Prenatal and early postnatal food restrictions cause changes in brain oxidative status and orexigenic/anorexigenic hormones in the offspring of rats: prevention by quercetin and kaempferol

Abstract

Brain oxidative signaling pathways have been identified as important targets for alleviating food deprivation-induced changes in metabolic gate-ways. Previous studies have shown that prenatal and early postnatal malnutrition alters leptin and ghrelin signaling via oxidative pathways. Thus, it has been hypothesized that agents with antioxidant properties might be beneficial for the mitigation of prenatal and early postnatal food scarcity-induced oxidative damage. Quercetin and kaempferol are natural bioflavonoids with proven antioxidant properties. In this study, we evaluated their effects on prenatal maternal food consumption, maternal and pup weights, biomarkers of orexigenic and anorexigenic hormones and oxidative stress in rats. Rats were allotted into different treatment groups (n ​= ​6) in three different experiments (prenatal, postnatal food-deprivations or both). Prenatal-food restriction (PrNFR) was induced by 50% of ad libitum accessible diet during pregnancy till parturition and postnatal-food restriction (PsNFR) was simulated by litter-enlargement to 16 pups per mother from postnatal day (PND) 2. Rats in each experiment were concurrently treated with vehicle (10 ​mL/kg), quercetin (50, 100 and 200 ​mg/kg, p.o.) or kaempferol (50, 100 and 200 ​mg/kg, p.o.) respectively. A third experimental group consisted of both protocols. Quercetin and kaempferol dose-dependently increased the body weights of pups exposed to PrNFR, PsNFR and PrNFR-PsNFR at PNDs 1–22 respectively. Both compounds increased maternal body weights but attenuated maternal food-intake at prenatal days 7 and 14 due by PrNFR. Quercetin and kaempferol reduced brain malondialdehyde concentrations and increased glutathione levels in PrNFR, PsNFR and PrNFR-PsNFR-exposed offspring of rats. Importantly, quercetin and kaempferol significantly ( p ​< ​0.05) prevented PrNFR-, PsNFR- or PrNFR-PsNFR-induced alterations in leptin and ghrelin levels. Cumulatively, quercetin and kaempferol increased pup and maternal weights and attenuated maternal food-intake of rats submitted to PrNFR, PsNFR and PrNFR-PsNFR respectively, likely via nutrigenomic modulations of orexigenic/anorexigenic hormones and inhibition of brain oxidative stress.

Promising bioactive properties of quercetin for potential food applications and health benefits: A review

“…Compared to quercetin in its free form, derivatives of quercetin appear to have stronger bone-protective properties ( 49 ). In estrogen deficiency-induced bone loss and ovariectomized rats, quercetin and kaempferol prominently advance bone mineralization, bone microstructure, and osteoblast activity ( 50 ). Table 3 includes different health benefits of quercetin.…”

“…Quercetin and kaempferol have been shown in numerous papers to attenuate various metabolic syndromes linked to prenatal and early postnatal stress through pathways involving suppression of oxidative stress and inflammatory process in entire animals and cultured human endothelia cells. Overall, the research by Anachuna et al ( 50 ) acknowledged potential links between prenatal and early postnatal food limitations, altered orexigenic/anorexigenic hormone levels in the serum, and elevated brain oxidative stress in Wistar rats, which is reversible by antioxidant therapies. The effects of prenatal, postnatal, or combination food shortages on rats' pup weights were found to be enhanced by quercetin and kaempferol through mechanisms including the modulation of leptin and ghrelin levels including antioxidant pathways.…”

“…The effects of prenatal, postnatal, or combination food shortages on rats' pup weights were found to be enhanced by quercetin and kaempferol through mechanisms including the modulation of leptin and ghrelin levels including antioxidant pathways. In order to combat alterations in metabolic and brain functioning brought on by prenatal and early postnatal dietary shortage, quercetin and kaempferol supplementation may be essential ( 50 ).…”

Evidence for Quercetin as a Dietary Supplement for the Treatment of Cardio-Metabolic Diseases in Pregnancy: A Review in Rodent Models

“…Once perinatal protein restriction increases the concentration of free radicals and inflammatory cytokines, experimental evidence investigates the administration of antioxidant and anti-inflammatory bioactive compounds on the phenotypic plasticity of malnourished animals in early life [ 10 , 54 , 55 ]. Among these compounds, quercetin stands out due to its antiobesity, anti-inflammatory, antioxidant and antidyslipidemic functions, which may contribute to regulating body weight, biochemical, and metabolism parameters [ 56 ].…”

“…One mechanism explaining these results was that quercetin increased leptin (anorexigenic hormone) and reduced ghrelin expression (orexigenic hormone), reducing eating and increasing energy expenditure. Furthermore, the study showed that quercetin mitigated perinatal malnutrition-induced oxidative stress in the rat brain by increasing glutathione (GSH) concentrations [ 54 ].…”