2,4-二氯苯氧乙酸对幼龄SD大鼠肝毒性的研究

doi:10.3969/j.issn.1004-616x.2021.01.005

Abstract

Abstract: OBJECTIVE: To investigate the hepatotoxicity of 2, 4dichlorophenoxyacetic acid in young SD rats. METHODS: 64 young SD rats with SPF grade were randomly divided into three 2, 4-D inoculation groups (18.125, 36.250, 72.500 mg/kg) and a solvent control group (1% carboxymethyl cellulose). The rats were inoculated with the chemicals orally once a day for 28 days. After the exposure, their general behavior and weight changes were monitored, wet weights and viscera coefficients of the livers were calculated. Pathology of the livers were determined after their staining with hematoxylin-Eosin (HE). Activities of glutathione (GSH), total superoxide dismutase (T-SOD) and concentrations of malondialdehyde (MDA) were measured using the DTNB assay, and xanthine oxidase and TBA assays were conducted after liver samples were pretreated. Contents of cytochrome C, relative activities of Caspase-3 and Caspase-9 in liver tissues were determined by spectrophotometer. RESULTS: Compared with the control group, rats from the 72.500 mg/kg treatment group showed the following:body weight gains and liver wet weight were reduced significantly (P < 0.05);parts of the livers had bile duct hyperplasia which were accompanied with inflammatory cell infiltration;GSH activities in the liver homogenates were decreased (P < 0.05);and MDA concentrations were increased (P < 0.05). In rats from both the 36.250 mg/kg and 72.500 mg/kg treatment groups, the activities of TSOD were decreased (P < 0.05); cytochrome C concentrations were increased (P < 0.05); and the relative activities of caspase-3 and caspase-9 were increased (P < 0.05). CONCLUSION: Under the conditions of this investigation, 2, 4-D was shown to induce hepatotoxicity in young SD rats. The toxicity was probably mediated by changing mitochondrial membrane permeability and releasing apoptotic factor to induce hepatocyte apoptosis, thereby causing oxidative damage to hepatocytes.

Key words: 2,4-dichlorophenoxyacetic acid, hepatotoxicity, apoptosis, oxidative damage

CLC Number:

R994.6

HUANG Lili, ZHANG Mengyun, LIU Keliang, PANG Dingguo, LIU Lida, XU Peiyu. Hepatotoxicity of 2,4-dichlorophenoxyacetic acid in young SD rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 22-27.

References

[1] NAKBI A, TAYEB W, GRISSA A, et al. Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats[J]. Nutr Metab, 2010, 7:80.
[2] PANNU A K, SAROCH A, AGRAWAL J, et al. 2,4-D poisoning:a review with illustration of two cases[J]. Trop Doct, 2018, 48(4):366-368.
[3] FREITAS L M, VALADARES L A, CAMOZZI M, et al. Animal models in the neurotoxicology of 2,4-D[J]. Hum Exp Toxicol, 2019, 38(10):1178-1182.
[4] 苟练, 张梦云, 刘科亮, 等. 2,4-二氯苯氧乙酸对初断乳SD大鼠生殖器官发育的影响及相关机制[J]. 癌变·畸变·突变, 2018, 30(5):389-394.
[5] TU P, GAO B, CHI L, et al. Subchronic low-dose 2,4-D exposure changed plasma acylcarnitine levels and induced gut microbiome perturbations in mice[J]. Sci Rep, 2019, 9(1):4363.
[6] TAYEB W, NAKBI A, TRABELSI M, et al. Biochemical and histological evaluation of kidney damage after sub-acute exposure to 2,4-dichlorophenoxyacetic herbicide in rats:involvement of oxidative stress[J]. Toxicol Mech Method, 2012, 22(9):696-704.
[7] SALVO L M, MALUCELLI M I, DA S J, et al. Toxicity assessment of 2,4-D and MCPA herbicides in primary culture of fish hepatic cells[J]. J Environ Sci Health B, 2015, 50(7):449-455.
[8] BUENO FRANCO SALLA G, BRACHT L, VALDERRAMA PARIZOTTO A, et al. Kinetics of the metabolic effects, distribution spaces and lipid-bilayer affinities of the organochlorinated herbicides 2,4-D and picloram in the liver[J]. Toxicol Lett, 2019, 313:137-149.
[9] KAIOUMOVA D, SÜSAL C, OPELZ G. Induction of apoptosis in human lymphocytes by the herbicide 2,4-dichlorophenoxyacetic acid[J]. Hum Immunol, 2001, 62(1):64-74.
[10] TUSCHL H, SCHWAB C. Cytotoxic effects of the herbicide 2, 4dichlorophenoxyacetic acid in HepG2 cells[J]. Food Chem Toxicol, 2003, 41(3):385-393.
[11] TAYEB W, NAKBI A, TRABELSI M, et al. Hepatotoxicity induced by sub-acute exposure of rats to 2,4-Dichlorophenoxyacetic acid based herbicide"Désormone lourd"[J]. J Hazard Mater, 2010, 180(1/2/3):225-233.
[12] CHARLES J M, CUNNY H C, WILSON R D, et al. Comparative subchronic studies on 2,4-Dichlorophenoxyacetic acid, amine, and ester in rats[J]. Fundam Appl Toxicol, 1996, 33:161-165.
[13] KERR J F, WYLLIE A H, CURRIE A R. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J]. Brit J Cancer, 1972, 26(4):239-257.
[14] 张玉静, 蒋妮, 柳强, 等. 线粒体损伤在镉诱导肝细胞凋亡和DNA损伤中的作用[J]. 卫生研究, 2020, 49(2):290-297.
[15] SUN Q, ZHONG W, ZHANG W, et al. Zinc deficiency mediates alcoholinduced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways[J]. Am J Physiol Gastrointest Liver Physiol, 2015, 308:G757-G766.
[16] CELAJ S, GLEESON M W, DENG J, et al. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury[J]. Lab Invest, 2014, 94(9):938-949.
[17] 郝涛, 田浩明. 利拉鲁肽对非酒精性脂肪性肝炎C57小鼠肝细胞凋亡及Bcl-2/Bax, Caspase-9表达的影响[J]. 四川医学, 2020, 41(3):271-275.
[18] WEN X, WU J, WANG F, et al. Deconvoluting the role of reactive oxygen species and autophagy in human diseases[J]. Free Radical Bio Med, 2013, 65:402-410.
[19] AZZI A. Oxidative stress:A dead end or a laboratory hypothesis?[J]. Biochem Bioph Res Co, 2007, 362(2):230-232.
[20] WU T, BAI H, ZHAO Z, et al. A prospective study on associations between superoxide dismutase gene polymorphisms and antituberculosis drug-induced liver injury in a Chinese Han population[J]. J Gene Med, 2019, 21(10):e3121
[21] LU S C. Dysregulation of glutathione synthesis in liver disease[J]. Liver Res, 2020, 4(2):64-73.
[22] 马武仁, 卿颖, 李子琪, 等. 食品中典型持久性有机污染物暴露及毒性通路研究进展[J]. 中华预防医学杂志, 2019(6):645-652.

Hepatotoxicity of 2,4-dichlorophenoxyacetic acid in young SD rats

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	GUO Ruixian, XIE Guangyun, HAN Ying. Injury effects of gatifloxacin in livers of mice based on transcriptome sequencing [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 20-24.
[2]	LI Boru, QIN Shuangjian, GUAN Lan, LI Runbing, CAI Ying, PU Jiening, ZENG Ming, XIAO Fang, XU Xinyun. Effects of PM_2.5 on oxidative damage and apoptosis in HK-2 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(5): 360-364.
[3]	HUANG Xiaohua, NIU Yongdong, SHI Ganggang. Inhibitory effects and mechanisms of nuclear receptor FXR activation in cervical cancer cell line CaSki [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 302-306.
[4]	WANG Xikai, MENG Qinghe, GAO Yanlu. miR-223-3p negatively regulated ECT2 to induce apoptosis in non-small cell lung cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 187-192.
[5]	CHEN Tingyu, CHEN Dayin, XIE Jinlu, GAO Xiren, LU Chunfeng. Role of the Nrf2/ARE signaling pathway on quercetin-inhibition of INH-induced mitochondrial oxidative damage in hepatocytes [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 208-212,217.
[6]	LI Boru, QIN Shuangjian, LI Runbing, CAI Ying, ZHENG Kai, ZENG Ming, XIAO Fang, XU Xinyun. Effects of p38MAPK gene on PM_2.5-induced expression of oncogenes and apoptosis genes in HK-2 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 129-135,142.
[7]	MA Shunpeng, WANG Quankai, WANG Miao, SONG Jiayang, WUHAN Baolier, XIE Guangyun, XU Jianning. Long non-coding RNA regulates apoptosis during glycidyl methacrylate-induced malignant transformation of 16HBE cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 1-5,31.
[8]	LI Boru, QIN Shuangjian, LI Runbing, CAI Ying, ZHENG Kai, WANG Bingyu, ZENG Ming, XIAO Fang, XU Xinyun. Effects of PM_2.5 exposure on expression of oncogenes and apoptosis genes in human renal epithelial cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 6-11.
[9]	CHEN Tingyu, CHEN Dayin, SHEN Hong, FU Xuyan, LU Chunfeng. Protective effects of quercetin on isoniazid-induced hepatotoxicity in vitro [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 12-16.
[10]	CUI Zhaoyang, LI Suna, JIANG Xuqian, WANG Yidan, HOU Liying. Activation of the TRAIL death receptor by apigenin for induction of apoptosis in the gastric cancer SGC-7901 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 32-36.
[11]	LAN Li, CHEN Haili, XU Lei. Mechanism of RBMS3-S3 on the proliferation, apoptosis and invasion of cervical cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 438-443.
[12]	LIU Peng, BAI Yixiao. Effect of miR-29a on proliferation and migration of human gastric cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 452-456,463.
[13]	YANG Xingxiao, ZHANG Xueyuan, ZOU Naiyi, SHAN Bao'en, MA Ming, ZHU Shuchai. Effect of HMGB1 silencing by siRNA on radiosensitivity of esophageal carcinoma KYSE30 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 269-274.
[14]	QIN Shuangjian, LI Boru, CAI Ying, ZHENG Kai, WANG Bingyu, LI Runbing, XIAO Fang, ZENG Ming, XU Xinyun. PM_2.5 exposure on expression of oncogenes and apoptosis genes in hepatocytes [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 281-285.
[15]	CAI Ying, ZHENG Kai, QIN Shuangjian, LI Boru, YU Shuyuan, LIU Ning, JI Jiajia, ZHANG Zhaohui, XU Xinyun. Silencing of c-fos gene on expression of oncogenes and apoptosis genes in HBE cells exposed to PM_2.5 [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 298-303,308.