Hepatocellular carcinoma (HCC) is a lethal complication in the human liver. The most important problems with HCC are that the tumor appears in several areas of the liver, it is difficult to diagnose and identify, and there is a possibility of tumor recurrence (1). Therefore, identification of diagnostic biomarkers of HCC and effective therapeutic agents is very necessary. Organic cation transporters are integral transmembrane factors with critical effects in metabolism and detoxification via uptake of endogenous and exogenous elements and anticancer drugs. Organic cation transporter 3 (OCT3), as a transporting protein in human, can remove small organic cations created by environmental toxins and/or drugs (2)....

Organic cation transporter 3 (OCT3) as a high-capacity transporter contribute to the metabolism of metformin. The present study was conducted to determine the genotype frequencies of the variant OCT3-1233G>A (rs2292334) in patients with newly diagnosed type 2 diabetes (T2D) and its relationship with response to metformin. Materials and Methods: This study included 150 patients with T2D who were classified into two groups following three months of metformin therapy: responders (by more than 1% reduction in HbA1c from baseline) and nonresponders (less than 1% reduction in HbA1c from baseline). PCR-based restriction fragment length polymorphism (RFLP) served to genotype OCT3-564G>A variant. Results: The parameters such as HbA1c (P<0. 001) and BMI (P<0. 001) in both patients with GA + AA genotype and GG genotype decreased significantly following 3 months of metformin therapy compared with baseline. The mean reduction in HbA1c levels following 3 months was higher in patients with the A allele (0. 77% reduction from baseline) than in those with the homozygous G allele (0. 54% reduction from baseline). Also, in GA + AA genotypes compared with GG genotypes, the mean reduction in HbA1c values from baseline was 0. 34% for responders and 0. 14% for non-responders. Conclusion: Considering the roles of genetic variations in the function of metformin transporters, the effect of variations such as 1233G>A in the OCT3, which is a high-capacity transporter widely expressed in various tissues cannot be ignored. Comparing the allele frequencies of OCT3-1233G>A variant in our study and different ethnic populations confirm that the variant is a highly polymorphic variant.

Introduction: Cisplatin induced nephrotoxicity may limit the clinical use of this drug. The aim of this study was to investigate the mechanism of the possible renoprotective effect of curcumin in cisplatin nephrotoxicity. Methods: Thirty male Wistar rats were randomly divided into five groups: 1-control (0. 5ml normal saline ip, daily for 10 constitutive days); 2-cisplatin (10mg/kg ip, single dose at the first day); 3-cisplatin + curcumin (10mg/kg ip, dissolved in 5% DMSO, daily for 10 constitutive days); 4-cisplatin + vehicle (5% DMSO, 0. 3ml ip) and 5-curcumin (10mg/kg ip). At the end of the study, urine and blood samples were obtained for biochemical (BUN, creatinine, sodium and potassium) analysis. The right kidneys were kept in 10% formalin for H&E and TUNEL staining, and the left kidneys were used for type 2 organic cation transporter (OCT2) and type 3 glutathione peroxidase (GPx3) gene expression and malondialdehyde measurements. Results: Cisplatin significantly increased serum creatinine, BUN, potassium and kidney lipid peroxidation. However, the effect of cisplatin on Gpx3 and OCT2 gene expression was not statistically significant. Curcumin treatment decreased serum creatinine, BUN, and kidney lipid peroxidation, but increased GPx3 and OCT2 gene expression. Moreover, curcumin significantly reversed the cisplatin-induced kidney tissue injury and decreased apoptosis. Conclusion: It is concluded that the ameliorative effect of curcumin in cisplatin nephrotoxicity was assumed to be due to antioxidant effect of this agent. The role of curcumin in mediating uptake of cisplatin is still unclear.

Background: Organic cation transporter 3 (OCT3) is an excellent transporter for metformin, which is used as first-line therapy for type 2 diabetes (T2D). OCT3 genetic variants may influence the clinical response to metformin. This study aimed to determine the genotype and allele frequency of OCT3-564G>A (rs3088442) variant and its role in the glycemic response to metformin in patients with newly diagnosed T2D. Materials and Methods: Based on the response to metformin, 150 patients were classified into two groups: Sixty-nine responders (decrease in glycated hemoglobin [HbA1c] values by more than 1% from the baseline) and 81 nonresponders (decrease in HbA1c values<1% from the baseline). HbA1c levels were determined by chromatography. The variant OCT3-564G>A was genotyped using polymerase chain reaction - based restriction fragment length polymorphism.Results: The genotypes frequencies were 51.3% GG, 36% AG, and 12.7% AA. Allele frequency of major allele (G) and minor allele (A) in OCT3-564G>A variant was found to be 0.69 and 0.31, respectively. Fasting glucose, HbA1c, body mass index, and lipid profile in both GG genotypes and GA+AA group decreased significantly after 3 months of metformin therapy compared with baseline (P<0.05). In both responders and nonresponders, HbA1c and fasting glucose levels were lower in patients with the GA+AA genotype than in those with the GG genotype; however, the differences were not statistically significant (P>0.05).Conclusion: The A allele frequency (which may be a protective allele against coronary heart disease) in the Iranian diabetic patients was lower than Iranian, Caucasian and Japanese healthy populations. Metformin is useful in improving the lipid profile, in addition to its impacts in glycemic control, and these effects are regardless of OCT3-564G>A variant.

Transport studies have been carried out across a newly synthesized inorganic–organic nanocomposite membrane. Membrane potential measurements have been measured in various monovalent electrolyte environments at different concentrations to analyse the relationship between transport properties and fixed charge concentration of the membrane. The charge densities were found to follow the order K+ >Na+ >Li+. The counter-ion transport number, ionic mobility ratio and permselectivity of the nanocomposite membrane have also been calculated which reveal that the inorganic–organic nanocomposite membrane shows a higher selectivity towards K+ ions; however, the selectivity decreases with decrease in dilution for all monovalent electrolytes tested. These membranes were comprehensively characterized for their physicochemical properties, morphology, molecular interactions and crystallinity by sophisticated techniques. The ionexchange capacity, volume void porosity and water uptake of the membrane were found to depend on the polystyrene content in the membrane phase and these properties decreased with increase in the amount of polymer (15–35 % by mass). Moreover, membrane containing 25 % of polystyrene exhibited good selectivity along with moderate ion-exchange capacity, which may be used for their application in electro-driven separation at high temperatures or for other electrochemical processes.