 Sprague-Dawley rats was incised in six locations. Before the incisions were made, skin was injected either with lidocaine and epinephrine (one side) or with these agents supplemented with 0.015%, 0.03%, or 0.045% NAC (contralaterally). Photographic documentation of the wound healing process was made at 11 time points. Rats were sacrificed 3, 7, 14, or 60 days after incision to excise scars for histological analysis. They included: Abramov scale scoring, histomorphometry analysis, and collagen fiber arrangement assessment. Skin pretreated with 0.03% NAC produced the shortest scars at all analyzed time points, though this result was statistically insignificant. At this NAC concentration the scars had smaller areas on the third day and were narrower on the day 4 compared with all the other groups (p < 0.05). On day 7, at the same concentration of NAC, the scars had a higher superficial concentration index (p = 0.03) and larger dermal proliferation area (p = 0.04). NAC addition to pre-incisional anesthetic solution decreased wound size and width at an early stage of scar formation at all concentrations; however, with optimal results at 0.03% concentration.

Single Dose of N-Acetylcysteine in Local Anesthesia Increases Expression of HIF1α, MAPK1, TGFβ1 and Growth Factors in Rat Wound Healing

“…A lack of differences in the anti-MPO staining suggests that NAC administration does not influence the number of neutrophils migrating to the wound site. This corresponds with the subjective histological assessment results, which showed no significant differences in the severity of inflammation (acute or chronic) between the groups [13].…”

“…A decrease in its expression may be unfavorable; however, no disturbance in the epithelialization or wound closure in the gNAC group was noted. This observation corresponds with the lowered variance of the collagen fibers arrangement at the peri-wound site on the 7th day [13]. On the other hand, we observed an elevated expression of several types of collagens on days 14 and 60.…”

“…The study presents a molecular follow-up of our previous experiment [13]. Briefly, we showed that a single pre-incisional dose of NAC (especially 0.03%) significantly decreased the scar area and width at an early wound healing stage.…”

“…Other pro-angiogenic factors that showed increased expressions in the NAC-treated group were CSF2 and CSF3 (on the 3rd and 60th day) [32,33]. Despite an elevated expression of the previously mentioned factors, an intensified neo-angiogenesis has not been confirmed by the histological assessment [13].…”

“…We hypothesized that, by reducing oxidative stress and the extent of the tissue damage, NAC may alleviate the early inflammation and affect wound healing molecular pathways. The study was performed as an extension of earlier histological observations [13].…”