Effects of Cigarette Smoke in Mice Wound Healing is Strain Dependent

Histology and Embryology Department, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Toxicologic Pathology (Impact Factor: 2.14). 02/2007; 35(7):890-6. DOI: 10.1080/01926230701459986
Source: PubMed


It has been clinically and experimentally shown that cigarette smokers suffer from impaired wound healing, but the mechanisms that lead to the alterations are not well understood. The aim of this study was to investigate if the effects of cigarette smoke exposure on excisional cutaneous wound healing are different depending on the strain (Swiss, BALB/c and C57BL/6 mice) studied. Male mice were exposed to smoke of nine whole cigarettes per day, 3 times/day, daily, for 10 days. In the 11th day a full-thickness excisional wound was performed. Control group was sham-exposed and also had a full-thickness excisional wound. The cigarette smoke exposure protocol was performed until euthanasia. Animals were euthanatized 14 days after wounding. Wound contraction was evaluated 7 and 14 days after lesion. Sections were stained with hematoxylin-eosin, Sirius red or toluidine blue and immunostained for alpha-smooth muscle actin. Smoke exposed animals presented delay in wound contraction, in fibroblastic and inflammatory cells recruitment and in myofibroblastic differentiation; those alterations were strain dependent. Cigarette smoke exposure also affected mast cells recruitment and neoepidermis thickness. In conclusion, the present study demonstrated that the effects of cigarette smoke in mice cutaneous wound healing are related to mice strain studied.

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Available from: Luís Cristóvão Porto, Oct 07, 2015
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    • "It is known that mast cells, which are found in conjunctive tissue, are mobilized during wound healing and participate in all phases of the process [23], especially in the inflammatory phase, because these cells are the first to release inflammatory mediators involved in vasodilatation [1, 23] and the recruitment and increased survival of leukocytes [23]. However, it has been shown that prolonged mobilization of mast cells until 21 days after wound formation can damage the formation of granulation tissue [24] and that an excess of mast cell mediators (such as kinases) may delay the migration of epithelial cells [25, 26]. According to Barroso et al. [23], propolis has potential anti-inflammatory effects in acute inflammation and reduces the number of mast cells, but it does not have the same effect in the later stages of repair. "
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    ABSTRACT: Capybara oil is commonly used for cutaneous wound healing in traditional South American medicine, although its beneficial effect has never been experimentally proven. The aim of this study was to investigate the effects of the topical application of capybara oil on skin wounds in Swiss mice. The following characteristics of the wounds were observed and evaluated: wound contraction and reepithelialization, the number of polymorphonuclear leukocytes and mast cells, the thickness of the neoepidermis, and the distribution of collagen and elastic fibers. Our study showed that oil extracted from subcutaneous capybara fat was beneficial for wound healing, indicating that capybara oil plays an important role in promoting tissue repair.
    Evidence-based Complementary and Alternative Medicine 06/2013; 2013(1):217198. DOI:10.1155/2013/217198 · 1.88 Impact Factor
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    • "In each strain, animals were separated in control (n ¼ 10) and smoke-exposed (n ¼ 14) groups. Smoke-exposed groups had the whole body exposed, in an inhalation chamber, to a smoke–air mixture of commercial filtered Virginia cigarettes, three times per day, seven days per week, during the entire experiment, as previously described (Cardoso et al. 2007; Valenca et al. 2004). The cigarette smoke exposure protocol started ten days before the excisional wound and continued until the end of the experiment. "
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    ABSTRACT: Cigarette smoke has been associated with poor healing in several studies, but the precise mechanisms involving this impairment are still not elucidated. The aim of this work was to investigate cigarette smoke exposure effects on initial phases of cutaneous healing in mice, focusing mainly on gene expression of two molecules involved in wound repair (Ccn2/Ctgf and Tgfb1) and to study if these effects are strain dependent. Mice were exposed to the smoke of nine cigarettes per day, three times per day, for ten days. In the eleventh day an excisional wound was made. The control group was sham-exposed. The cigarette smoke exposure protocol was performed until euthanasia, seven days after wounding. Wound contraction was evaluated. Sections were stained with hematoxylin-eosin, Sirius red, and toluidine blue, and also immunostained for alpha-smooth muscle actin. Gene expression of Ccn2/Ctgf and Tgfb1 was evaluated by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Smoke-exposed animals presented delay in wound contraction; fibroblastic, inflammatory, and mast cell recruitment; re-epithelialization; myofibroblastic differentiation; and Ccn2/Ctgf and Tgfb1 gene expression. Those alterations were strain dependent. This work confirmed the deleterious effects of cigarette smoke exposure on mouse cutaneous healing depending on mouse strain and links these effects to an overexpression of Ccn2/Ctgf.
    Toxicologic Pathology 02/2009; 37(2):175-82. DOI:10.1177/0192623308328134 · 2.14 Impact Factor
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    • "Mouse strain variations in inflammation and wound healing have also been reported. The affect of cigarette smoke on the healing of skin wounds was tested in BALB/c, C56BL6, and Swiss mice (Cardoso, et al., 2007). Contraction of skin wounds in BALB/c and C57BL6 was inhibited compared to Swiss mice and each strain had is own distinct inflammatory response to injury and to cigarette smoke. "
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    ABSTRACT: Genetically engineered mice are usually produced on a mixed genetic background and can be derived from several mouse strains including 129SvJ, C57BL6, and BALB/c. To determine whether differences in recurrent corneal epithelial erosions (RCEEs), corneal epithelial stem cell deficiency (CESCD), and cell migration rate vary between two different mouse strains (BALB/c and C57BL6), 8-week mice were subjected to 1.5 (small) or 2.8mm (large) manual debridement wounds and allowed to heal for 4 weeks. Syndecan-1 (sdc-1) null mice backcrossed seven generations onto a BALB/c genetic background were also included in the RCEE and CESCD studies to permit comparisons between genotypes within a single strain. After sacrifice, corneas were assessed for the presence of recurrent erosions; no fewer than 15 corneas were used for each strain or genotype studied. Data show that the frequency of recurrent erosions after small wounds was 81+/-9% in the C57BL6 mice, 73+/-2% in the BALB/c mice, and 32+/-6% in sdc-1 null mice. Neither strain developed CESCD after small wounds. The frequency of erosions after large wounds was greater (88+/-8%) in the C57BL6 mice compared to BALB/c (60+/-2%), and sdc-1 null mice (32+/-5%). Four weeks after the large wounds, fixed, flat mounted corneas were assessed for evidence of CESCD with antibodies against the conjunctival keratin K8 and the goblet cell marker, the mucin Muc5AC. The frequency of CESCD 4 weeks after the large wounds was significantly greater in the C57BL6 mice than in the BALB/c or sdc-1 null mice. To assess cell migration rates, corneas were subjected to 1.5mm wounds and allowed to heal for 12, 15, 18, 21, and 24h. After sacrifice, corneas were stained with Richardson stain (BALB/c) or propidium iodide (C57BL6) to assess reepithelialization rates. While reepithelialization rates were similar for the early times after wounding, by 24h the C57BL6 corneas had healed faster: 16 of 30 corneas from the C57BL6 mice were closed compared to 9 of 30 of the BALB/c wounds. BALB/c corneas appeared larger overall compared to C57BL6 corneas; measurements of the overall mass of the enucleated eyes and diameters of the flat-mounted corneas confirmed that C57BL6 eyes and corneas were 6.8% and 4.4% smaller respectively than those of BALB/c mice even though the masses of the two mouse strains at 8 weeks of age were identical. Using BrdU to label dividing cells, we found that 18 h after wounding, C57BL6 and BALB/c corneal epithelia showed similar numbers of proliferating cells. To determine if the enhanced corneal epithelial cell migration rate seen in the C57BL6 mice was specific to the cornea, we conducted time-lapse studies to assess random cell migration rates in vitro using primary cultures of mouse epidermal keratinocytes. Consistent with the in vivo data, epidermal keratinocytes derived from BALB/c mice migrated 60% slower than C57BL6 cells. These data prove that strain-specific differences in cell migration rate in vivo are present in the cornea and are accompanied by differences in the frequencies of recurrent erosions and corneal epithelial stem cell deficiency.
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