The influence of some azoles on wound healing in albino rats

Abstract

Wound healing, a common clinical entity contemporary to human beings, has been recognized to be influenced by several factors such as nutrients like vit-C, zinc, and hormones like GH, insulin, etc. Products of traditionally used plants such as Bryophyllum pinnatum [1] and Moringa oleifera [2] have also been reported to promote healing in experimental animals, probably by virtue of their antimicrobial activity. Because it is well known that infection interferes with healing, antimicrobials are expected to suppress infection and promote healing process only in infected wounds. Antimicrobials are routinely administered pre-and post-surgically and metronidazole, a commonly used antiprotozoal for surgical chemoprophylaxis against anaerobes, is likely to influence the surgical outcome. However, metronidazole (MTZ) has been reported to delay the healing process in dead space wounds [3] and reduce the breaking strength of facial wounds. [4] Recently, MTZ has been reported to possess a potent anti-oxidant property that augments healing process in burns. [5] Similarly, tinidazole (TNZ) has also been reported to suppress healing of dead space wounds, [3] whereas fluconazole (FLZ), a related antifungal azole, has been shown to enhance epithelization. [13] There are no reports on the influence of ketoconazole (KCZ) on wound healing, an antifungal related to fluconazole.

Metronidazole concentration in the bloodstream following its topical application, at different concentration levels, on experimental skin wounds during healing by secondary intention

“…In studies with experimental animals, metronidazole solutions at a dosage of 20mg/kg resulted in delayed healing 16 . A similar effect was reported for a dosage of 160mg/kg 13 . Dosages higher than 20 and lower than 160mg/kg promoted an increase of granulation tissue and epithelialization 10 , 12 - 15 .…”

“…The wide variation of metronidazole concentrations for topical use at the experimental level is an additional difficulty. There are studies that report the effects of metronidazole on healing using 20mg/kg 16 , 50mg/kg 14 , 108 mg/kg 10 , 160mg/kg 13 and 180mg/kg 12 .…”

“…Furthermore, metronidazole can have a favorable influence on skin healing, accelerating epithelialization, reducing repair time 10 - 13 . In general, the results show the favoring of early re-epithelization 12 - 15 , although the granulation and reepithelization time are apparently not influenced by the form of the doses used.…”

Effect of metronidazole on placental and fetal development in albino rats

“…Several studies have demonstrated the action of metronidazole administered orally at a dose of 180mg/kg in the tissue repair process, accelerating wound contraction, collagen synthesis and epithelialization and promoting precocity in cicatrization by directly stimulating fibroblasts, the main cells involved in this process. However, higher doses of this drug may produce cytotoxicity in these cells (Rao et al, 2002;Girish and Patil, 2005), by preventing the synthesis of collagen, elastin, fibronectin, glycosaminoglycans and proteases necessary for tissue remodeling during healing (Amadeu et al, 2003;Hildebrand et al, 2005). Also, there are indications that metronidazole does not act directly on the fibroblasts, but rather diminishes the duration of the inflammatory phase, allowing the cells to speed up the healing process (Sampaio et al, 2009), which was reinforced by our study, since there were no sign of inflammatory processes in the implantation sites as well as in the placentas.…”