Queiroz 2024 Ecotoxicol Environ Saf
| Queiroz MIC, Lazaro CM, Dos Santos LMB, Rentz T, Virgilio-da-Silva JV, Moraes-Vieira PMM, Cunha FAS, Santos JCC, Vercesi AE, Leite ACR, Oliveira HCF (2024) In vivo chronic exposure to inorganic mercury worsens hypercholesterolemia, oxidative stress and atherosclerosis in the LDL receptor knockout mice. Ecotoxicol Environ Saf 275:116254. https://doi.org/10.1016/j.ecoenv.2024.116254 |
Queiroz Maiara IC, Lazaro Carolina M, Dos Santos Lohanna MB, Rentz Thiago, Virgilio-da-Silva Joao V, Moraes-Vieira Pedro MM, Cunha Francisco AS, Santos Josue CC, Vercesi Anibal E, Leite Ana Catarina R, Oliveira Helena CF (2024) Ecotoxicol Environ Saf
Abstract: Heavy metal exposure leads to multiple system dysfunctions. The mechanisms are likely multifactorial and involve inflammation and oxidative stress. The aim of this study was to evaluate markers and risk factors for atherosclerosis in the LDL receptor knockout mouse model chronically exposed to inorganic mercury (Hg) in the drinking water. Results revealed that Hg exposed mice present increased plasma levels of cholesterol, without alterations in glucose. As a major source and target of oxidants, we evaluated mitochondrial function. We found that liver mitochondria from Hg treated mice show worse respiratory control, lower oxidative phosphorylation efficiency and increased H2O2 release. In addition, Hg induced mitochondrial membrane permeability transition. Erythrocytes from Hg treated mice showed a 50% reduction in their ability to take up oxygen, lower levels of reduced glutathione (GSH) and of antioxidant enzymes (SOD, catalase and GPx). The Hg treatment disturbed immune system cells counting and function. While lymphocytes were reduced, monocytes, eosinophils and neutrophils were increased. Peritoneal macrophages from Hg treated mice showed increased phagocytic activity. Hg exposed mice tissues present metal impregnation and parenchymal architecture alterations. In agreement, increased systemic markers of liver and kidney dysfunction were observed. Plasma, liver and kidney oxidative damage indicators (MDA and carbonyl) were increased while GSH and thiol groups were diminished by Hg exposure. Importantly, atherosclerotic lesion size in the aorta root of Hg exposed mice were larger than in controls. In conclusion, in vivo chronic exposure to Hg worsens the hypercholesterolemia, impairs mitochondrial bioenergetics and redox function, alters immune cells profile and function, causes several tissues oxidative damage and accelerates atherosclerosis development. • Keywords: Atherosclerosis, Hypercholesterolemia, Macrophage, Mercury toxicity, Mitochondria, Oxidative stress • Bioblast editor: Plangger M • O2k-Network Lab: BR Campinas Vercesi AE
Labels: MiParea: Respiration, Genetic knockout;overexpression
Pathology: Other
Organism: Mouse Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ET
Pathway: N
HRR: Oxygraph-2k
2024-04
