Nano-Zinc Oxide Induced Pancreatic Toxicity and The Ameliorating Role of Naringenin: Histological and immunohistochemical study

A. Sewelam, M. Shehata
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Abstract

Background: Though Nano-zinc oxide particles (ZnO NPs) are widely applied in biomedicine, bioengineering and cosmetology, a controversy developed between ZnO NPs benefits versus toxicity on biological systems. Naringenin is a natural antioxidant flavonoid. Objective: to explore the histological and immunohistochemical alterations in the rat pancreas following intraperitoneal exposure to two different doses of 35 nm ZnO NPs and to assess the ameliorating role of Naringenin.Materials and Methods: Forty-five adult male rats were split randomly into five groups. Group1 served as control. Groups2 and 4 received a single intraperitoneal injection of 250 and 700 mg/kgbw ZnO NPs. Groups3 and 5 administered ZnO NPs as previously described followed by Naringenin gavaged at a dose of 20mg/kgbw/day once daily for 14 consecutive days. Histological, immunohistochemistry, biochemistry, and morphometry studies were accessed in the pancreatic tissue gained from all animals under the study. Results: Contrasted to the group of control, ZnO NPs exhibited a dose dependent pancreatic tissue and cellular damage manifested as vascular congestion, duct dilatation, fibrosis, and inflammatory cell infiltration. Also, both acinar and B-cells showed degenerating changes varied from just cytoplasmic vacuolization in the ZnO NPs(250mg)-treated rats to severe cell shrinking, pyknosis, cytoplasmic and nuclear fragmentation in the ZnO NPs(700mg)-treated rats. Moreover, ZnO NPs provoked significantly increased mean area percentage of collagen fiber deposition and caspase immunoexpressing, significantly raised fasting blood glucose, serum amylase, lipase and MDA levels besides significant decline regarding insulin immunoexpressing. Naringenin administration induced a great recovery concerning the ZnO NPs (250mg)-treated rats but partial recovery regarding the ZnO NPs (700mg)-treated rats. Conclusion: ZnO NPs potentially persuaded an oxidating stress manifest as structural and functional toxicity in the rat pancreas with great reversibility by Naringenin coadministration. A future work concerning ZnO NPs toxicity on vital organs and Naringenin role in opposing this impact is recommended.
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纳米氧化锌诱导胰腺毒性及柚皮素的改善作用:组织学和免疫组织化学研究
背景:虽然纳米氧化锌颗粒(ZnO NPs)在生物医学、生物工程和美容等领域有着广泛的应用,但其对生物系统的益处与毒性一直存在争议。柚皮素是一种天然的抗氧化剂类黄酮。目的:探讨两种不同剂量35 nm氧化锌NPs腹腔注射对大鼠胰腺组织和免疫组织化学的影响,并评价柚皮素的改善作用。材料与方法:将45只成年雄性大鼠随机分为5组。组1作为对照组。第2组和第4组分别腹腔注射250和700 mg/kgbw ZnO NPs。第3组和第5组按上述方法给予氧化锌NPs,然后以20mg/kgbw/day的剂量灌胃柚皮素,每天1次,连续14天。对研究中所有动物的胰腺组织进行了组织学、免疫组织化学、生物化学和形态计量学研究。结果:与对照组相比,ZnO NPs表现出剂量依赖性的胰腺组织和细胞损伤,表现为血管充血、导管扩张、纤维化和炎症细胞浸润。同时,注射氧化锌NPs(250mg)的大鼠的腺泡和b细胞均表现出退行性改变,从细胞质空泡化到严重的细胞萎缩、固缩、细胞质和细胞核碎裂。氧化锌NPs显著增加了胶原纤维沉积和caspase免疫表达的平均面积百分比,显著提高了空腹血糖、血清淀粉酶、脂肪酶和MDA水平,显著降低了胰岛素免疫表达水平。柚皮素对氧化锌NPs (250mg)处理的大鼠有很大的恢复作用,而对氧化锌NPs (700mg)处理的大鼠有部分恢复作用。结论:柚皮素对氧化锌NPs具有诱导大鼠胰腺氧化应激的结构和功能毒性作用,且具有较强的可逆性。建议今后进一步研究氧化锌NPs对重要器官的毒性以及柚皮素的抗毒性作用。
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