7-cloro-4-(fenilselanil)quinolina reduz o dano oxidativo induzido pela oxaliplatina em fígado e rim de ratos envelhecidos

Abstract

Brazil and the world are aging. The rate of people over 60 years of age has grown more and more in recent times, and the aging process has been indicated as a risk factor for several diseases, such as cancer. In this context, it is worth mentioning that colorectal cancer is the third in incidence in the elderly. One of the chemotherapy drugs recommended for the treatment of colorectal cancer is oxalipatin (OXA). However, several studies reveal the toxic effects of OXA to the body, among them the oxidative damage to various tissues and systems, such as liver and kidney. In view of this, molecules with antioxidant potential may represent a promising alternative for the treatment of damage caused by OXA in aged individuals. Thus, this study aimed to evaluate the pharmacological potential of 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) against hepatic and renal toxicity induced by OXA in aged rats. For this, old rats (20 months) received the administration of OXA (10 mg/kg, intraperitonally, i.p) or vehicle on days 0 and 2 of the experimental protocol. In addition, the animals were treated with 4-PSQ (1 mg/kg, intragastric, i.g.) or vehicle, from days 2 to 14 of the experimental protocol. Twenty-four hours after the last treatment, the animals were euthanized. Blood, liver and kidney samples were collected to determine markers of liver and kidney damage and oxidative stress. Effects of 4-PSQ treatment were evaluated through changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, urea levels, in the plasma of the animals, as well as oxidative stress markers in the liver and kidney of aged rats (thiobarbituric acid reactive species (TBARS), non-protein thiol (NPSH); enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), delta-aminolevulinate dehydratase (δ-ALA-D)), and renal activity of the enzyme Na+,K+-ATPase. The weight of the animals was verified at the beginning and at the end of the experimental protocol. Results indicate that aging causes a greater loss of body mass, which can be aggravated by the administration of OXA. OXA caused renal and hepatic damage in aged rats, evidenced by increased levels of urea and transaminase activities (AST and ALT) in plasma. Furthermore, oxidative stress parameters were altered by aging and exacerbated by OXA administration. Treatment with 4-PSQ reduced plasma urea levels and AST and ALT activities, reducing OXA induced liver and kidney damage in aged animals. Furthermore, 4-PSQ treatment reduced lipid oxidation and restored antioxidant enzymes homeostasis in aged rats disturbed by OXA administration. In conclusion, the results indicate that 4-PSQ may be a good therapeutic strategy to attenuate OXA-induced tissue damage in the elderly.