Influx Of Drugs Research Articles

Penal-welfare systems in a (post)colonial world: The rise and disregard of alcohol and drug rehabilitation centers in South Africa

Apartheid South Africa developed a notoriously punitive and racist approach to alcohol and drug use. Less reported is that the state gave significant attention to rehabilitation, first for the minority white population and later for black South Africans. This paper asks why in the post-apartheid era—despite a huge influx of cheap heroin, methamphetamines, and other drugs—the government showed a relative disregard for rehabilitation. Addressing this question, the paper points to the configuration of forces driving public rehabilitation in the colonial era included the upliftment of “poor whites,” the need to maintain black workers’ productivity, and the ascendancy of the disease concept of addiction. In the post-1994 period these forces waned as a multiracial middle class came to purchase treatment in private rehabilitation facilities, the disease concept fell into retreat, and mass unemployment helped to position poor black drug users as an “undeserving poor.” The paper contributes to comparative studies on penal-welfare systems and the recent attention to drug histories from the global South.

The Use of Carboxyfluorescein Reveals the Transport Function of MCT6/SLC16A5 Associated with CD147 as a Chloride-Sensitive Organic Anion Transporter in Mammalian Cells

Oral drug absorption involves drug permeation across the apical and basolateral membranes of enterocytes. Although transporters mediating the influx of anionic drugs in the apical membranes have been identified, transporters responsible for efflux in the basolateral membranes remain unclear. Monocarboxylate transporter 6 (MCT6/SLC16A5) has been reported to localize to the apical and basolateral membranes of human enterocytes and to transport organic anions such as bumetanide and nateglinide in the Xenopus oocyte expression system; however, its transport functions have not been elucidated in detail. In this study, we characterized the function of MCT6 expressed in HEK293T cells and explored fluorescent probes to more easily evaluate MCT6 function. The results illustrated that MCT6 interacts with CD147 to localize at the plasma membrane. When the uptake of various fluorescein derivatives was examined in NaCl-free uptake buffer (pH 5.5), the uptake of 5-carboxyfluorescein (5-CF) was significantly greater in MCT6 and CD147-expressing cells. MCT6-mediated 5-CF uptake was saturable with a Km of 1.07 mM and inhibited by several substrates/inhibitors of organic anion transporters and extracellular Cl ion with an IC50 of 53.7 mM. These results suggest that MCT6 is a chloride-sensitive organic anion transporter that can be characterized using 5-CF as a fluorescent probe.

Translocation Processes of Pt(II)-Based Drugs through Human Breast Cancer Cell Membrane: In Silico Experiments.

Breast cancer is one of the most frequent modalities of cancer worldwide, with notable mortality. The medication based on platinum drugs (cisplatin (cddp), carboplatin (cpx), and oxaliplatin (oxa)) is a conventional chemotherapy despite severe side effects and the development of drug resistance. In order to provide a deeper molecular description of the influx and efflux processes of platinum drugs through breast cancer tissues, this study focuses on molecular dynamics (MD) simulations of the passive translocation process through a realistic plasma membrane prototype of human breast cancer cell (c_memb). The results showed that the permeation events were mainly mediated by neutral lipids (DOPC, DOPE, and cholesterol), producing a low and temporary membrane deformation. The drug insertion in the region of polar heads was the most favorable stage of the translocation mechanism, especially for cddp and oxa with potential wells of -8.6 and -9.8 kcal mol-1, respectively. However, the potentials of mean force (PMF) revealed unfavorable kinetics for the permeation of these drugs through lipid tails, with energy barriers of 28.3 (cddp), 32.2 (cpx), and 30.4 kcal mol-1 (oxa). The low permeability coefficients (P) of cpx and oxa, which were 3 and 1 orders of magnitude inferior than for cddp, resulted from the high energy barriers for their traslocation processes through the membrane. The obtained results provide a more accurate picture of the permeation of Pt(II)-based drugs through breast cancer cells, which may be relevant for the design and evaluation of new platinum complexes.

The Important Role of Transporter Structures in Drug Disposition, Efficacy, and Toxicity.

The ATP-binding cassette (ABC) and solute carrier (SLC) transporters are critical determinants of drug disposition, clinical efficacy and toxicity, as they specifically mediate the influx and efflux of various substrates and drugs. ABC transporters can modulate the pharmacokinetics of many drugs via mediating the translocation of drugs across biological membranes. SLC transporters are important drug targets involved in the uptake of a broad range of compounds across the membrane. However, high-resolution experimental structures have been reported for a very limited number of transporters, which limits the study of their physiological functions. In this review, we collected structural information on ABC and SLC transporters and described the application of computational methods in structure prediction. Taking P-glycoprotein (ABCB1) and serotonin transporter (SLC6A4) as examples, we assessed the pivotal role of structure in transport mechanisms, details of ligand-receptor interactions, drug selectivity, the molecular mechanisms of drug-drug interactions (DDIs), and variability caused by genetic polymorphisms. The data collected contributes towards safer and more effective pharmacological treatments. Significance Statement The experimental structure of ABC and SLC transporters was collected, and the application of computational methods in structure prediction was described. P-glycoprotein and serotonin transporter were used as examples to reveal the pivotal role of structure in transport mechanisms, drug selectivity, the molecular mechanisms of DDIs, and differences caused by genetic polymorphisms.

Migrace za životním stylem surfaře v marocké vesnici Taghazout a změny, které způsobuje v místním prostředí

In this article, I describe my research in the Moroccan village of Taghazout, where I traced the causes and consequences of significant changes stemming from tourism and lifestyle migration over a period of more than a decade. Originally a fishing village with almost no tourism, it became a sought-after center for surfers from all over the world and a location for foreign investors, which completely changed the character of the site. A large number of these surfers are so-called lifestyle migrants who have permanently settled in Taghazout and formed an international community here – they are mainly British, Dutch, German, French, and Spanish. First, I reflect on my own multi-layered position in the field, and then I focus on surfing as the cause of these changes and the main motive of lifestyle migration. I describe it in terms of the subculture and a lifestyle sport. After that, I focus on lifestyle migration and sports tourism, which are very closely related topics. In the actual analysis of data from the field, I deal with the development of Taghazout itself, and I deal with the types of lifestyle migrants settled in the village, who are most often surfers. I focus more closely on their psychology, motivations, and the types of surfers in the context of the surfing mentality. Finally, I describe the very effects of tourism and migration on the local environment, which include the influx of alcohol and drugs into the village, the effect on bodily exposure, and caring for the environment.

Comparative quality assessment of six commercial brands of metronidazole infusions sold in Abuja, Nigeria

Influx of substandard drugs as reported by the drug regulatory agency in Nigeria has necessitated the need to assess the quality of frequently used drugs of which metronidazole infusion is not exempted. Metronidazole infusion is mostly prescribed for pre and post-operative surgery to prevent infections from developing. This study was carried out to assess the quality of six commercial brands of metronidazole infusions sold in Abuja, Nigeria. Six brands of metronidazole infusions were randomly purchased from some Pharmacy stores in Abuja for chemical and microbiological assays. Five (83.3%) of the samples had percentage contents ranging from 95-110% which is within BP specification. The pH values of the whole samples were within BP specification of 4.5 to 6.0 which range from 4.9 to 5.8. The result of the microbiological analysis indicated zero colony forming unit (cfu) from all the samples, this is in conformity with official specification for parenteral formulations. Similarly, all the brands passed pyrogen test. Based on the percentage content result, five brands of the samples analyzed have been found to be fit for human use while one failed.

The Effect of Single Nucleotide Variations in the Transmembrane Domain of OATP1B1 on in vitro Functionality

PurposeOrganic Anion Transporting Polypeptide 1B1 (OATP1B1) mediates hepatic influx and clearance of many drugs, including statins. The SLCO1B1 gene is highly polymorphic and its function-impairing variants can predispose patients to adverse effects. The effects of rare genetic variants of SLCO1B1 are mainly unexplored. We examined the impact of eight naturally occurring rare variants and the well-known SLCO1B1 c.521C > T (V174A) variant on in vitro transport activity, cellular localization and abundance.MethodsTransport of rosuvastatin and 2,7-dichlorofluorescein (DCF) in OATP1B1 expressing HEK293 cells was measured to assess changes in activity of the variants. Immunofluorescence and confocal microscopy determined the cellular localization of OATP1B1 and LC–MS/MS based quantitative targeted absolute proteomics analysis quantified the amount of OATP1B1 in crude membrane fractions.ResultsAll studied variants, with the exception of P336R, reduced protein abundance to varying degree. V174A reduced protein abundance the most, over 90% compared to wild type. Transport function was lost in G76E, V174A, L193R and R580Q variants. R181C decreased activity significantly, while T345M and L543W retained most of wild type OATP1B1 activity. P336R showed increased activity and H575L decreased the transport of DCF significantly, but not of rosuvastatin. Decreased activity was interrelated with lower absolute protein abundance in the studied variants.ConclusionsTransmembrane helices 2, 4 and 11 appear to be crucial for proper membrane localization and function of OATP1B1. Four of the studied variants were identified as loss-of-function variants and as such could make the individual harboring these variants susceptible to altered pharmacokinetics and adverse effects of substrate drugs.

Intravenously Infused Stem Cells for Cancer Treatment.

Despite the recent influx of immunotherapies and small molecule drugs to treat tumors, cancer remains a leading cause of death in the United States, in large part due to the difficulties of treating metastatic cancer. Stem cells, which are inherently tumoritropic, provide a useful drug delivery vehicle to target both primary and metastatic tumors. Intravenous infusions of stem cells carrying or secreting therapeutic payloads show significant promise in the treatment of cancer. Stem cells may be engineered to secrete cytotoxic products, loaded with oncolytic viruses or nanoparticles containing small molecule drugs, or conjugated with immunotherapies. Herein we describe these preclinical and clinical studies, discuss the distribution and migration of stem cells following intravenous infusion, and examine both the limitations of and the methods to improve the migration and therapeutic efficacy of tumoritropic, therapeutic stem cells.

Pharmacogenetics of tenofovir and emtricitabine penetration into cerebrospinal fluid.

BackgroundBlood-cerebrospinal fluid (CSF) barrier transporters affect the influx and efflux of drugs. The antiretrovirals tenofovir and emtricitabine may be substrates of blood-brain barrier (BBB) and blood-CSF barrier transporters, but data are limited regarding the pharmacogenetics and pharmacokinetics of their central nervous system (CNS) penetration.ObjectivesWe investigated genetic polymorphisms associated with CSF disposition of tenofovir and emtricitabine.MethodWe collected paired plasma and CSF samples from 47 HIV-positive black South African adults who were virologically suppressed on efavirenz, tenofovir and emtricitabine. We considered 1846 single-nucleotide polymorphisms from seven relevant transporter genes (ABCC5, ABCG2, ABCB1, SLCO2B1, SCLO1A2, SLCO1B1 and ABCC4) and 782 met a linkage disequilibrium (LD)-pruning threshold.ResultsThe geometric mean (95% confidence interval [CI]) values for tenofovir and emtricitabine CSF-to-plasma concentration ratios were 0.023 (0.021–0.026) and 0.528 (0.460–0.605), respectively. In linear regression models, the lowest p-value for association with the tenofovir CSF-to-plasma ratio was ABCB1 rs1989830 (p = 1.2 × 10−3) and for emtricitabine, it was ABCC5 rs11921035 (p = 1.4 × 10−3). None withstood correction for multiple testing.ConclusionNo genetic polymorphisms were associated with plasma, CSF concentrations or CSF-to-plasma ratios for either tenofovir or emtricitabine.

Revolutionary Approach towards Transdermal Drug Delivery: Ethosomal Gels

The human body is up of the skin which is the largest organ in the body and hence acts as a biological barrier that obstructs drug movement across the stratum corneum into the systemic circulation. The topical drug delivery system serves as a delivery system in which drugs are delivered for systemic circulation through the skin. Low diffusion rate across the stratum corneum is the main disadvantage of this system and for this limitation to be overcome, an Ethosomal formulation can be formulated which acts as a delivery system for the drug to be delivered across the biological barrier of the skin into the body. In ethosomal gel formulation, The prepared Ethosome is converted into a gel that can be applied to the skin what makes ethosomal gel formulation unique which enables drugs to reach the deep skin layers and/or the systemic circulation and enhance the delivery of active agents. In addition to this, it is also a malleable vesicular delivery carrier, soft and non-invasive. There is also a higher influx of drugs transdermally into the skin as ethosomal gel formulation allows drug to penetrate deep into the skin and enters systemic circulation. There is the development of new and novel therapies for the treatment of disease through the ethosomal drug delivery system as it is safe and effective and also easy to prepare. Topics ranging from preparation of ethosomes, Ethosomal gel, advantages and disadvantages, and characterization techniques are focused on in this review article.

RPS urges action to prevent influx of post-Brexit counterfeit drugs

RPS urges action to prevent influx of post-Brexit counterfeit drugs

Resistance of Neisseria gonorrhoeae isolates to beta-lactam antibiotics (benzylpenicillin and ceftriaxone) in Russia, 2015-2017.

The goal of this work was to study the phenotypic susceptibility and resistance determinants of N. gonorrhoeae isolates to beta-lactam antimicrobials (benzylpenicillin and ceftriaxone). A total of 522 clinical isolates collected in Russia in 2015–2017 were analysed for susceptibility using the agar dilution method. DNA loci involved in antimicrobial resistance were identified using DNA microarray analysis and sequencing. Resistance to benzylpenicillin remained high, with 7.7% of isolates resistant (MICpen > 1 mg/L) and 47.5% of isolates showing intermediate susceptibility (MICpen = 0.12–1 mg/L). The most frequent resistance determinant (72.4% isolates) was the Asp345 insertion in penA, both as a single mutation and in combination with other mutations, particularly with the substitution Leu421Pro in ponA (39.0%). Mutations affecting the influx and efflux of drugs were also found, including amino acid substitutions in PorB (26.8% isolates) and delA in the promoter region of mtrR (22.8%). The accumulation of mutations in chromosomal genes (penA, pon, porA, and mtrR) led to a stepwise increase in MICpen to values characteristic of intermediate resistance. The presence of blaTEM plasmids was found in 25 isolates (4.8%), resulting in a strong increase in resistance to penicillin (MICpen > 16 mg/L) compared with the chromosomal mutations; 23 plasmids were of the African type with TEM-1 beta-lactamase, and two plasmids were of the Toronto/Rio type with TEM-135 beta-lactamase. Only three isolates were found with reduced susceptibility to ceftriaxone, with MICcef = 0.12–0.25 mg/L. Sequencing of penA did not reveal mutations associated with resistance to third-generation cephalosporins, and the gene structure was non-mosaic. The majority of isolates (21 of 25) carrying the blaTEM plasmid also contained the conjugative plasmid with tetM (resistance to tetracyclines), consistent with previously reported data that the presence of the conjugative plasmid facilitates the transfer of other plasmids associated with antimicrobial resistance.

Electrochemotherapy in the treatment of neoplasms in dogs and cats

Abstract: Electrochemotherapy (ECT) is a technique that combines chemotherapy with local application of specific electric pulses with the aim of increasing the permeability of the plasma membrane in a reversible way, improving the influx of chemotherapeutic drugs into the cytoplasm and potentiating their cytotoxic effects. This technique has broadened the range of possible treatments for oncological patients, either on its own or as adjuvant to surgical procedures. It is especially useful in tumors located in regions with only a small surgical safety margin, such as the limb extremities, skull, oral cavity, neck and perianal region, among others. ECT makes it feasible to perform procedures more conservatively, or even to perform otherwise infeasible procedures, by expanding the margins without removing healthy tissues. The objective of this paper is to provide a brief bibliographic review of the principles, applications and future possibilities of electrochemotherapy, helping to disseminate pertinent information about this relatively new technique for the treatment of cancer.

Challenges in forensic toxicology

ABSTRACTThe scope of forensic toxicology has expanded tremendously over the past 40 years. As the field of forensic toxicology expands and improves, forensic toxicologists continue to face multiple challenges, such as the emergence of new drugs, different standards among laboratories, and discrepancies in the interpretation of toxicological findings. New psychoactive substances (NPS) have been the centre of attention since 2009 in all areas of forensic toxicology, including drug testing. Owing to the constant influx of new drugs and the lack of reference standards, the detection and quantification of NPSs in biological fluids are significant challenges for forensic toxicologists. Furthermore, forensic toxicologists aspire to attain the highest analytical standard in each laboratory. However, there are limited resources for adequate staffing, technology, and training. Experience and expertise, and the availability of high-end instruments, have vital impacts on the quality of a laboratory. The interpretation of post-mortem toxicological data is another major challenge. Determination of the level of a drug in post-mortem specimens, post-mortem redistribution and the influence of putrefaction on drug disposition are jobs for forensic toxicologists. In conclusion, forensic toxicologists should collaborate, coordinate, communicate with colleagues, investigators, pathologists, judges, persecutors, and defence lawyers to ensure justice for all.

Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues.

Membrane transport protein organic anion transporting polypeptide (OATP) 1B3 mediates the cellular uptake of many clinically important drugs including anti-cancer drugs (e.g., paclitaxel). In addition to the well-recognized hepatic expression and function of OATP1B3 [herein named liver-type (Lt) OATP1B3], OATP1B3 also expresses in cancers and has been postulated to play a role in cancer therapy, presumably by facilitating the influx of anti-cancer drugs. Recently, a cancer type (Ct)-OATP1B3 mRNA variant was identified in colon and lung cancer tissues, which encodes truncated Ct-OATP1B3 with negligible transport activity. Other than in colon and lung cancers, reports on mRNA expression of OATP1B3 in other cancers cannot distinguish between the Ltand Ct-OATP1B3. The current studies were designed to characterize the expression of Lt- and Ct-OATP1B3 mRNA in ovarian, prostate, bladder, breast, and lung tissues. Lt- and Ct-OATP1B3 isoform-specific PCR primers were utilized to determine the mRNA levels of Lt- and Ct-OATP1B3, respectively. An expression vector expressing green fluorescent protein (GFP)-tagged Lt-OATP1B3 was transiently transfected into the ovarian cancer cell line SKOV3. Confocal live-cell microscopy was utilized to determine the localization of GFP-Lt-OATP1B3 in SKOV3 cells. For the first time, Lt-OATP1B3 mRNA was detected in ovarian, prostate, bladder and breast cancers. The localization of GFP-Lt-OATP1B3 on the plasma membrane of SKOV3 cells after transient transfection was readily detected by confocal microscopy. Our findings are supportive of the potential role of Lt-OATP1B3 in cancer cells.

The inhibitory effects of eighteen front-line antibiotics on the substrate uptake mediated by human Organic anion/cation transporters, Organic anion transporting polypeptides and Oligopeptide transporters in in vitro models

Human Organic anion/cation transporters (OATs/OCTs), Organic anion transporting polypeptides (OATPs) and proton-coupled Oligopeptide transporters (PepTs) are important membrane transporters responsible of the cellular influx of drugs in many human key tissues. Inhibitor(s) impacting on the cellular uptake of transporter drug substrates is one of the primary causes of drug-drug interactions that lead to unsatisfied therapeutic outcomes and/or unwanted side effects. In the current study, we selected eighteen antibiotic agents used in infectious disease treatment and comprehensively evaluated their inhibitory effects on the substrate uptake mediated through the essential OATs/OCTs, OATPs and PepTs isoforms. Transport functional assay, dose-response curve and kinetic analysis were performed on the HEK293 cells over-expressing each of these transporter genes. Our data revealed that nitrofurantoin, sulfadiazine and metronidazole significantly inhibited the transport activity of OAT3 (IC50 values of 6.23±1.33μM, 6.65±1.30μM and 6.51±0.99μM; Ki values of 5.86μM, 3.98μM and 6.48μM, respectively). Trimethoprim and ciprofloxacin potently decreased the substrate uptake mediated via OATP1A2 (IC50 values of 9.35±1.10μM and 9.25±1.18μM; Ki values of 8.19μM and 7.64μM, respectively). In addition, these antibiotic agents consistently decreased methotrexate influx via OAT3 and OATP1A2. In summary, our study is the first to show that nitrofurantoin, sulfadiazine and metronidazole are potent inhibitors of OAT3 and trimethoprim is a novel inhibitor of OATP1A2. Our study also provides new evidence for the drug-drug interactions of ciprofloxacin with OATP1A2 drug substrates like methotrexate. Therefore, precautions are required when co-administering these antibiotics with OAT3 or OATP1A2 drug substrates.

Quality Assessment of Selected Vitamin C Tablets Sold at Bridge Head Market, Onitsha

Due to the importance of ascorbic acid in humans, qualitative and quantitative evaluation of ascorbic acid has gained a significant increase in several areas of analytical chemistry such as pharmaceutical analysis. Several analytical methods have been developed. Most of these methods are laborious and some require much reagents that may be either not readily available or are expensive. There is an influx of counterfeit drugs in the market and due to this, two questions come up; are we underdozed? Or overdozed? This is a research on the quality of selected brands of Vitamin C tablets. In this research work, five brands of Vitamin C tablets were purchased at Bridge head market, Onitsha and were analyzed for their percentage content of Ascorbic Acid (active pharmaceutical product), their average percentage friability, disintegration time and hardness using a UV/Vis spectrophotometer, friabilator, disintegration tester and hardness tester. The results showed that they all passed the hardness and disintegration time test. Samples 1, 3, 4, and 5 failed the test for the percentage content of Ascorbic acid; Sample 2 failed the friability test. Sample 2 has proven to have the highest quality and would be able to enact action faster since it has the highest quantity of Ascorbic acid that will be disintegrated at any time and this also means that it will be absorbed into the blood stream faster.

Illicit Drug Trafficking in Nigeria: Obstacle to National Development and Security

One of the actual threats to the nation’s and human security is the alarming rate of illicit drug trafficking (IDT). The menace of illicit drug trafficking poses heinous threats to human lives, national development and security. Most of the Nigerian borders are porous, therefore, giving room for easy influx, movement and exit of drugs. However, the failing economy, insecurity, high rate of graduate unemployment, poverty, failure of government to provide basic necessities of life, high level of corruption and get-rich-quickly syndrome among the youths in Nigeria, constitute the various banes behind the practice of illicit drug trafficking in the state. This study interrogates the obstacles and threats posed by drug trafficking to human lives, state’s development and national security; it assesses the concerted efforts of the Nigerian government aimed at combating the menace with a plan to proffer solutions on how to checkmate the disheartening phenomenon. The study concludes that, lack of adequate intelligence gathering, insecurity, bribery and corruption, poverty, civilization and porous borders stand as a cog in the wheel to appreciable efforts at arresting the menace in the country. It also submits that there is need for sound orientation/education, strong law and good governance, adequate intelligence gathering to solve the problem in addition to the imperative role of law enforcement agencies for sustenance of a drug-free society and state.

Selective Inhibition of Human Equilibrative and Concentrative Nucleoside Transporters by BCR-ABL Kinase Inhibitors: IDENTIFICATION OF KEY hENT1 AMINO ACID RESIDUES FOR INTERACTION WITH BCR-ABL KINASE INHIBITORS

Human nucleoside transporters (hNTs) mediate cellular influx of anticancer nucleoside drugs, including cytarabine, cladribine, and fludarabine. BCR-ABL tyrosine kinase inhibitors (TKIs) imatinib and dasatinib inhibit fludarabine and cytarabine uptake. We assessed interactions of bosutinib, dasatinib, imatinib, nilotinib, and ponatinib with recombinant hNTs (hENT1, 2; hCNT1, -2, and -3) produced individually in yeast Saccharomyces cerevisiae Nilotinib inhibited hENT1-mediated uridine transport most potently (IC50 value, 0.7 μm) followed by ponatinib > bosutinib > dasatinib > imatinib. Imatinib inhibited hCNT2 with an IC50 value of 2.3 μm Ponatinib inhibited all five hNTs with the greatest effect seen for hENT1 (IC50 value, 9 μm). TKIs inhibited [(3)H]uridine uptake in a competitive manner. Studies in yeast with mutants at two amino acid residues of hENT1 (L442I, L442T, M33A, M33A/L442I) previously shown to be involved in uridine and dipyridamole binding, suggested that BCR-ABL TKIs interacted with Met(33) (TM1) and Leu(442) (TM11) residues of hENT1. In cultured human CEM lymphoblastoid cells, which possess a single hNT type (hENT1), accumulation of [(3)H]cytarabine, [(3)H]cladribine, or [(3)H]fludarabine was reduced by each of the five TKIs, and also caused a reduction in cell surface expression of hENT1 protein. In conclusion, BCR-ABL TKIs variously inhibit five different hNTs, cause a decrease in cell surface hENT1 expression, and decrease uridine accumulation when presented together with uridine or when given before uridine. In experiments with mutant hENT1, we showed for the first time interaction of Met(33) (involved in dipyridamole binding) with BCR-ABL inhibitors and reduced interaction with M33A mutant hENT1.

Assessment of mutagenic, hematological and oxidative stress biomarkers in liver of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) in response to sublethal verapamil exposure

The influx of pharmaceutical drugs and their metabolites have been reported to cause negative impact on aquatic biota. In this study, effects of long-term exposure of verapamil on mutagenic, hematological parameters and activities of the oxidative enzymes of Nile tilapia, Oreochromis niloticus were investigated for 60 days exposure at the concentrations of 0.29, 0.58 and 1.15 mg L−1 in the fish liver. The exposure resulted in significantly high (p < 0.05) micronuclei induction of peripheral blood cells at the peak on day 30 at 1.15 mg L−1. Compared with the control, there was significant increase (p < 0.05) in white blood cell counts and red blood cell distribution width (RDW), with a reduction in hemoglobin (Hb), red blood cell counts (RBCs), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) level as the concentration of the drug increased. The indices of oxidative stress biomarkers (lipid peroxidation and carbonyl protein) showed elevated level, depicting a positive correlation with both time and concentration. More so, the activity of energy-related parameter (Na+ -K+- ATPase) in the tissue was significantly inhibited (p < 0.05) at the end of 60 days exposure period. Further, the activity of catalase (CAT) was inhibited while reduced glutathione (GSH) level was decreased in the liver tissue. There was increase in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione–S-transferase (GST) after 30 days at 0.29 mg L−1. The study demonstrated that prolonged exposure to verapamil at sublethal concentration can result in mutagenic effects and oxidative dysfunctions in O. niloticus.