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drug effects on kidney function

Kanwal Rehman, Kiran Saeed, Syeda Mehak Munawar, Muhammad Sajid Hamid Akash
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is associated with variable degrees of glucose intolerance, impaired insulin secretion, insulin resistance and increased hepatic glucose production. The aim of present study was to investigate the therapeutic potentials of resveratrol (RSV) alone and/or in combination with vitamin-E (Vit-E) against hyperglycemia-induced modulations using experimentally alloxan-induced diabetic animal model. Alloxan was used to induce diabetes mellitus in white albino rats and metformin (MF) was used as standard anti-diabetic drug to compare the therapeutic potentials of RSV (alone and/or with Vit-E) by estimating the effect of treatment on glycemia, insulin resistance, liver and kidney function biomarkers, anti-oxidant status, and serum levels of calcium and magnesium...
March 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhaojian Xiang, Weike Li, Lixue Wang, Jicai Yi, Kaiwen Chen, Mei Hong
Organic anion-transporting polypeptides (OATPs; gene symbol SLCO) are membrane transporters that mediate the transport of wide ranges of compounds. Expression of different OATP members has been reported in the kidney, liver, placenta, brain, and intestine. Due to their broad substrate spectra and wide distribution within human body, these transporters have been proposed to play key roles in the influx transport of many oral drugs. Inflammation is known to regulate the expression and functions of many drug-metabolizing enzymes and drug transporters...
March 16, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Thomas F Gamage, Charlotte E Farquhar, Timothy W Lefever, Julie A Marusich, Richard C Kevin, Iain S McGregor, Jenny L Wiley, Brian F Thomas
Synthetic cannabinoids are a class of novel psychoactive substances that exhibit high affinity at the cannabinoid type-1 (CB1) receptor and produce effects similar to those of THC, the primary psychoactive constituent of cannabis. Illicit drug manufacturers are continually circumventing laws banning the sale of synthetic cannabinoids by synthesizing novel structures and doing so with little regard for their potential impact on pharmacological and toxicological effects. Synthetic cannabinoids produce a wide range of effects including cardiotoxicity, seizure activity, and kidney damage and can result in death...
March 16, 2018: Journal of Pharmacology and Experimental Therapeutics
Yong-Soon Cho, Yook-Hwan Noh, Hyeong-Seok Lim, Sang-Heon Cho, Jong-Lyul Ghim, Sangmin Choe, Soon-Bae Kim, Jung-Sik Park, Sang-Koo Lee, Won-Seok Yang, Jai-Won Chang, Mi-Young Bahng, Kyun-Seop Bae
Udenafil is a phosphodiesterase-5 inhibitor used to treat erectile dysfunction. Although udenafil is not predominantly eliminated by the kidney, renal impairment can alter its secretion/transport pathways. Drug pharmacokinetics and safety must therefore be assessed in subjects with a renal impairment. We investigated the effects of impaired renal function on the pharmacokinetics and safety of a single 100-mg oral dose of udenafil in a single-dose, open-label, parallel-group study of 31 subjects. Cockcroft-Gault creatinine clearance was used to stratify these subjects into healthy controls (>80 mL·min-1 ) and individuals with mild (50 to ≤80 mL·min-1 ), moderate (30 to ≤50 mL·min-1 ), and severe (<30 mL·min-1 ) renal impairment...
March 14, 2018: Journal of Clinical Pharmacology
Zohaib Ahmed Bhutto, Fang He, Mire Zloh, Jing Yang, Jinhu Huang, Tingting Guo, Liping Wang
Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken...
March 13, 2018: Scientific Reports
Miguel Fontecha-Barriuso, Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Maria Dolores Sanchez-Niño, Lara Valiño-Rivas, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease...
March 9, 2018: Nephrology, Dialysis, Transplantation
B Chantemargue, F Di Meo, K Berka, N Picard, H Arnion, M Essig, P Marquet, M Otyepka, P Trouillas
The ABCC4/MRP4 exporter has a clinical impact on membrane transport of a broad range of xenobiotics. It is expressed at key locations for drug disposition or effects such as in the liver, the kidney and blood cells. Several polymorphisms and mutations (e.g., p.Gly187Trp) leading to MRP4 dysfunction are associated with an increased risk of toxicity of some drugs. So far, no human MRP4 structure has been elucidated, precluding rationalization of these dysfunctions at a molecular level. We constructed atomistic model of the wild type (WT) MRP4 and the p...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Moomal Tasneem, Carly Mannix, Annette Wong, Jennifer Zhang, Gopala Rangan
The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]...
March 6, 2018: World Journal of Nephrology
Georgina P Ossani, Diego J Martino, Jorge E Toblli
Lithium has been approved for the treatment of bipolar disorder since the 1970s and even today it is considered a first-line drug for the treatment of this disease. As bipolar disorder often begins between 15-35 years of age and requires long-term treatment, the assessment of the adverse effects of the drugs used is critical. Recently, there has been renewed interest on the risk of chronic kidney disease and kidney failure induced by lithium, with findings suggesting that both complications could be more frequent than previously considered...
September 2017: Vertex: Revista Argentina de Psiquiatriá
Comfort Omoigemete Olurishe, Helen Ochuko Kwanashie, Abdulkadiri Umar Zezi, Nuhu Mohammed Danjuma, Bisalla Mohammed
OBJECTIVE: Sitagliptin (ST) and Moringa oleifera (MO) Lam (Moringaceae) are used concomitantly by diabetic patients, with no study ascertaining for potential favorable or otherwise renal implications. We investigated the effect of coadministration of ST and MO leaf extract on functional and morphological biomarkers of alloxan-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Diabetes was induced with a single dose of 150 mg/kg of alloxan intraperitoneally...
September 2017: Indian Journal of Pharmacology
Osamu Ichii, Taro Horino
Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing...
January 2018: Journal of Toxicologic Pathology
Florian Kronenberg
The picture of HDL cholesterol (HDL-C) as the "good" cholesterol has eroded. This is even more surprising because there exists strong evidence that HDL-C is associated with cardiovascular disease (CVD) in the general population as well as in patients with impairment of kidney function and/or progression of CKD. However, drugs that dramatically increase HDL-C have mostly failed to decrease CVD events. Furthermore, genetic studies took the same line, as genetic variants that have a pronounced influence on HDL-C concentrations did not show an association with cardiovascular risk...
February 22, 2018: Journal of the American Society of Nephrology: JASN
Bo Åkerström, Lena Rosenlöf, Anneli Hägerwall, Sigurbjörg Rutardottir, Jonas Ahlstedt, Maria E Johansson, Lena Erlandsson, Maria Allhorn, Magnus G Gram
AIMS: Human A1M (α1-microglobulin) is an endogenous reductase and radical- and heme-binding protein with physiological antioxidant protective functions. Recombinant human A1M (rA1M) has been shown to have therapeutic properties in animal models of preeclampsia, a pregnancy disease associated with oxidative stress. Recombinant A1M, however, lacks glycosylation, and shows lower solubility and stability than A1M purified from human plasma. The aims of this work was to 1) use site-directed mutagenesis to improve the physicochemical properties of rA1M, 2) demonstrate that the physicochemically improved rA1M displays full in vitro cell protective effects as recombinant wild-type A1M (rA1M-wt), and 3) show its therapeutic potential in vivo against acute kidney injury (AKI), another disease associated with oxidative stress...
February 22, 2018: Antioxidants & Redox Signaling
Hina Rasheed, Ruqayya Afridi, Ashraf Ullah Khan, Muhammad Zia Ullah, Sidra Khalid, Ayesha Atiq, Humaira Kashif, Muhammad Naeem Ahmed, Yeong Shik Kim, Salman Khan
Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, the current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity...
February 22, 2018: Inflammopharmacology
Swapnil Hiremath, Jeanne Françoise Kayibanda, Benjamin J W Chow, Dean Fergusson, Greg A Knoll, Wael Shabana, Brianna Lahey, Olivia McBride, Alexandra Davis, Ayub Akbari
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is defined as worsening of renal function after the administration of iodinated contrast material. In patients with cardiovascular disease, kidney disease, and/or diabetes, renin-angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics, and metformin can increase the risk of CI-AKI when undergoing contrast imaging. Despite CI-AKI being the leading iatrogenic cause of acute kidney injury, there is a lack of sufficient scientific evidence supporting which drugs should be stopped, when they should be stopped, and when they should be resumed...
February 21, 2018: Systematic Reviews
Raphael Fabricio de Souza, Dihogo Gama de Matos, Alexandre Reis Pires Ferreira, Philip Chilibeck, Natalie de Almeida Barros, Alan Santos de Oliveira, Luana Mendonça Cercato, Danielle Soares da Silva, Felipe José Aidar
The aim of this study was to investigate the effect of prophylactic use of nonsteroidal anti-inflammatory drugs (NSAID, i.e. Ibuprofen) on physical performance, vertical jump, muscle biomarkers, liver, kidney, acute pain and hydration status of participants in the 42 km Trail Running Challenge, a long-distance race integrated over mountain routes. The sample consisted of 20 males randomly divided into two groups: a control group (CG) and an experimental group (EG) with 12 completing the race (41.1±8.8 y; 75...
February 14, 2018: Journal of Strength and Conditioning Research
Adewale Adewuyi, Chiagoziem A Otuechere, Olusegun L Adebayo, Chibuzo Anazodo, Fabiano V Pereira
Nanocellulose is currently gaining attention due to its unique properties. This attention includes its application as building blocks for developing novel functional materials, plant drug and also in drug delivery systems. However, its safety remains largely untested or less understood. Thus, sulphonated nanocellulose (KSS) was prepared from cellulose (KSC) isolated from Khaya senegalensis seed (KS). KS, KSC and KSS were characterized using Fourier transformed infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), particle size distribution (PSD), zeta potential and scanning electron microscopy (SEM)...
February 16, 2018: Chemico-biological Interactions
Maxim Durand, Florian Dubois, Cécile Dejou, Eugénie Durand, Richard Danger, Mélanie Chesneau, Carole Brosseau, Pierrick Guerif, Jean-Paul Soulillou, Nicolas Degauque, Jean-François Eliaou, Magali Giral, Nathalie Bonnefoy, Sophie Brouard
Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process...
February 15, 2018: Kidney International
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
Rashid A Barnawi, Rahaf Z Attar, Sultan S Alfaer, Osama Y Safdar
Autosomal dominant polycystic kidney disease (ADPKD) causes pathological cystic changes to the kidney and is characterized by numerous renal and systemic manifestations. ADPKD is the fourth most common renal disease requiring renal replacement therapy. In this report, we present a detailed review of ADPKD, with a particular focus on its major economic, psychological, and social burden in affected patients. Treatment of this disease has been based on prophylactic and supportive measures. However, in recent years, new drugs have emerged as promising agents that may retard the progression of ADPKD, such as tolvaptan...
2018: International Journal of Nephrology and Renovascular Disease
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