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口服黑种草籽油可减轻砷诱导的大鼠肠道氧化还原失衡、DNA 损伤、代谢紊乱和组织病理学改变。

Oral administration of Nigella sativa oil attenuates arsenic-induced redox imbalance, DNA damage, metabolic distress, and histopathological alterations in rat intestine.

机构信息

Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India.

Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, U.P., India.

出版信息

J Trace Elem Med Biol. 2023 Sep;79:127238. doi: 10.1016/j.jtemb.2023.127238. Epub 2023 Jun 3.

DOI:10.1016/j.jtemb.2023.127238
PMID:37343449
Abstract

BACKGROUND

Exposure to arsenic, a widespread environmental toxin, produces multiple organ toxicity, including gastrointestinal toxicity. Nigella sativa (NS) has long been revered for its numerous health benefits under normal and pathological states. In view of this, the present study attempts to evaluate the protective efficacy of orally administered Nigella sativa oil (NSO) against arsenic-induced cytotoxic and genotoxic alterations in rat intestine and elucidate the underlying mechanism of its action.

METHODS

Rats were categorized into the control, NaAs, NSO, and NaAs+NSO groups. After pre-treatment of rats in the NaAs+NSO and NSO groups daily with NSO (2 ml/kg bwt, orally) for 14 days, NSO treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. Various biochemical parameters, such as enzymatic and non-enzymatic antioxidants, carbohydrate metabolic and brush border membrane marker enzyme activities were evaluated in the mucosal homogenates of all the groups. Intestinal brush border membrane vesicles (BBMV) were isolated, and the activities of membrane marker enzyme viz. ALP, GGTase, LAP, and sucrase were determined. Further, the effect on kinetic parameters viz K (Michaelis-Menten constant) and V of these enzymes was assessed. Integrity of enterocyte DNA was examined using the comet assay. Histopathology of the intestines was performed to evaluate the histoarchitectural alterations induced by chronic arsenic exposure and/or NSO supplementation. Arsenic accumulation in the intestine was studied by inductively coupled plasma-mass spectroscopy (ICP-MS).

RESULTS

NaAs treatment caused substantial changes in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in the intestinal mucosal homogenates. The isolated BBM vesicles (BBMV) also showed marked suppression in the marker enzyme activities. Severe DNA damage and mucosal arsenic accumulation were observed in rats treated with NaAs alone. In contrast, oral NSO supplementation significantly alleviated all the adverse alterations induced by NaAs treatment. Histopathological examination supported the biochemical findings.

CONCLUSION

NSO, by improving the antioxidant status and energy metabolism, could significantly alter the ability of the intestine to protect against free radical-mediated arsenic toxicity in intestine. Thus, NSO may have an excellent scope in managing gastrointestinal distress in arsenic intoxication.

摘要

背景

砷是一种广泛存在的环境毒素,接触砷会导致多种器官毒性,包括胃肠道毒性。黑种草(NS)长期以来因其在正常和病理状态下的众多健康益处而受到推崇。有鉴于此,本研究试图评估口服黑种草油(NSO)对大鼠肠道中砷诱导的细胞毒性和遗传毒性改变的保护作用,并阐明其作用机制。

方法

将大鼠分为对照组、NaAs 组、NSO 组和 NaAs+NSO 组。在 NaAs+NSO 和 NSO 组大鼠每日用 NSO(2 ml/kg bwt,口服)预处理 14 天后,继续用 NSO 治疗 30 天,同时分别用和不用 NaAs 处理(5 mg/kg bwt,口服)。评估各组黏膜匀浆中的各种生化参数,如酶和非酶抗氧化剂、碳水化合物代谢和刷状缘膜标记酶的活性。分离肠刷状缘膜囊泡(BBMV),并测定膜标记酶如碱性磷酸酶(ALP)、谷氨酰转肽酶(GGTase)、亮氨酸氨基肽酶(LAP)和蔗糖酶的活性。进一步评估这些酶的动力学参数 K(米氏常数)和 V 的变化。采用彗星试验检测肠上皮细胞 DNA 的完整性。通过诱导耦合等离子体质谱法(ICP-MS)研究肠道内砷的积累。

结果

NaAs 处理导致肠道黏膜匀浆中刷状缘膜(BBM)、碳水化合物代谢和抗氧化防御酶的活性发生显著变化。分离的 BBM 囊泡(BBMV)也显示出标记酶活性的显著抑制。单独用 NaAs 处理的大鼠观察到严重的 DNA 损伤和黏膜砷积累。相比之下,口服 NSO 补充剂可显著减轻 NaAs 处理引起的所有不良变化。组织病理学检查支持生化发现。

结论

NSO 通过改善抗氧化状态和能量代谢,可以显著改变肠道对抗自由基介导的砷毒性的能力。因此,NSO 在治疗砷中毒引起的胃肠道不适方面可能具有极好的应用前景。

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