Background. Prediabetes is an intermediary hyperglycaemic state that precedes type 2 diabetes mellitus (T2DM) in which abnormal metabolism of glucose and lipids occurs in organs such as the liver. Evidence has shown that, about 70% of T2DM patients develop hepatic dysfunction which is found to begin during the prediabetic stage. Bredemolic acid, a pentacyclic triterpene, has been found to improve insulin sensitivity in diet-induced prediabetic rats. The effects of this compound on liver function, however, are unknown. This study was therefore designed to investigate the effects of BA on liver function in high fat-high carbohydrate (HFHC) diet-induced prediabetic rats. Methods. Thirty-six (36) male rats that weigh 150 g–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 30) that were fed normal diet (ND) and HFHC diet, respectively. The prediabetic rats were further subdivided into five groups (n = 6) and treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) every third day for 12 weeks. After 12 weeks, blood samples and the liver were collected for biochemical analysis. Results. The induction of prediabetes resulted in increased release of liver enzymes (AST and ALT), increased liver glycogen and triglyceride, lipid peroxidation, and decreased sterol regulatory element-binding protein (SREBP1c) and antioxidant enzymes. However, the administration of BA decreased liver enzyme concentrations, decreased hepatic oxidative stress, and improved antioxidant enzymes such as SOD and GPx. Conclusion. BA administration improved liver function in diet-induced prediabetic rats in the presence or absence of dietary intervention.

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 20^th 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 (21^st to 32^nd). 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.

Non-alcoholic fatty liver disease (NAFLD) is associated with prediabetes and can be treated by using a combination of metformin and dietary modification. However, people often fail to adhere to dietary modifications and become more dependent on pharmaceutical intervention, and this affects the effectiveness of the drug. In this study, we investigated the effects of rhenium (V) compound with uracil-derived ligands on liver health in diet-induced prediabetic rats in both the presence and absence of dietary modification. Prediabetic male Sprague Dawley rats were treated with the rhenium (V) compound for 12 weeks in both the presence and absence of dietary modification while monitoring fasting blood glucose levels. Antioxidant enzyme activity, inflammation markers and liver enzymes were measured together with liver glycogen and plasma triglycerides after sacrificing. The administration of rhenium (V) compound to prediabetic rats in both the presence and absence of dietary modification resulted in reduced concentrations of fasting blood glucose and triglycerides. There was also reduced liver glycogen, oxidative stress and liver enzymes while increasing antioxidant enzymes. Altogether, the rhenium (V) compound ameliorated liver injury and prevented hepatotoxicity.

Kidney disease is characterised by the improper functioning of the kidney as a result of kidney damage caused by hyperglycaemia-induced oxidative stress. The moderate hyperglycaemia seen in prediabetes can be treated using a combination of metformin and lifestyle interventions (low-calorie diets and exercising). However, patients have been reported to over-rely on pharmacological interventions, thus decreasing the efficacy of metformin, which leads to the development of type 2 diabetes mellitus (T2DM). In this study, we investigated the effects of a rhenium (V) compound in ameliorating renal dysfunction in both the presence and absence of dietary modification. Kidney function parameters, such as fluid intake and urine output, glomerular filtration rate (GFR), kidney injury molecule (KIM 1), creatinine, urea, albumin and electrolytes, were measured after 12 weeks of treatment. After treatment with the rhenium (V) compound, kidney function was restored, as evidenced by increased GRF and reduced KIM 1, podocin and aldosterone. The rhenium (V) compound ameliorated kidney function by preventing hyperglycaemia-induced oxidative stress in the kidney in both the presence and absence of dietary modification.

Prediabetes is an intermediate hyperglycaemic state which has been associated with cardiovascular dysfunction. However, cardiovascular dysfunction is not only caused by intermediate hyperglycaemia but also endothelial dysfunction, inflammation, and oxidative stress associated with prediabetes. Bredemolic acid (BA), an isomer of maslinic acid, has been reported to ameliorate the intermediate hyperglycaemia found in prediabetes; however, the effects of this triterpene on cardiovascular function have not yet been determined. Therefore, this study investigated the effects of BA on cardiovascular function in diet-induced prediabetic rats. Thirty-six male rats that weighed 150–180 g were divided into two groups, the non-prediabetic (n = 6) and the prediabetic groups (n = 30), which were fed normal diet (ND) and HFHC diet, respectively. The prediabetic rats were further subdivided into five groups (n = 6) and treated with either BA (80 mg/kg) or metformin (MET, 500 mg/kg) every third day for 12 weeks. After 12 weeks, blood samples and the heart were collected for biochemical analysis. The untreated prediabetic rats showed a significant increase in body mass index (BMI), waist circumference (WC), blood pressure, heart rate, lipid profile, lipid peroxidation, and inflammatory markers with significant decrease in endothelial function and antioxidant biomarkers by comparison with the non-prediabetic animals. The administration of BA significantly improved cardiovascular functions such as blood pressure, heart rate, and endothelial function. There was also a significant decrease in BMI, WC, lipid profile, lipid peroxidation, and inflammation with a concomitant increase in antioxidant capacity. BA administration improved cardiovascular function by attenuation of oxidative stress, inflammatory, and endothelial dysfunction markers.