title: Inactivation of Kupffer Cells by Selenizing Astragalus Polysaccharides Prevents CCl4-Induced Hepatocellular Necrosis in the Male Wistar Rat.
abstract: Selenizing astragalus polysaccharides-3 (sAPS3) was prepared by nitric acid-sodium selenite method. The effects of sAPS3on carbon tetrachloride (CCl4) induced hepatocellular necrosis, and its underlying mechanisms were studied in male Wistar rats. Hepatic damage was induced by intraperitoneal injection of CCl4twice a week, for 3 weeks. Meanwhile, the rats in addition to CCl4were also exposed to sodium selenite (SS), astragalus polysaccharides (APS), SS + APS or sAPS3, in parallel by oral gavage once a day for 3 weeks. At the end of 3 weeks, blood and liver tissue were taken. Serum was collected to test the levels of alanine aminotransferase, aspartate aminotransferase and antioxidant status parameters. Liver tissue was collected for histopathological examination and determination of messenger RNA (mRNA) expression levels of CD68, TNF-α, IL-1β and ATG7 followed by the measurements of CD68, IL-1β and LC3II by immunohistochemistry assay (IHC), or TNF-α by immunofluorescence assay (IFA). The results showed that sAPS3effectively ameliorated CCl4induced hepatocellular necrosis and inflammation and significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde and the expression levels of Kupffer cells (KCs)-specific biomarker CD68 and proinflammatory cytokines produced by activated KCs such as IL-1β and TNF-α (P < 0.01). While increasing the levels of total antioxidant capacity, glutathione, glutathione peroxidase and superoxide dismutase (P < 0.05) and reduced the expression levels of a key regulator of autophagy in KCs ATG7 or LC3II (P < 0.05). These findings indicate that sAPS3could ameliorate CCl4-induced hepatocellular necrosis by inactivation of Kupffer cells and its activity may be superior to the application of selenium, APS or combination of selenium with APS.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing, 210095, China.|College of Veterinary Sciences, University of Nyala, Nyala, Sudan.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hamid
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing, 210095, China.|College of Veterinary Sciences, University of Nyala, Nyala, Sudan.
authors.forename: Yassin
authors.initials: Y
authors.lastname: Abdulrahim
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Alamzeb
authors.initials: A
authors.lastname: Khan
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing, 210095, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Qian
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China. khhuang@njau.edu.cn.|Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowl, Nanjing Agricultural University, Nanjing, 210095, China. khhuang@njau.edu.cn.
authors.forename: Kehe
authors.initials: K
authors.lastname: Huang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D027885:Astragalus propinquus / Q000737:chemistry*; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002251:Carbon Tetrachloride; D016207:Cytokines; D004798:Enzymes; D005978:Glutathione; D008315:Malondialdehyde; D011134:Polysaccharides; D012643:Selenium; C539355:CD68 protein, rat; D000097382:CD68 Molecule
keywords: CCl4; Hepatocellular necrosis; Inflammation; Rats; Selenizing astragalus polysaccharides