Dieta hipercalórica suplementada com espermidina: estudo dos efeitos sobre lesões induzidas no DNA

Abstract

DNA damage marks the onset of the carcinogenesis process, which, if uncontrolled, can lead to disease progression. Diets rich in processed and ultra-processed foods, high in calories and sugar, are associated with the development of various chronic noncommunicable diseases (NCDs), including cancer. Conversely, preventive measures, such as a healthy diet rich in bioactive compounds, are crucial for reducing the risk of DNA damage and promoting longevity. Spermidine (SPD) is a bioactive polyamine that induces autophagy, has anti-inflammatory, immunomodulatory, and antioxidant properties, and has the potential to inhibit cell proliferation. The present study evaluated the effects of SPD supplementation in rodents fed a high-calorie diet (HD) rich in sucrose, before and after the induction of DNA lesions. The study used male Swiss mice, fed HD [standard diet (SD) + 30% sucrose diluted in water], and/or supplemented with 10 and 30 mg/kg body weight (bw) of SPD for 44 days. Peripheral blood samples were collected at 48 hours and 44 days for monitoring mutagenicity. On day 44, the mutagenic agent methyl methanesulfonate [MMS 40 mg/kg bw intraperitoneally (ip)] was administered to induce mutagenicity, and after 24 hours, bone marrow and liver cells were collected to evaluate the protective effect using micronucleus and comet assays, respectively, and to investigate the endogenous antioxidant potential. The results showed that HD significantly reduced feed intake and increased water consumption. None of the treatments demonstrated cytotoxicity and mutagenicity. Animals treated with SPD 30 mg/kg bw combined with MMS in SD (SPD 30 mg/kg bw + MMS) and HD (SPD 30 mg/kg + MMS + HD) showed a reduction in the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow and DNA damage in hepatocytes. Supplementation with SPD 10 and 30 mg/kg bw, combined with MMS in animals fed SD and HD, significantly increased CAT levels in the liver, whereas this behavior was not observed for SOD. Therefore, the chemopreventive and antioxidant effects of SPD 30 mg/kg bw treatment were shown to be more promising when associated with SD, considered balanced. These evaluations collectively contribute to elucidating the chemopreventive effect of SPD and suggest that further studies should be conducted to investigate the mechanism involved in this activity