Effects of Antioxidant Supplementation on Duodenal Se-Met Absorption in Ethanol-exposed Rat Offspring In Vivo

Abstract

Abstract. The nutritional deficiencies provoked by ethanol consumption, during gestation or lactation, can contribute to multiple birth defects in offspring. In order to improve our knowledge about selenium (Se) distribution in pups exposed to ethanol, the present study evaluated the effect of this drug on intestinal development and determined its action on duodenal absorption of selenomethionine (Se-Met). To determinate if supplementation could improve Se absorption and its serum values, we used two antioxidant supplemented regimens on dams, with selenium alone or selenium plus folic acid, and obtained six groups of pups: C (control), A (alcohol), CS (control + Se), AS (alcohol + Se), CFS (control + Se + folic acid) and AFS (alcohol + Se + folic acid). Duodenal Se-Met transport was performed using an in vivo perfusion method. Se levels were measured by graphite furnace atomic absorption spectrometry. The supplemented diets utilized had a positive influence on body growth, duodenal perimeter and Se content in ethanol-exposed pups. Ethanol exposure increased Se-Met duodenal absorption in all pups, supplemented or not, presenting the highest values of maximal velocity (V max ) compared with their control counterparts. The affinity constant (K m ) increased according to rank: A>AS>AFS groups. These results suggest that although antioxidant supplementation does not restore Se-Met absorption to normal values, it enhances the affinity of the transporters for the substrate and improves the damage caused by ethanol in the duodenal mucosa.Key words: Ethanol, Kinetic parameters, Offspring development, Selenomethionine absorption (J. Reprod. Dev. 57: [708][709][710][711][712][713][714] 2011) T he primary function of the intestinal epithelium is to absorb the small molecules produced from food digestion [1]. However, specific substances such as alcohol could alter this intestinal absorption [2,3], producing malnutrition. Numerous studies have demonstrated that chronic ethanol consumption induces morphological and biochemical alterations in the intestinal mucosal cells [4] and that some of these changes are caused by a lipid peroxidation of duodenal membrane lipids [5]. These effects of ethanol exposure are more acute during pregnancy and lactation and can contribute to a delay in offspring growth and multiple birth defects, including fetal alcohol syndrome [6]. In this context, it is especially relevant that ethanol deregulates the homeostasis of different antioxidants such as folic acid, whose deficiency is the most common sign of malnutrition in chronic alcoholism [7]. This deficiency is associated with several alterations such as Down's syndrome and defects in neural tube closure in developing embryos [1]. According to what we have previously reported [8], the effects of ethanol exposure during gestation and lactation on folic acid intestinal absorption showed that intestinal folate absorption appears to be upregulated in suckling rats. Our research group has also found, in pups exposed to ethanol and supplemented wit...

The role of folic acid and selenium against oxidative damage from ethanol in early life programming: a review

“…It could be concluded that dietary Se supplementation to dams mitigated the adverse effects of alcohol in ethanol-exposed offspring (Ojeda et al 2009a;Ojeda et al 2010a;Nogales et al 2011), increasing the expression of GPx1, GPx4 and SelP P (Jotty et al 2013), thus confirming Se therapy as an exogenous supplementation with a real antioxidant capacity and biological D r a f t function, being especially important after ethanol consumption and during gestation and breastfeeding -the early stages of pups' lives.…”

“…Despite this corporal redistribution of maternal Se deposits, milk Se levels were lower in ethanol-exposed dams (Jotty et al 2013). Moreover, weaning pups intake less milk and ethanol alters their intestinal absorption decreasing the pups' intestinal perimeter, as well as its length and weight (Nogales et al 2011, Bhalla et al 2004, even affecting the Se-methionine D r a f t transport system. Finally, at the end of lactation, the surviving pups presented a high retardation in their development together with a deficient Se intake.…”

“…Therefore, in order to avoid future oxidative damage to them and their progeny, a controlled supplementary Se antioxidant therapy would appear to be recommendable for mothers who consume ethanol during gestation and lactation. In this context different studies have analyzed with different objectives the effects of Se supplementation (0.5ppm of sodium selenite) upon both ethanol-exposed dams during gestation and lactation and their offspring in order to improve their oxidative balance (Ojeda et al 2009b;Ojeda et al 2009c;Ojeda et al 2012); to analyze their intestinal Se-Met absorption (Nogales et al 2011); to evaluate Se absorption, retention and body distribution (Jotty et al 2009;Ojeda et al 2010a, Ojeda et al 210b), and to study selenoprotein liver expression (Jotty et al 2013). These studies confirm that Se supplementations improve the transporter's affinity to substrates needed for Se-methionine absorption and minimize the ethanol-induced damage in the duodenal mucosa, improving Se bioavailability in pups and even improving their nutritional status (Nogales et al 2011).…”

Fetal Programming Is Deeply Related to Maternal Selenium Status and Oxidative Balance; Experimental Offspring Health Repercussions

“…Additionally, to worsen the relationship among EtOH exposure and Se homeostasis, EtOH-exposed weaning pups intake less milk and have lower intestinal perimeters, presenting a down-regulation in the SelMet transport system [ 157 , 158 ]. This lead to a greater Se homeostasis disruption, more than in dams [ 159 ], which mainly compromised Se deposits in liver, kidney and heart.…”

“…In order to reinforce the hypothesis that EtOH-exposure during preconception, gestation and lactation periods affects the oxidative profile and Se homeostasis in the progeny, which is in part related to their metabolic future health, in our laboratory, dietary Se antioxidant supplementation (0.5 ppm of sodium selenite) was given to EtOH–exposed Wistar dams. With this model, we pursued different objectives: to analyze the reproductive parameters and the intestinal SelMet absorption process in weaning pups [ 158 ], to evaluate Se retention and body distribution in dams and their offspring [ 155 , 159 , 184 ], to improve fetal and lactating pups hepatic oxidative balance, in part related to gestational and breastfeeding parameters [ 7 , 154 , 160 , 166 ], and to study selenoprotein liver expression and their possible biological role in weaning pups [ 156 ]. The narrow window between therapeutic and toxic doses of Se, as well as the dependence of its effect on the applied form, dose and method of treatment, makes the choice of an effective supplement a very complex issue.…”