# Isoflavone Protects the Renal Tissue of Diabetic Ovariectomized Rats via PPARy
## 1 Introduction  
Type 1 diabetes (T1D) has high rates of morbidity and mortality and an increasing incidence. From the moment of diagnosis, the management of diabetes mellitus (DM) places an enormous burden on the patient, with severe limitations, changes in lifestyle, and organ dysfunction [1]. Diabetic nephropathy (DN) is one of the leading causes of kidney disease worldwide, and being in the post-menopause stages of life contributes to a worse prognosis [2, 3, 4], as postmenopausal sex hormone levels affect the renal/vascular physiology [5].  
Estrogen prevents the development and progression of kidney disease and improves postmenopausal symptoms, especially in diabetes, the main risk factor for chronic kidneydisease. In addition, women with lower endogenous exposure to estrogen have a higher risk of kidney disease [6]. Isoflavone is known for its estrogenic role [7]. The beneficial effect of isoflavone has been demonstrated in an animal model of diabetes [8] and in humans [9]. The ingestion of soy protein, total isoflavone, daidzein, and genistein is associated with lower risks of DM2 in a dose-dependent manner in women, though this effect is not evident in men [9]. These observations may be population-dependent, as in a cross-section of North American subjects, isoflavone was shown to be effective for men and women with DM2 [10]. Nevertheless, few studies have demonstrated the effect of isoflavone on T1D, especially in renal injury [11; 12].  
Peroxisome proliferator-activated receptor gamma (PPAR\(\gamma\)) has been closely associated with diabetes, menopause, and kidney disease. Due to its role in glucose regulation, PPAR\(\gamma\) agonists are suggested to ameliorate the problems of diabetes [13]. Our group demonstrated that isoflavone positively regulates PPAR\(\gamma\). In addition, work from the lab demonstrated beneficial effects on diabetic conditions and in obese animals [12; 13; 14]. We previously demonstrated that isoflavone protects from kidney injury in obese animals via PPAR-\(\gamma\)[14], prevents bone loss in ovariectomized diabetic animals [15], and can attenuate the effects of vulvovaginal atrophy in women [16]. Taking into account the protective function of PPAR-\(\gamma\) in kidney injury [17; 18; 19; 20], the objective of this work was to evaluate the effect of ovariectomy and the consequent gonadal failure on the development of DM1-induced kidney injury, as well as the contribution of soy isoflavone via PPAR-\(\gamma\) in this experimental animal model. Our hypothesis is that gonadal failure potentiates renal injury induced by chronic hyperglycemia and that isoflavone treatment attenuates this condition by PPAR-\(\gamma\) induction.  
Our data revealed that isoflavone protects the kidney against gonadal failure associated with DM1 damage. Increased protein and gene expression of PPAR-\(\gamma\) was evidenced under the influence of isoflavone. In addition, we demonstrate for the first time that PPAR-\(\gamma\) reduction occurs dose-dependent on glucose. On the other hand, we have not clearly demonstrated the consequences of ovariectomy in the renal injury development, and other findings are necessary to confirm this hypothesis.