Protective effects of Bacillus clausii in cyclophosphamide-induced immunosuppression and intestinal mucositis in rats: histopathological and inflammatory evaluation.

چکیده اصلی

BACKGROUND: Bacillus clausii (B. clausii) is a Gram-positive, spore-forming probiotic widely used for the prevention and treatment of gastrointestinal disorders and may have protective effects against chemotherapy-induced intestinal mucositis. Cyclophosphamide (CP) can induce immunosuppression and intestinal mucosal injury, leading to inflammation and alterations in intestinal homeostasis. This study evaluated the protective effects of B. clausii on intestinal histopathology, inflammation, pro-inflammatory cytokines, and miR-146a expression in a rat model of CP-induced immunosuppression and intestinal mucositis. METHODS AND RESULTS: Thirty-two male Wistar albino rats were randomly allocated into four groups: Group 1 (Control), Group 2 (CP + saline), Group 3 (saline + B. clausii), and Group 4 (CP + B. clausii). Immunosuppression and intestinal mucositis were induced by intraperitoneal CP administration, followed by oral B. clausii treatment. Clinical findings, hematological parameters, histopathology, histomorphometry, cytokine levels, and gene expression were assessed. CP administration impaired body weight gain, altered stool consistency, reduced leukocyte and lymphocyte counts, and caused intestinal mucosal injury with villus shortening, epithelial disruption, inflammatory infiltration, fibrosis, and goblet cell depletion. Villus length decreased by 10.58% and goblet cell count by 44.20% in Group 2 compared with Group 1 (P < 0.001). In Group 4, villus length and goblet cell count increased by 17.81% and 66.34%, respectively, compared with Group 2 (P < 0.001). B. clausii also improved stool consistency, partially restored leukocyte parameters, preserved mucosal architecture, and reduced inflammatory infiltration and fibrosis. Furthermore, B. clausii attenuated CP-induced increases in TNF-α and IL-6, whereas miR-146a expression remained reduced in CP-treated groups. CONCLUSIONS: B. clausii partially attenuated cyclophosphamide-induced intestinal mucositis by improving clinical and histopathological findings, preserving intestinal morphology, restoring goblet cell numbers, and reducing TNF-α and IL-6 levels. The partial recovery of leukocyte and lymphocyte counts suggests potential immunomodulatory effects. Although miR-146a expression was reduced in CP-treated groups, the mechanisms underlying the protective effects of B. clausii remain unclear. Overall, B. clausii may represent a promising supportive probiotic approach for mitigating chemotherapy-induced intestinal mucosal injury. Further mechanistic and clinical studies are warranted to clarify its effects on miR-146a, the intestinal microbiota, inflammatory pathways, and intestinal barrier function.

ترجمه فارسی چکیده

باسیلوس کلسی (B. clausii) یک پروبیوتیک گرم مثبت و تشکیل‌دهنده اسپور است که برای پیشگیری و درمان اختلالات گوارشی استفاده می‌شود. این مطالعه اثرات محافظتی B. clausii بر هیستوپاتولوژی، التهاب، سیتوکین‌های پروالتهابی و بیان miR-146a را در مدل موشی سیکلوفسفامید (CP) ارزیابی کرد. ۳۲ نر موش سفید وستار به چهار گروه تصادفی تقسیم شدند: گروه کنترل، گروه CP + نمک، گروه نمک + B. clausii و گروه CP + B. clausii. CP باعث کاهش وزن بدن، تغییر بافت مدفوع، کاهش شمارش گلبول سفید و لنفوسیت و آسیب بافت مخاطی روده شد. B. clausii با افزایش طول برجستگی و تعداد سلول‌های مخاطی، بهبود بافت مدفوع و کاهش سیتوکین‌های TNF-α و IL-6، بخشی از آسیب‌ها را جبران کرد. میزان miR-146a در گروه‌های درمان شده با CP کاهش یافت.

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