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不同给药途径导致肝脏亚急性镉中毒时不同程度的氧化损伤和组织紊乱。

Different Routes of Administration Lead to Different Oxidative Damage and Tissue Disorganization Levels on the Subacute Cadmium Toxicity in the Liver.

作者信息

Mouro Viviane Gorete Silveira, Ladeira Luiz Carlos Maia, Lozi Amanda Alves, de Medeiros Thiago Soares, Silva Mariany Ribeiro, de Oliveira Elizabeth Lopes, de Melo Fabiana Cristina Silveira Alves, da Matta Sérgio Luis Pinto

机构信息

Department of General Biology, Federal University of Viçosa, Viçosa, MG, 36570-900, Brazil.

Department of Pharmacy, Faculty Univertix, Matipó, MG, 35367-000, Brazil.

出版信息

Biol Trace Elem Res. 2021 Dec;199(12):4624-4634. doi: 10.1007/s12011-020-02570-5. Epub 2021 Jan 5.

Abstract

The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.

摘要

镉(Cd)对肝脏参数的毒性作用在文献中已有广泛描述。实验模型通常采用腹腔注射途径(i.p.),因为这种途径更容易实施,而在口服途径中,人体镉中毒的最佳表现是让金属通过消化系统并被吸收进入血液。因此,本研究通过比较腹腔注射和口服两种途径(单次剂量以及分次剂量的口服途径),来探究镉暴露对肝脏的影响。瑞士成年雄性小鼠分别接受1.5毫克/千克腹腔注射的氯化镉、30毫克/千克口服单次剂量的氯化镉,以及连续7天每天4.28毫克/千克分次剂量口服的氯化镉。在所有接触镉的动物中均观察到镉的生物蓄积。仅在分次口服途径中,肝脏中的钙和铁浓度升高。仅口服单次剂量时,肝脏中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性增加。在所有口服给药形式中,谷胱甘肽S-转移酶(GST)均下降,而丙二醛(MDA)仅在腹腔注射途径中下降。腹腔注射途径中肝脏重量和肝脏指数增加,而在所有口服给药形式中器官体积增加,并且在所有接触镉的动物中肝脏密度增加。在肝脏组织形态计量学方面,口服给药时变化更明显,主要是在单次接触金属时。因此,镉以不同给药途径进行亚急性给药会导致肝脏中毒出现不同变化。

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