RESUMEN
OBJECTIVE: Tert-butylhydroquinone (t-BHQ) protective effect against oxidative damage in thymus from malnourished pops-rats was evaluated. METHODS: Malnutrition in pops-rats was induced during the lactation period and first-, second-, and third-degree malnourished rats were studied (MN1, MN2, and MN3). To determine t-BHQ protective effect, lipid peroxidation (LPx) was assessed, as well as the carbonyl content. The reduced glutathione and glutathione disulfide content were determined and antioxidant enzyme activities were measured. RESULTS: Oxidative protein damage, LPx, and Nuclear Factor-κB (NF-κB) content, increased in the MN2 and MN3 compared to well-nourished rats, associated with lower protein content and antioxidant activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase. Tert-butylhydroquinone treatment induced a protective effect against lipids and proteins oxidative damage, as well as decrease in NF-κB in MN rats and restored the antioxidant mechanisms, mostly GPx and SOD. No differences were found between male and female animals. CONCLUSIONS: Results show that higher body weight deficit leads to increased oxidative damage and probably inflammation, attributable to alterations in antioxidant mechanisms. These effects were reversed by the t-BHQ-treatment, which restores the antioxidant response. Our findings suggest that t-BHQ could be an interesting pharmacological intervention, but it needs to be studied further.
RESUMEN
OBJECTIVE: Malnutrition has been associated with oxidative damage by altered antioxidant protection mechanisms. Specifically, the aim of this study was to evaluate oxidative damage (DNA and lipid) and antioxidant status (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] mRNA, and protein expression) in thymus from malnourished rat pups. METHODS: Malnutrition was induced during the lactation period by the food competition method. Oxidative DNA damage was determined quantifying 8-oxo-7, 8-dihydro-2'-deoxyguanosine adduct by high-performance liquid chromatography. Lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances. Levels of gene and protein expression of SOD, GPx, and CAT were evaluated by real-time polymerase chain reaction and Western blot, respectively. Antioxidant enzyme activities were measured spectrophotometrically. RESULTS: Oxidative DNA damage and lipid peroxidation significantly increased in second-degree (MN-2) and third-degree malnourished (MN-3) rats compared with well-nourished rats. Higher amounts of oxidative damage, lower mRNA expression, and lower relative concentrations of protein, as well as decreased antioxidant activity of SOD, GPx, and CAT were associated with the MN-2 and MN-3 groups. CONCLUSIONS: The results of this study demonstrated that higher body-weight deficits were related to alterations in antioxidant protection, which contribute to increased levels of damage in the thymus. To our knowledge, this study demonstrated for the first time that early in life, malnutrition leads to increased DNA and lipid oxidative damage, attributable to damaged antioxidant mechanisms including transcriptional and enzymatic activity alterations. These findings may contribute to the elucidation of the causes of previously reported thymus dysfunction, and might explain partially why children and adults who have overcome child undernourishment experience immunologic deficiencies.