title: Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a single exposure to low and moderate doses of cadmium in rats.
abstract: Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis.
authors.affiliation: Department of Animal Biology, Federal University of Viçosa, Viçosa, MG, Brazil; Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
authors.forename: Marli C
authors.initials: MC
authors.lastname: Cupertino
authors.forename: Kyvia L C
authors.initials: KL
authors.lastname: Costa
authors.forename: Daiane C M
authors.initials: DC
authors.lastname: Santos
authors.forename: Rômulo D
authors.initials: RD
authors.lastname: Novaes
authors.forename: Suellen S
authors.initials: SS
authors.lastname: Condessa
authors.forename: Ana C
authors.initials: AC
authors.lastname: Neves
authors.forename: Juraci A
authors.initials: JA
authors.lastname: Oliveira
authors.forename: Sérgio L P
authors.initials: SL
authors.lastname: Matta
mesh_terms: D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000453:epidemiology / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006706:Homeostasis / Q000187:drug effects; D015994:Incidence; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009336:Necrosis / Q000453:epidemiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D002104:Cadmium; D003094:Collagen; D002374:Catalase; D013482:Superoxide Dismutase
keywords: fibrosis; heavy metal; hepatic injury; oxidative stress; toxicology
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