The Induced Oxidative DNA Damage and Presenillin-1 Mutations by the Pharmacologically Used NaCl Saline Solutions Increase the Incidence of Alzheimer Disease in Mice
Keywords:
presenillin 1, oxidative DNA damage, Alzheimer disease, NaCl and mice.Abstract
The addition of sodium chloride (NaCl) to food by the manufacturer or consumer and its medical use particularly as a drug dilution solvent result in elevated concentrations of sodium and chloride ions in human blood and tissues, including the brain. However, all previous studies were concerned on its induced renal toxicity and no attention on its neurotoxicity, thus the current study investigated the saline induced genotoxicity, mutagenicity and oxidative stress in mice brain tissue. Mice were administered 0.9, 3, or 5% saline solution by intraperitoneal injection (10 mL/kg body weight) every two days for a total of 6 injections and euthanized 24 h after the last injection. Multiple injections of NaCl saline solutions induced DNA damage in neurons and elicited a high incidence of presenillin-1 mutations and ?-amyloid accumulation in a dose-dependent manner. These outcomes could be attributed to the observed elevations in serum cholesterol levels and increased generation of reactive oxygen species, indicated by the elevated malondialdehyde and nitric oxide levels and reduced glutathione levels and catalase activity in NaCl-treated groups. We conclude that multiple injections of NaCl solution, even at the concentration of normal saline (0.9%), caused cholesterol accumulation and oxidative DNA damage that resulting in mutations in presenillin-1 and also increased ?-amyloid accumulation in the brain therapy increasing the incidence of Alzheimer disease in a dose-dependent manner in mice. Therefore, its recommended to reduce the uses of saline in drug dilutions.
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