生化学と薬理学: オープンアクセス
オープンアクセス

概要

Lithium Toxicity Effects on Oxidative Stress, Dyslipidemia and Apoptosis in the Aged Rats

Katiucha KHR Rocha, Rodrigo P Ureshino, Janaína Peixoto, Fernanda Mani and Soraya S Smaili

Aging is associated with metabolic changes and the development of diseases, due to the reduction of antioxidant defenses and alteration in apoptosis process. The lithium is used to treat bipolar disorder and neuroprotector; it also can be used as an antioxidant, but its function in aging has not been elucidated. The alterations in apoptosis could be associated with development oxidative stress in several tissues, although this information is unclear to aged rats. Disorders in apoptosis process and/or oxidative stress development impair the health of aged rats. The association between apoptosis with hepatic metabolism changes and oxidative stress disorder in aging is also unclear. Therefore, the objective of this work was to determine the effects of lithium on the lipid profile in serum and oxidative stress as well as apoptosis in the liver of aged rats. Twenty female Wistar rats were divided into 4 groups (n=5): the C group, with 3- month-old rats that received only water; the L group, with 3- month-old rats that received a lithium solution in drinking water; the S group, with 22- month-old rats that received water; and the SL group, with 22- month-old rats that received lithium in drinking water. The total experimental period was 30 days. All animals received standard diet ad libitum. The lithium dose took was according to neuroprotective dose and carefully monitored daily. The dyslipidemia studies were made through TC, HDL, LDL, VLDL, TG and glucose in serum. Oxidative stress analyses involved experiments with LH, TAS and ATP-SA. The apoptotic proteins analyses were made by western blot. Oxidative stress and apoptotic proteins were studied in the liver rats. The results showed that the lithium treatment reduced energy intake, aqueous solution intake and palatability in both, young and aged rats. This treatment increased TG and VLDL in the serum of animals in both groups. The treatment promoted hyperglycemia in young group, and in aged group, induced LDL enhanced as well as decreased HDL. Lithium induced enhanced Sirt 1 in livers of young and aged rats. TAS were higher in young group submitted lithium treatment. The livers of aged rats supplemented with lithium exhibited raised ATP- SA and Bax. In conclusion, the lithium induced dyslipidemia and hyperglycemia in the young, but this treatment also acted as a possible antioxidant agent, associated with Sirt 1 enhanced to protect this tissue of damages. In the aged rats, lithium promoted dyslipidemia and could induce cell death. Therefore, the supplementation could exert toxic effects in the livers of aged rats.