In vitro genotoxic perspective of Tamiflu

İla, Hasan Basri; İlhan, Ahmet

doi:10.1007/s10616-011-9422-1

Cited by 9 publications

(5 citation statements)

References 14 publications

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“…The progesterone variant Megestrol acetate exhibited antagonisitic activity toward the AR with a submicromolar IC 50 value. From a biological standpoint, these observations make sense for the possible overall phenotypic consequences, as exemplified by the phenotypic feminization observed in animal models upon administration of Vinclozolin (Ila and Ilhan, 2012;Jamieson et al, 2009). From a compound screening perspective, these results suggested that the screening of multiple NHRs is likely to be necessary to gain a comprehensive understanding to the overall in vivo consequences.…”

Section: Steroid Compoundsmentioning

confidence: 95%

“…Marketed under the trade name, Tamiflu, Oseltamivir is an antiviral drug used to treat influenza infection (Genentech USA, 2011). A study carried out by Ila and Ilhan (2012) using human lymphocytes showed that Oseltamivir decreased the proliferation index and nuclear division index, indicating it had a mild cytotoxic effect. However, the cytotoxic effects were no longer observed when adding an exogenous metabolic activation system (S9 mix) into the cell culture, suggesting that this particular cytotoxicity could be mitigated by metabolism (Ila and Ilhan, 2012).…”

Section: Nonsteroid Compoundsmentioning

confidence: 99%

“…A study carried out by Ila and Ilhan (2012) using human lymphocytes showed that Oseltamivir decreased the proliferation index and nuclear division index, indicating it had a mild cytotoxic effect. However, the cytotoxic effects were no longer observed when adding an exogenous metabolic activation system (S9 mix) into the cell culture, suggesting that this particular cytotoxicity could be mitigated by metabolism (Ila and Ilhan, 2012). The mild cytotoxicity does not fully explain the positive agonistic results of Oseltamivir, observed in cellular assay.…”

Section: Nonsteroid Compoundsmentioning

confidence: 99%

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Utilization of Human Nuclear Receptors as an Early Counter Screen for Off-Target Activity: A Case Study with a Compendium of 615 Known Drugs

Fan¹,

Hu²,

Munzli³

et al. 2015

Toxicol. Sci.

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Off-target effects of drugs on nuclear hormone receptors (NHRs) may result in adverse effects in multiple organs/physiological processes. Reliable assessments of the NHR activities for drug candidates are therefore crucial for drug development. However, the highly permissive structures of NHRs for vastly different ligands make it challenging to predict interactions by examining the chemical structures of the ligands. Here, we report a detailed investigation on the agonistic and antagonistic activities of 615 known drugs or drug candidates against a panel of 6 NHRs: androgen, progesterone, estrogen α/β, and thyroid hormone α/β receptors. Our study revealed that 4.7 and 12.4% compounds have agonistic and antagonistic activities, respectively, against this panel of NHRs. Nonetheless, potent, unintended NHR hits are relatively rare among the known drugs, indicating that such interactions are perhaps not tolerated during drug development. However, we uncovered examples of compounds that unintentionally agonize or antagonize NHRs. In addition, a number of compounds showed multi-NHR activities, suggesting that the cross-talk between multiple NHRs co-operate to elicit in vivo effects. These data highlight the merits of counter screening drug candidate against NHRs during drug discovery/development.

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Section: Steroid Compoundsmentioning

confidence: 95%

Section: Nonsteroid Compoundsmentioning

confidence: 99%

Section: Nonsteroid Compoundsmentioning

confidence: 99%

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Utilization of Human Nuclear Receptors as an Early Counter Screen for Off-Target Activity: A Case Study with a Compendium of 615 Known Drugs

Fan¹,

Hu²,

Munzli³

et al. 2015

Toxicol. Sci.

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“…Febrile seizures are a clinical diagnosis with still unknown exact etiology; however, even so, Choi et al [13] noted that high levels of proinflammatory cytokines released during viral infection may be linked to the onset of febrile seizures in pediatric patients, likely because of the still developing brain. Additionally, it is worth noting that oseltamivir has been shown to be weakly cytotoxic [14]; regardless of when our patient took oseltamivir, it was unlikely to have had any contribution to the onset of seizure-like activity.…”

Section: Our Suspicion For Rhinovirusmentioning

confidence: 79%

Severe Pulmonary Infection in a 20-Month-Old Female

Mann

Zeller

Carrillo-Kappus

et al. 2020

Case Reports in Infectious Diseases

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Community-Acquired Pneumonia (CAP) is a common reason for hospitalization of a pediatric patient. We report a 20-monthold female admitted for suspected CAP. History included a week-long cough, fever, dyspnea, single occurrence of seizure-like activity, and a sick contact. Initial chest X-ray (CXR) showed left lower lobe pneumonia and parapneumonic effusion with a complex left pleural effusion. Ultrasound findings prompted the need for contrast-enhanced computed tomography (CT) of the chest. Contrast-enhanced CT of the chest confirmed a large pleural effusion with major atelectasis and mediastinal shift. e patient was treated with empiric antibiotics, video-assisted thoracoscopic surgical (VATS) decortication of empyema, and chest tube placement. Due to intraoperative complications, the VATS decortication was aborted and patient was transferred to the pediatric intensive care unit (PICU). A thoracentesis with culture failed to isolate a bacterial organism. Dexamethasone was started after repeat CXR showed persistent infiltrate. Subsequent contrast-enhanced CT of the chest showed a large collection of air and persistent consolidation. e patient received repeat VATS decortication and reinsertion of a chest tube. Repeat pleural fluid cultures failed to isolate a bacterial organism. Infectious disease (ID) consult recommended linezolid 140 mg Q8H for 4 weeks. Seven days after second VATS, a respiratory pathogen panel was positive for rhinovirus/enterovirus. With resolution of leukocytosis and clinical improvement, the patient was discharged with the chest tube in place and pediatric surgery outpatient follow-up. After three months, sequalae from both the infection and interventions presented .A 20-month-old Caucasian female presented to the Emergency Department (ED) with complaint of a week-long cough, fever, difficulty breathing, and a single instance of apparent seizure-like activity that resolved. She was seen at an urgent care 7 days prior to ED presentation and given prescriptions for albuterol and oseltamivir for suspicion of

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“…Our results support that situation. Same is true for oseltamivir which is not mutagenic at therapeutic and higher concentrations (Ila & Ilhan, 2012). Ribavirin has been tested widely for its mutagenicity through different models.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cytotoxic, antiviral effect and mutagenic potential of a micronutrient combination in vitro cell culture

Matti

Ashraf

Rasheed

et al. 2020

Preprint

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Background: Micronutrients are essential for the body to produce enzymes, hormones and other substances essential for proper growth and development. Iodine, potassium iodide and ascorbic acid are ones of the most important in global public health terms. However, their lack represents a major threat to the human and animal health.Methodology: Antiviral, cytotoxic and mutagenic activity of commercially available micronutrient combination consisting of iodine, ascorbic acid, potassium iodide and excipients was evaluated. Commercial preparation of micronutrient combination was compared with self-prepared micronutrient preparation. MTT assay was used to evaluate the cytotoxicity of all the preparation.Confluent monolayer of Chicken Embryo Fibroblasts grown in 96-well cell culture plates were treated with ten concentrations of each preparation in triplicate manner and was used to determine the viability of the cells and cell survival percentage. Antiviral efficacy was determined against influenza virus H9N1 strain by virus infection and subsequent cell viability assay. Furthermore, mutagenicity was measured by bacterial reverse mutation analysis by Ames test using two strains of Salmonella typhimurium TA100 and TA 98 with and without S9. After appropriate incubation, number of revertant colonies per plate were counted in triplicate manner and MF was calculated.Results: Our combination showed cytotoxicity at doses higher than 11.71ug/ml while showed significant antiviral efficacy at concentrations of 11.71ug/ml, 5.86ug/ml, 2.93ug/ml and 1.4ug/ml which faded away at lower dilutions. Commercially available preparation was found to be nonmutagenic in our experiment. Conclusions:Combination consisting of iodine, ascorbic acid, potassium iodide is effective in the treatment of viral infections.

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In vitro genotoxic perspective of Tamiflu

Cited by 9 publications

References 14 publications

Utilization of Human Nuclear Receptors as an Early Counter Screen for Off-Target Activity: A Case Study with a Compendium of 615 Known Drugs

Utilization of Human Nuclear Receptors as an Early Counter Screen for Off-Target Activity: A Case Study with a Compendium of 615 Known Drugs

Severe Pulmonary Infection in a 20-Month-Old Female

Evaluation of cytotoxic, antiviral effect and mutagenic potential of a micronutrient combination in vitro cell culture

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