scholarly journals Possible role of glutathione peroxidase-3 and organic cation transporter-2 gene expressions in mediating protective effects of curcumin on cisplatin‐induced nephrotoxicity in rats

2020 ◽  
Vol 24 (3) ◽  
pp. 211-220
Author(s):  
Abdolrahman Biabangard ◽  
◽  
Naser Khalaji ◽  
Morteza Bagheri ◽  
Bagher Pourheydar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Peroxidation ◽  
Glutathione Peroxidase ◽  
Serum Creatinine ◽  
Organic Cation ◽  
Kidney Tissue ◽  
Organic Cation Transporter ◽  
Tunel Staining ◽  
Cisplatin Nephrotoxicity

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.

Possible Protective Effects of Curcumin via Modulating of Androgen Receptor (AR) and Oct2 Gene Alterations in Cisplatin‐Induced Testicular Toxicity in Rat

2020 ◽  
Vol 20 ◽  
Author(s):  
Amin Abdollahzade Fard ◽  
Mahrokh Samadi ◽  
Abdolrahman Biabangard
Keyword(s):  
Gene Expression ◽  
Androgen Receptor ◽  
Organic Cation ◽  
Tissue Injury ◽  
Kidney Tissue ◽  
Organic Cation Transporter ◽  
Testicular Toxicity ◽  
Protective Effects ◽  
Gene Expressions ◽  
Left Testis

Background: Cisplatin is a chemotherapy drug used to treat testicular cancer that induces testicular toxicity. This study aimed to investigate the possible role of androgens, androgen receptor, and organic cation transporter 2 (OCT2) in the protective effects of curcumin on cisplatin-induced testicular toxicity. Methods: Thirty male Wistar rats were divided into five groups: 1- control (normal saline, 0.5 ml ip, daily for 10 consecutive days); 2- cisplatin (10 mg/kg ip, single dose at the first day); 3- cisplatin + curcumin (10 mg/kg ip, dissolved in 5% DMSO, daily for 10 consecutive days); 4- cisplatin + vehicle (DMSO 5%, 0.3 ml ip); and 5- curcumin (10 mg/kg ip). At the end of the study, a blood sample was obtained for testosterone measurement. The left testis was kept at -80℃ to measure androgen receptor (AR) and type 2 organic cation transporter (OCT2) gene expression and the right testis were kept in 10% formalin for histological analysis. Results: Cisplatin significantly decreased serum testosterone, declined testis AR gene expression, and increased OCT2 gene expression in testis (p<0.01). Curcumin treatment significantly prevented these alterations in testosterone and gene expressions (p<0.01). Moreover, curcumin significantly reversed the cisplatin-induced kidney tissue injury and increased spermatid and spermatozoa. Conclusion: It is concluded that the ameliorative effect of curcumin in cisplatin-induced reproductive disorders was due to the modulation of testosterone and androgen receptors.

scholarly journals Antidepressant potential of organic cation transporter blockade: the role of norepinephrine (1144.5)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Nathan Mitchell ◽  
Rebecca Horton ◽  
Melissa Vitela ◽  
Georgianna Gould ◽  
Wounter Koek ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter

Temporal induction of clusterin in cisplatin nephrotoxicity.

1997 ◽  
Vol 8 (2) ◽  
pp. 302-305
Author(s):  
J R Silkensen ◽  
A Agarwal ◽  
K A Nath ◽  
J C Manivel ◽  
M E Rosenberg
Keyword(s):  
Serum Creatinine ◽  
Time Course ◽  
Tissue Injury ◽  
Kidney Tissue ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
Creatinine Concentration ◽  
Cisplatin Nephrotoxicity ◽  
Tubular Necrosis ◽  
Outer Stripe

Clusterin is a ubiquitous glycoprotein induced in many organs, including the kidney, at times of tissue injury and/or remodeling. It is speculated in this study that clusterin preserves cell interactions that are otherwise perturbed by renal insults. The purpose of this study was to examine clusterin expression after cisplatin nephrotoxicity, a model characterized by a delayed time course of injury and a well-defined site of that injury (proximal tubule). Sprague-Dawley rats were treated with intravenous cisplatin (6 mg/kg) or vehicle. Serum creatinine concentrations were measured and kidneys harvested at 1, 2, and 5 days. Marked induction of clusterin mRNA was seen only at 5 days, a time when serum creatinine concentration was the highest. Histology of kidney tissue 5 days after cisplatin administration revealed marked tubular necrosis localized to the outer stripe of the outer medulla, a region rich in proximal tubules. Immunohistochemistry and in situ hybridization at 5 days demonstrated clusterin primarily in the inner stripe of the outer medulla. In conclusion, expression of clusterin follows renal injury with cisplatin at a time corresponding to the morphologic evidence of tubular necrosis and cell detachment; quite surprisingly, such expression occurs at a site distant from the primary injury.

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 Role of Organic Cation Transporter 3 and Plasma Membrane Monoamine Transporter in the Rewarding Properties and Locomotor Sensitizing Effects of Amphetamine in Male andFemale Mice

2021 ◽  
Vol 22 (24) ◽  
pp. 13420
Author(s):  
Nikki J. Clauss ◽  
Wouter Koek ◽  
Lynette C. Daws
Keyword(s):  
Plasma Membrane ◽  
Knockout Mice ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Monoamine Transporter ◽  
Stimulant Effect ◽  
Stimulant Drugs ◽  
Males And Females ◽  
Organic Cation Transporter 3

A lack of effective treatment and sex-based disparities in psychostimulant addiction and overdose warrant further investigation into mechanisms underlying the abuse-related effects of amphetamine-like stimulants. Uptake-2 transporters such as organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT), lesser studied potential targets for the actions of stimulant drugs, are known to play a role in monoaminergic neurotransmission. Our goal was to examine the roles of OCT3 and PMAT in mediating amphetamine (1 mg/kg)-induced conditioned place preference (CPP) and sensitization to its locomotor stimulant effects, in males and females, using pharmacological, decynium-22 (D22; 0.1 mg/kg, a blocker of OCT3 and PMAT) and genetic (constitutive OCT3 and PMAT knockout (−/−) mice) approaches. Our results show that OCT3 is necessary for the development of CPP to amphetamine in males, whereas in females, PMAT is necessary for the ability of D22 to prevent the development of CPP to amphetamine. Both OCT3 and PMAT appear to be important for development of sensitization to the locomotor stimulant effect of amphetamine in females, and PMAT in males. Taken together, these findings support an important, sex-dependent role of OCT3 and PMAT in the rewarding and locomotor stimulant effects of amphetamine.

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.

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