The low calorie natural sweetener stevioside: Nephrotoxicity and its relationship to urinary enzyme excretion in the rat

The relationships between urinary enzyme levels and changes in blood urea nitrogen (BUN) and plasma creatinine levels, along with simultaneous ultrastructural changes of the kidney, were studied in rats treated with stevioside. BUN levels increased at 3 h onward after subcutaneous injection (s.c.) with stevioside (1.5 g/kg BW). The maximum increases in BUN and creatinine were approximately 180% and 132% at 9 h after stevioside injection, respectively. At this time, stevioside also caused significant increases in glucosuria, alkaline phosphatase (AP) and γ-glutamyl transpeptidase (γ-GTP) but no significant changes in proteinuria, N-acetyl-β-D-glucuronidase (NAG) or glutathione-S-transferase (GSH-S-TF). Histopathological examination of the kidney induced by stevioside revealed degeneration of the proximal convoluted tubule cells but no relation to lipid peroxide formation was detected. These results suggest that stevioside induced nephrotoxicity at the proximal convoluted tubules rather than at the glomeruli and other tubules presumably by a defect of cell volume regulation due to depletion of intracellular ATP and disruption of microvilli, and nuclear dysfunction.     

Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids

Background  

Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity. A variety of studies have tried to find MDR modulators which increase drug accumulation in cancer cells.