scholarly journals EFFECTS OF CURCUMIN AND NANOCURCUMIN ON CISPLATIN-INDUCED NEPHROTOXICITY IN RAT: COPPER TRANSPORTER 1 AND ORGANIC CATION TRANSPORTER 2 AS DRUG TRANSPORTERS

2018 ◽  
Vol 10 (1) ◽  
pp. 172
Author(s):  
Deliana Nur Ihsani Rahmi ◽  
Melva Louisa ◽  
Vivian Soetikno
Keyword(s):  
Single Dose ◽  
Organic Cation ◽  
Rat Kidney ◽  
Kidney Tissue ◽  
Organic Cation Transporter ◽  
Copper Transporter ◽  
Renal Tubular Cells ◽  
Organic Cation Transporter 2 ◽  
Renal Tubular ◽  
Copper Transporter 1

Objective: This study aimed to investigate the efficacy of curcumin (CMN) and nanocurcumin (NC) at preventing cisplatin (CDPP)-inducednephrotoxicity.Methods: Two membrane transporters, copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2), have been identified involved in activeaccumulation of CDPP into renal tubular cells. We analyzed OCT2 transcription levels in rat kidney tissue and determined whether renoprotectivemechanism of CMN involves CTR1. Rats were randomly divided into five groups: (1) Control, (2) CDPP (7 mg/kg as single dose (i.p.), (3) CDPP+CMN(7 mg/kg CDPP as a single dose, i.p.+100 mg/kg/day of CMN), (4) CDPP+50 mg NC (7 mg/kg CDPP as single dose, i.p.+50 mg/kg/day NC), and(5) CDPP+100 mg NC (7 mg/kg CDPP as single dose, i.p.+100 mg/kg/day NC). Quantitative reverse transcription-polymerase chain reaction wasperformed to calculate relative expression of CTR1 and OCT2 genes in rat kidney.Results: Expression of CTR1 was unassociated with administration of CMN or NC, indicating CTR1 is uninvolved in renoprotective mechanism of CMN.The administration of 100 mg/kg/day NC increased expression of OCT2; this increase was higher compared with normal expression levels. This maybe due to another regulatory mechanism from the CMN itself.Conclusion: NC has a better renoprotective effect compared with curcumin, suggested by the increased OCT2 expression on its administration inCDPP-treated rats.

scholarly journals Impact of Expression Levels of Platinum-uptake Transporters Copper Transporter 1 and Organic Cation Transporter 2 on Resistance to Anthracycline/Taxane-based Chemotherapy in Triple-negative Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S27534
Author(s):  
Risa Takeda ◽  
Ayano Naka ◽  
Naoki Ogane ◽  
Yoichi Kameda ◽  
Kae Kawachi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Platinum Drugs ◽  
Ki 67 ◽  
Copper Transporter ◽  
Organic Cation Transporter 2 ◽  
Uptake Transporters ◽  
Copper Transporter 1

Adding platinum drugs to anthracycline/taxane (ANC-Tax)-based neoadjuvant chemotherapy (NAC) improves pathological complete response (pCR) rates in triple-negative breast cancer (TNBC). Copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2) critically affect the uptake and cytotoxicity of platinum drugs. We immunohistochemically determined CTR1 and OCT2 levels in pre-chemotherapy biopsies from 105 patients with HER2-negative breast cancer treated with ANC-Tax-based NAC. In the TNBC group, Ki-67high [pathological good response (pGR), P = 0.04] was associated with response, whereas CTR1high (non-pGR, P = 0.03), OCT2high (non-pGR, P = 0.01; non-pCR, P = 0.03), and combined CTR1high and/or OCT2high (non-pGR, P = 0.005; non-pCR, P = 0.003) were associated with non-response. In multivariate analysis, Ki-67high was an independent factor for pGR and CTR1 for non-pGR. Combined CTR1/OCT2 was a strong independent factor for non-pGR. However, no variables were associated with response in luminal BC. These results indicate that platinum uptake transporters are predominantly expressed in ANC-Tax-resistant TNBCs, which implies that advantage associated with adding platinum drugs may depend on high drug uptake.

Relevance of copper transporter 1 and organic cation transporters 1–3 for oxaliplatin uptake and drug resistance in colorectal cancer cells

Metallomics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 414-425 ◽  
Author(s):  
I. Buß ◽  
A. Hamacher ◽  
N. Sarin ◽  
M. U. Kassack ◽  
G. V. Kalayda
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporters ◽  
Copper Transporter ◽  
Colorectal Cancer Cells ◽  
Organic Cation Transporter 2 ◽  
Organic Cation Transporter 1 ◽  
Copper Transporter 1

Copper transporter 1 and organic cation transporter 2 mediate oxaliplatin uptake in sensitive and resistant colorectal cancer cells. Organic cation transporter 1 is involved in oxaliplatin uptake only in sensitive cells underscoring its relevance for oxaliplatin resistance.

scholarly journals O32 Ontogeny of human kidney OCT2 expression across the paediatric age range

2019 ◽  
Vol 104 (6) ◽  
pp. e14.2-e14
Author(s):  
N Smeets ◽  
B van Groen ◽  
J Pertijs ◽  
M Wilmer ◽  
B Smeets ◽  
...  
Keyword(s):  
Organic Cation ◽  
Basolateral Membrane ◽  
Age Groups ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Organic Cation Transporter ◽  
Age Related ◽  
Paediatric Age ◽  
Organic Cation Transporter 2 ◽  
Related Pattern

BackgroundIn adults, the organic cation transporter 2 (protein name OCT2, gene name SLC22A2) is localised in the kidney proximal tubules where it mediates organic cation secretion. Hence, the transporter plays a role in the disposition and excretion of several drugs and drug-drug interactions. To better understand the disposition of OCT2 substrate drugs in children, we studied OCT2 localisation and expression in paediatric kidney tissue.MethodsThe expression of OCT2 was visualised in tissue using immunohistochemical staining. Tissues were derived post-mortem from children aged 0 -14 years. Gestational age varied between 24 and 40 weeks. Intensity of the staining at the basolateral membrane was scored by two individual observers using three categories; negative, detectible and high. Agreement between two observers was determined using Cohen’s kappa.Results44 kidney samples (n=17 neonates, n=17 infants, n=7 children, n=3 adolescent) were analysed and scored. There was substantial agreement between two judgements with a kappa of 0.773 (p< 0.005). No age related pattern was observed in the expression of OCT2. Even in the youngest age group, the expression of OCT2 was clearly visible.ConclusionThe kidney expression of OCT2 did not show an age-related pattern. In all age groups, expression levels were similar and OCT2 was properly localised at the basolateral membrane. These findings suggest that, with increasing age, OCT2 will not influence the renal excretion of its substrates.Disclosure(s)Nothing to disclose

scholarly journals The Role of NF-kB in the Downregulation of Organic Cation Transporter 2 Expression and Renal Cation Secretion in Kidney Disease

2022 ◽  
Vol 8 ◽  
Author(s):  
Chao Han ◽  
Juan Zheng ◽  
Fengyi Wang ◽  
Qingyang Lu ◽  
Qingfa Chen ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Organic Cation ◽  
Rat Kidney ◽  
Basolateral Membrane ◽  
Kidney Injury ◽  
Organic Cation Transporter ◽  
Tubular Secretion ◽  
Gene Reporter Assay ◽  
Organic Cation Transporter 2

Organic cation transporter 2 (OCT2), encoded by the SLC22A2 gene, is the main cation transporter on the basolateral membrane of proximal tubular cells. OCT2 facilitates the entry step of the vectorial transport of most cations from the peritubular space into the urine. OCT2 downregulation in kidney disease models is apparent, yet not clear from a mechanistic vantage point. The aim of this study was to explore the role of inflammation, a common thread in kidney disease, and NF-kB in OCT2 modulation and tubular secretion. Among the OCTs, OCT2 was found consistently downregulated in the kidney of rats with chronic kidney disease (CKD) or acute kidney injury (AKI) and in patients diagnosed with CKD, and it was associated with the upregulation of TNFα renal expression. Exposure to TNFα reduced the expression and function of OCT2 in primary renal proximal tubule epithelial cells (RPTEC). Silencing or pharmacological inhibition of NF-kB rescued the expression of OCT2 in the presence of TNFα, indicating that OCT2 repression was NF-kB-dependent. In silico prediction coupled to gene reporter assay demonstrated the presence of at least one functional NF-kB cis-element upstream the transcription starting site of the SLC22A2 gene. Acute inflammation triggered by lipopolysaccharide injection induced TNFα expression and the downregulation of OCT2 in rat kidney. The inflammation did reduce the active secretion of the cation Rhodamine 123, with no impairment of the glomerular filtration. In conclusion, the NF-kB pathway plays a major role in the transcriptional regulation of OCT2 and, in turn, in the overall renal secretory capacity.

Ultrastructural changes in the rat kidney after single dose of cyclophosphamide—Possible roles for peroxisome proliferation and lysosomal dysfunction in cyclophosphamide-induced renal damage

2011 ◽  
Vol 30 (12) ◽  
pp. 1924-1930 ◽  
Author(s):  
Premila Abraham ◽  
Bina Isaac
Keyword(s):  
Electron Microscopy ◽  
Single Dose ◽  
Renal Damage ◽  
Rat Kidney ◽  
Ultrastructural Changes ◽  
Peroxisome Proliferation ◽  
Time Intervals ◽  
Subcellular Organelles ◽  
Renal Tubular Cells ◽  
Renal Tubular

Electron microscopy was used to examine changes in the subcellular organelles of the rat kidney at different time intervals after a single exposure to cyclophosphamide (CP). The morphological changes were studied at different time points (6 hrs, 16 hrs and 24 hrs) after a single-dose administration of CP. Six rats were killed at each time intervals after the administration of CP. Saline-treated rats served as controls. CP administration resulted in alterations in various subcellular organelles including peroxisomes, lysosomes, mitochondria, and the endoplasmic reticulum (ER) of the renal tubular epithelium as well as damage to the glomerulus. The basement membrane of the glomerulus was thickened. Many podocytes were destroyed. The nucleoplasm of the endothelial cell showed fewer granularities. The tubules were distorted and the brush border was destroyed. Two striking features in the renal tubular cells are increase in number and size of the peroxisomes (peroxisome proliferation) and decrease in the number of lysosomes. The mitochondria were elongated and the number was increased in the tubules of CP-treated rats. The ER was dilated. Cell necrosis was also seen. This study is an evidence of changes in morphology of rat kidney after induction of renal damage by a single dose of CP. Since transmission electron microscopy is the highest magnification tool at present, it can be useful in estimating the degree of injury and outcome of alternative treatment strategies in the management of CP-induced renal damage after establishing a scoring system.

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