Alpha-tocopherol prevents intrauterine undernutrition-induced oligonephronia in rats

Abstract

The role of α-tocopherol during nephrogenesis was investigated in rats subjected to maternal undernutrition, which reduces the number of nephrons. α-tocopherol (350 mg/kg, p.o.) was administered daily to well-nourished or malnourished Wistar dams during pregnancy, or to prenatal undernourished rats during lactation. The kidneys of 1- and 25-day-old offspring were removed to evaluate expression of angiotensin II (Ang II) and to correlate this with expression of proliferating cell nuclear antigen, α-smooth muscle actin, fibronectin and vimentin in the glomeruli and tubulointerstitial space. One-day-old prenatally undernourished rats had reduced expression of Ang II and of kidney development markers, and presented with an enlarged nephrogenic zone. Maternal administration of α-tocopherol restored the features of normal kidney development in undernourished rats. Twenty-five-day-old prenatally undernourished progeny had fewer glomeruli than the control group. Conversely, animals from mothers that received α-tocopherol during lactation presented with the same number of glomeruli and the same glomerular morphometrical profile as the control group. Analyzing the levels of thiobarbituric acid reactive substances in the liver in conjunction with kidney development markers, it is plausible that α-tocopherol had antioxidant and non-antioxidant actions. This study provides evidence that α-tocopherol treatment restored Ang II expression, and subsequently restored renal structural development.

How the Kidney Is Impacted by the Perinatal Maternal Environment to Develop Hypertension1

“…Blockade of the RAS during the postnatal period of the rat that corresponds to nephrogenesis programs hypertension in the adult rat that is reduced by treatment with tempol [122]. An increase in renal markers of oxidative stress are also observed in different animal models of developmental insult [106,108,[116][117][118], including adult offspring exposed to prenatal undernutrition [79,80], placental insufficiency [84], or models that involve suppression of the RAS during early life [8,71,83,123]. Importantly, increased oxidative stress is linked to an elevation in blood pressure in the male rat relative to the female rat [119,122,124], suggesting that oxidative stress may contribute to the sexual dimorphic control of blood pressure and cardiovascular risk induced by a prenatal insult.…”

“…Maternal treatment with the antioxidant a-tocopherol during lactation in prenatally undernourished rats [123] or cross-fostering pups at birth of placental insufficient dams [73] prevents oligonephronia. Oligonephronia induced by maternal undernutrition is also prevented by administration of ouabain in parallel with maternal undernutrition during pregnancy.…”

Perinatal Na+ Overload Programs Raised Renal Proximal Na+ Transport and Enalapril-Sensitive Alterations of Ang II Signaling Pathways during Adulthood

“…The surface density of collagen and ED1 was identified by a researcher and counted using the Image Pro Plus 4.5.1 software (Media Cybernetics, Bethesda, MD). Immunostaining for Ang II in renal cortical cells was carried out as previously described [31] in slices prepared and incubated with the corresponding antibody (1∶200). The results in the graphic representations of collagen and ED1 correspond to the ratio between positive areas and the total area under observation.…”

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

“…Several pathogenic mechanisms involved in renal programming, as we discussed above, can be the target for early intervention. Previous studies indicate that early treatment with α-tocopherol [116], quabain (an inhibitor of NaKATPase) [117], or retinoid acid [118] ameliorates reductions in nephron endowment in different programming models. We recently reviewed a numbers of reprogramming interventions that have been directed at restoring the balance of NO and ROS [15].…”