title: Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway.
abstract: Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue.
authors: Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China. longjlau@126.com.|College of Life Engineering, Shenyang Institute of Technology, Fushun 113122, China. longjlau@126.com.
authors: Miao
authors: M
authors: Long
authors: School of Chemical Engineering, Sichuan University of Science and Engineering, Zigong 643000, China. liuyi0961@sina.com.
authors: Yi
authors: Y
authors: Liu
authors: Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China. m15648566678@163.com.|College of Life Engineering, Shenyang Institute of Technology, Fushun 113122, China. m15648566678@163.com.
authors: Yu
authors: Y
authors: Cao
authors: Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China. wn168168wn@163.com.|College of Life Engineering, Shenyang Institute of Technology, Fushun 113122, China. wn168168wn@163.com.
authors: Nan
authors: N
authors: Wang
authors: Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China. joydivisiondang@sina.com.|College of Life Engineering, Shenyang Institute of Technology, Fushun 113122, China. joydivisiondang@sina.com.
authors: Meng
authors: M
authors: Dang
authors: Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China. hejianbin69@163.com.
authors: Jianbin
authors: J
authors: He
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D006360:Heat-Shock Proteins / Q000378:metabolism; D007854:Lead / Q000009:adverse effects* / Q000097:blood; D007855:Lead Poisoning / Q000188:drug therapy / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008815:Mice, Inbred Strains; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D000975:Antioxidants; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D044945:Proanthocyanidins; D019253:Proto-Oncogene Proteins c-bcl-2; D051742:Transcription Factor CHOP; D007854:Lead
keywords: ER stress; Nrf2/ARE pathway; apoptosis; lead; liver; mice; oxidative damage; proanthocyanidin