Alterations of Cholesterol Lowering-Related Proteins in the Serum of Hypercholesterolemic-Induced Rats Treated with Ficus deltoidea
SAINS MALAYSIANA
Authors: Ham, Chuo Peck; Uzar, Fatima; Abdul-Rahman, Puteri Shafinaz; Abdullah, Noorlidah; Aminudin, Norhaniza
Abstract
Cardiovascular disease (CVD) is one of the major non-communicable diseases causing cardiac dysfunction and heart failure. In Malaysia, hypercholesterolemia or high blood cholesterol is known as CVD's main risk factor. Currently, there is a paradigm shift of interest in Eastern medicines as alternative prevention approaches and therapeutic cholesterol control treatment. Ficus deltoidea (Mas Cotek) is amongst the eastern medicinal plants traditionally consumed either as prevention or treatment for various diseases such as hypertension, diabetes and hypercholesterolemia. This study utilised the proteomic application in determining the changes in a series of proteins that are being differentially expressed in response to F. deltoidea treatment ofhypercholesterolemic-induced rats. Identification and quantification of proteins were conducted by using quantitative techniques, wherein two dimensional gel electrophoresis (2D-GE) along with Progenesis Samespots image analysis software and Matrix-assisted laser desorption/ionization Time-of-flight/Time-of-flight (MALDI ToF/ToF) mass spectrometry were utilised. Our results demonstrated that 14 protein spots had displayed alteration in their abundance at a minimum of 1.5 fold. Majority of these identified proteins were involved in lipid metabolism and immune system processes. These variables include apolipoprotein A1 (Apo A1), apolipoprotein E (Apo E), retinol binding protein 4 (RBP4), haptoglobin (HP), complement factor C3 (C3), complement factor C1s (C1s), fransthyretin (TTR), ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3), prominin 1 (PROM1) and plasminogen (PLG). Serum proteome analysis has unravelled the understanding on the mechanism of cholesterol reducing by F. deltoidea via augmentation of cholesterol biosynthesis that enhanced bile acids excretion, causing lowered cholesterol absorption in hypercholesterolemic rats.
Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with Lu-177-octreotate
EJNMMI RESEARCH
Authors: Dalmo, Johanna; Westberg, Emelie; Barregard, Lars; Svedbom, Lisa; Johansson, Martin; Tornqvist, Margareta; Forssell-Aronsson, Eva
Abstract
Background: The kidneys are regarded as one of the main dose-limiting organs in the treatment of neuroendocrine tumours with Lu-177-[DOTA(0), Tyr(3)]-octreotate (Lu-177-octreotate), despite the successful use of kidney uptake blocking agents such as lysine and arginine. To avoid renal toxicity but still give each patient as high amount of Lu-177-octreotate as possible, there is a need for methods/biomarkers that indicate renal injury in an early stage of the treatment. The aim of this study was to investigate the potential of using urinary retinol binding protein 4 (RBP4) and carbamoylated haemoglobin (Hb) in blood as biomarkers of nephrotoxic effects on adult mice after Lu-177-octreotate treatment. Methods: Adult BALB/c nude mice were injected with 60 MBq or 120 MBq of Lu-177-octreotate or with saline (control). Urine was collected before injection and concentrations of urinary RBP4 and creatinine were determined 14 to 90 days after injection Blood samples were collected after 90 days, and carbamoylated N-terminal valine in Hb, formed from urea, was measured as valine hydantoin (VH) after detachment from Hb. Results: The RBP4 values increased with administered activity and time. For the 60 and 120 MBq groups, statistically significantly higher RBP4 levels (p <0.05) were found at day 60 and 90 compared to baseline, also at day 30 for 120 MBq group. For VH, the mean values were similar for the 60 MBq and control groups, while a small increase was observed for the 120 MBq group; but there were no statistically significant differences between any of the groups (p >0.05). No morphological changes in the kidney tissue were found. Conclusions: Urinary RBP4 is a promising new biomarker for radiation-induced renal toxicity. For the conditions used in this experiment, carbamoylated Hb (from urea) measured as VH may not be a sufficiently sensitive biomarker to be used for renal toxicity.