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Abstract im: To follow the sequential expression of Myo D (a marker for muscle stem cell differentiation) in the DMBA-painted hamster buccal pouches, following thymoquinone i.p injections. Material and Methods: Eighty male golden Syrian hamsters were divided into 3 groups: group I: (10 anim als) served as negative control, 5 hamsters were scarified before starting the experiment, and the other 5 at the end of the experiment. group II: (10 animals) positive control (the left buccal pouches were painted with the carcinogen 0.5% DMBA 3/wk / 6 weeks, 5 hamsters were sacrificed at second day of last painting and 5 hamsters 2 weeks later. group III: (60 animals) the experimental group: were painted with DMBA as in group II, and then were subdivided into two subgroups as follows: IIIa: (30 animals) one i.p. injection with thymoquinone (0.1 mg/kg body weight). And IIIb: (30 animals) two i.p. injections with thymoquinone (0.1 mg/kg body weight). Blood samples were withdrawn for evaluation of TNF-α level before sacrificing. 5 animals from the TQ treated groups were sacrificed at 4, 24, 48 hrs, one week and two weeks after the last injection. All buccal pouches were surgically excised, fixed, and processed for H&E, and Myo D immunohistochemical (IHC) stains. Results: TQ had shown strong muscle regenerative effect reflected in elongation of the buccal pouch shortening secondary to the carcinogen painting. Serum TNF-α was significantly elevated after 6 weeks of DMBA as compare to the negative control group, and higher significant elevation following one i.p. TQ injection as compared to all experimental groups. Two i.p. TQ injections resulted in significant elevation that declined to near the DMBA-only group. Myo D was only expressed in perivascular mononuclear cells at area of muscle fibers’ regeneration, in the TQ treated groups, at all time intervals . where after two weeks, elongation of the DMBA painted pouches was achieved to near normal control pouches. Myo D (+ve) cells were seen in MFs nuclei after 1&2 wks of two i.p TQ injections, most muscle fibers were mature (peripherally-located nuclei), so were Myo D (-ve). The rest of TQ injected animals Myo D (+ve) cells were seen in perivascular MCs, in other TQ injected groups at all time paints. Conclusion: TQ, as an anti-inflammatory phytochemical, in the specified concentration, and route of administration had resulted in highly significant elevation of serum TNF-α after one injection, as compared to (-ve) & (+ve) control groups, and was comparable to the (+ve) experimental group after 2 weeks of 2 i.p injections. Expulsion of local inflammatory cells from epithelium was recorded after 2days of one i.p II TQ injection. Furthermore, TQ had promising effect to induce regeneration of the striated muscle layer, resulting in elongation of the DMBA-treated pouches to near normal length. It appears that the myogenic effect of TQ could be mediated through:-a- Activating transition of fibroblasts, in the thickened lamina propria, to the myogenic lineage. b- Activating FAP cells from adipocyte cells to myogenic the lineage. c- Recruiting what seem to be bone-marrow stem cells to the area of muscle regeneration, where they were Myo D (+ve). d- Stimulating what could be resident anti-inflammatory macrophages (M2) to the myogenic lineage |