Abstract
Recently, studies have shown that renal dysfunction is associated not only with overt diabetes but also with the preceding stage known as prediabetes. Diet and pharmacological interventions are the therapeutic approaches to managing prediabetes, but the compliance in combining the two interventions is low. Hence, the efficacy of pharmacological intervention is reduced without diet modification. In our previous study, we established that bredemolic acid (BA) ameliorated glucose homeostasis via increased GLUT 4 expression in the skeletal muscle of prediabetic rats in the absence of diet intervention. However, the effects of bredemolic acid on renal function in prediabetic condition are unknown. Therefore, this study was aimed at investigating the ameliorative effects of bredemolic acid on renal dysfunction in a diet-induced prediabetic rat model. Thirty-six Sprague-Dawley male rats (150–180 g) were divided into two groups: the nonprediabetic (n = 6) and prediabetic (n = 30) groups which were fed normal diet (ND) and high-fat high-carbohydrate (HFHC) diet, respectively, for 20 weeks. After the 20th week, the prediabetic groups were subdivided into prediabetic control (PD) and 4 other prediabetic groups which were treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) for further 12 weeks (21st to 32nd). Plasma, urine, and kidney samples were collected for biochemical analysis. The untreated prediabetic (PD) rats presented increased fluid intake and urine output; increased creatinine, urea, and uric acid plasma concentrations; albuminuria; proteinuria; sodium retention; potassium loss; increased aldosterone and kidney injury molecule (KIM-1) concentration; and increased urinary podocin mRNA expression. However, BA administration attenuated the renal markers and oxidative stress and decreased the urinary podocin mRNA expression. In conclusion, BA administration, regardless of diet modification, attenuates renal dysfunction in an experimentally induced prediabetic state.
Highlights
More than 25% of type 1 and type 2 diabetes mellitus patients have been reported to develop renal dysfunction [1, 2]
Renal dysfunction is defined by the appearance of abnormal kidney functional changes such as a reduced glomerular filtration rate (GFR), increased serum creatinine and urea, albuminuria, increased excretion of kidney injury molecule (KIM-1), and glomerular podocyte injury with urinary loss of podocin
High-fat or high-fructose diet has been associated with impaired glucose metabolism and insulin resistance which in turn leads to metabolic disturbances with complications that result in renal dysfunction such as decreased plasma concentration of albumin and total protein, albuminuria, proteinuria, and diffuse thickening of the glomerular capillary basement membrane [30,31,32,33]
Summary
More than 25% of type 1 and type 2 diabetes mellitus patients have been reported to develop renal dysfunction [1, 2]. The renal dysfunction does occur in overt diabetes and in the early stages of impaired glucose metabolism [3, 4]. Renal dysfunction is defined by the appearance of abnormal kidney functional changes such as a reduced glomerular filtration rate (GFR), increased serum creatinine and urea, albuminuria, increased excretion of kidney injury molecule (KIM-1), and glomerular podocyte injury with urinary loss of podocin. Literature evidence showed that about one-third of individuals with newly diagnosed diabetes mellitus have varying degrees of renal dysfunction [15]. This can only be attributed to the abnormal changes that occur during prediabetes. Antidiabetic agents that can possibly ameliorate CKD regardless of diet intervention are considered necessary
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