Renoprotective mechanisms of soy protein intake in the obese Zucker rat

Abstract

We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO 2 and NO 3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-␤, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-␤1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-␤1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-␤ expression. oxidative stress; nitric oxide; endothelial nitric oxide synthase phosphorylation; short leptin receptor

Dietary isoflavones and vascular protection: Activation of cellular antioxidant defenses by SERMs or hormesis?

“…Notably, feeding an isoflavone enriched diet to rats for only 4-6 months has marginal benefits for endothelial function (Douglas et al, 2006), suggesting that isoflavone supplements may only affect endothelial function in aged animals with existing CVD (Trujillo et al, 2005(Trujillo et al, , 2008. Consistent with the reported vasodilatory actions of genistein and dehydroequol in humans (Walker et al, 2001;Chin-Dusting et al, 2004), we have shown that isoflavones evoke rapid endothelium-dependent and -independent relaxation of preconstricted arterial rings (Joy et al, 2006).…”

RETRACTED ARTICLE: Soy protein prevents renal damage in a fructose-induced model of metabolic syndrome via inhibition of NF-kB in male rats

“…Enhanced ROS formation during hyperglycemia could be one factor for elevation in TGF-β1, since antioxidants inhibit glucose-induced upregulation of TGF-β1 [33]. Significant reduction in TGF-β1 expression by soy protein has been shown in another model of IR [34].…”

Proinflammatory gene expression and renal lipogenesis are modulated by dietary protein content in obese Zuckerfa/farats

“…There is abundant experimental evidence, and to a lesser degree, clinical evidence, demonstrating that the amount and type of dietary protein may influence kidney function (11,12,33,39,47,49). Despite some controversy, there is a generalized belief that low-protein diets are beneficial in the treatment of patients with CKD and can reduce the progression of kidney disease (3,33,39).…”

“…On the other hand, it has been claimed that vegetable protein is beneficial for individuals with CKD as it can help improve renal blood flow perfusion and reduce inflammation (12). Indeed, vegetable proteins like soy protein increase the production of nitric oxide, promoting normal renal function in obese rats (49). Additionally, soy protein preserves glomerular filtration rate in rats with chronic renal failure in clear association with the lower production of metabolic acid evaluated by the urine net acid excretion and kidney acid content (57).…”