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Drug and Chemical Toxicology

Simon Loiodice, Andre Nogueira da Costa, Franck Atienzar
The development of new medicines is a long and expensive process. Despite growing efforts in R&D over the last decades, attrition rate due to safety issues (especially cardiac and hepatic toxicity) remains a major challenge for the pharmaceutical industry. This may lead to market withdrawal or late stage halting of a drug development program. Consequently, early detection of toxicity issues is critical to avoid late-stage failures. To this end, development of predictive toxicology assays and models have become a strategic matter for drug makers...
November 21, 2017: Drug and Chemical Toxicology
Yasuhiro Tsubokura, Ryuichi Hasegawa, Sunao Aso, Toshio Kobayashi, Takayuki Koga, Satsuki Hoshuyama, Yutaka Oshima, Katsumi Miyata, Yuji Kusune, Takako Muroi, Naoki Hashizume, Yoshiyuki Inoue, Shozo Ajimi, Kotaro Furukawa
We have conducted animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade and Industry of Japan. Here we conducted a combined repeated-dose and reproductive/developmental toxicity screening test of benzene, 1,1'-oxybis-, tetrapropylene derivs. (BOTD). BOTD was administered to 9-week-old Crl:CD(SD) male and female rats by gavage at 0, 40, 200, or 1000 mg/kg/day. Males were treated for 42 days including mating period. Females were treated for 42-53 days through the premating, mating, pregnancy, and until Day 4 of lactation periods...
November 20, 2017: Drug and Chemical Toxicology
Jingyuan Xiong, Liantian Tian, Yongjie Qiu, Ding Sun, Hao Zhang, Mei Wu, Jintao Wang
Thyroid hormones are involved in many important physiological activities including regulation of energy metabolism, development of nervous system, maintenance of cerebral functions, and so on. Endocrine-disrupting chemicals (EDCs) that interfere with thyroid functions raise serious concerns due to their frequent misuse in areas where regulations are poorly implemented. In addition, chemicals that are originally regarded safe may now be considered as toxic with the development of life sciences. Malathion is an organophosphate insecticide that is widely applied and distributed in agricultural and residential settings...
November 16, 2017: Drug and Chemical Toxicology
Hyungjoo Kim, Sunhwa Oh, Myung Chan Gye, Incheol Shin
Nonylphenol polyethoxylates (NPEOs) are a major group of nonionic surfactants widely used in various detergents, cleaners, plastics, papers, and agro-chemical products. Nonylphenol (NP), which is a final degraded metabolite derived from NPEOs, has been reported as an endocrine disrupter, known to mimic or disturb reproductive hormone functions. Concern about the hazards of NP and NPEOs has generated legal restrictions and action plans worldwide. Considering the fact that NP and NPEOs are majorly used in the production of products such as detergents, shampoos, and cosmetics which frequently come into contact with the skin, we investigated the effects of NP and NPEOs on a human keratinocyte cell line (HaCaT)...
November 10, 2017: Drug and Chemical Toxicology
Selma Yaman, Ülkü Çömelekoğlu, Evren Değirmenci, Meryem İlkay Karagül, Serap Yalın, Ebru Ballı, Saadet Yıldırımcan, Metin Yıldırım, Adem Doğaner, Kasım Ocakoğlu
In spite of their widespread use, toxicity of silica nanoparticles (SiO2 NPs) to mammalian has not been extensively investigated. In the present study, it is aimed to investigate the effects and the mechanism of action of 20 nm sized SiO2 NPs on isolated uterine smooth muscle. A total number of 84 preparations of uterine strips were used in the experiments. Study was designed as four groups: group I (control), group II (0.2 mM SiO2 NPs), group III (0.4 mM SiO2 NPs) and group IV (0.8 mM SiO2 NPs). Spontaneous contractions were recorded using mechanical activity recording system...
November 8, 2017: Drug and Chemical Toxicology
Mariângela Spadoto, Ana Paula Erbetta Sueitt, Carlos Alexandre Galinaro, Tiago da Silva Pinto, Caroline Moço Erba Pompei, Clarice Maria Rispoli Botta, Eny Maria Vieira
Toxicities of bisphenol A (BPA) and nonylphenol (NP) to the neotropical freshwater cladocerans Ceriodaphnia silvestrii and Daphnia similis were studied under laboratory conditions. Acute exposures to BPA generated mean 48-h EC50 values of 14.44 (6.02-22.85) mg L(-1) for C. silvestrii and 12.05 (1.73-22.37) mg L(-1) for D. similis. When the organisms were exposed to acute doses of NP, mean 48-h EC50 values were 0.055 (0.047-0.064) mg L(-1) (C. silvestrii) and 0.133 (0.067-0.200) mg L(-1) (D. similis). Ceriodaphnia silvestrii was also tested in chronic bioassays, which resulted in mean 8-d IC25 values of 2...
November 8, 2017: Drug and Chemical Toxicology
Milad Vahidirad, Milad Arab-Nozari, Hamidreza Mohammadi, Ehsan Zamani, Fatemeh Shaki
Diazinon (Dz) is a widely used insecticide. It can induce nephrotoxicity and neurotoxicity via oxidative stress. Captopril, an angiotensin-converting enzyme inhibitor, is known for its antioxidant properties. In this study, we used captopril for ameliorating of Dz-induced kidney and brain toxicity in rats. Animals were divided into five groups as follows: negative control (olive oil), Dz (150 mg kg(-1)), captopril (60 and 100 mg kg(-1)) and positive control (N-acetylcysteine 200 mg kg(-1)) were injected intraperitoneally 30 min before Dz...
November 8, 2017: Drug and Chemical Toxicology
Majid Zeinali, Naser Tayebi Meybodi, Seyed Abdolrahim Rezaee, Houshang Rafatpanah, Hossein Hosseinzadeh
Chrysin (CH) is a natural flavone which possesses antioxidant, anti-cancer, and anti-inflammatory properties. The aim of the present study was to investigate the effects of CH on biochemical parameters, histopathological changes, and genotoxicity and hematological indices in diazinon (DZN)-induced toxicity in BALB/c mice. We induced sub-acute toxicity in mice using DZN (20 mg/kg/day) and treated them with CH at the 12.5, 25, and 50 mg/kg/day five times/week in 28 days. In our study, DZN increased lipid profile and liver function tests (LFTs) and creatinine (Cr) but decreased the red blood cell acetylcholinesterase (RBC-AChE) activity and glucose level...
November 2, 2017: Drug and Chemical Toxicology
Mohammad A Y Alqudah, Fahmi Y Al-Ashwal, Karem H Alzoubi, Mohammad Alkhatatbeh, Omar Khabour
Oxaliplatin is a platinum-based anticancer drug that has been shown to be genotoxic to the normal cells. Vitamin E is a potent antioxidant that may protect and enhance the repair of the damaged DNA. In this study, we aimed to evaluate the genotoxic effect of oxaliplatin on DNA by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in cultured human lymphocytes. We also attempted to explore the potential protective effect of vitamin E on chromosomal damage induced by oxaliplatin...
November 2, 2017: Drug and Chemical Toxicology
Elahe Esmaeelpanah, Bibi Marjan Razavi, Faezeh Vahdati Hasani, Hossein Hosseinzadeh
The neurotoxicity of acrylamide (ACR) monomer occurs through different mechanisms such as oxidative stress. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) are green tea catechins which are known as powerful antioxidants. In this study, we examined the possible protective effects of ECG and EGCG on ACR neurotoxicity in both in-vitro and in-vivo models. PC12 cells were exposed to different concentrations of ECG and EGCG. After 24 and 48 hours, ACR was added to the cells (IC50 = 4.85 mM) and cell viability was measured through MTT assay after 24 hours...
October 26, 2017: Drug and Chemical Toxicology
Ankita J Shah, Sivakumar Prasanth Kumar, Mandava V Rao, Himanshu A Pandya
Several studies documented the ameliorative effects of curcumin which plays a pivotal role in radical scavenging activities. It also participates in various cellular pathways and interacts with multiple targets. In the present study, we investigated the ameliorative effect of curcumin upon chromosomal genotoxicity induced by cyclosporine, an immunosuppressant, using in vitro approaches. A plausible mechanism of how curcumin mitigates the genotoxic implications of cyclosporine was ascertained using in silico tools...
October 26, 2017: Drug and Chemical Toxicology
Barbora Pastorková, Petr Illés, Zdeněk Dvořák
The aim of current study was to evaluate the effect of the most common anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) on the transcriptional activity of steroid and nuclear receptors. The activities of steroid receptors - progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), and nuclear receptors - vitamin D receptor (VDR), retinoid X receptor (RXR), retinoic acid receptor (RAR), pregnane X receptor (PXR), and thyroid receptor (TR) were assessed using either stable transfected luciferase gene reporter cell lines or transiently transfected cell lines...
October 26, 2017: Drug and Chemical Toxicology
Olumayowa O Igado, Jan Glaser, Mario Ramos-Tirado, Ezgi Eylül Bankoğlu, Foluso A Atiba, Ulrike Holzgrabe, Helga Stopper, James O Olopade
Moringa oleifera is reported to be a miracle plant, with positive effects on practically every system in the animal body. The methanolic extract of Moringa oleifera leaves was fractionated using liquid-liquid fractionation, column chromatography and preparative high-performance liquid chromatography (HPLC). Bioassay guided fractionation using Ferric Reducing Antioxidant Power (FRAP) was used to determine the fraction with the highest antioxidative power. Chemical structure was elucidated with nuclear magnetic resonance (NMR) spectroscopy...
September 19, 2017: Drug and Chemical Toxicology
Asuka Ito, Mostofa Jamal, Kiyoshi Ameno, Naoko Tanaka, Ayaka Takakura, Takanori Miki, Hiroshi Kinoshita
Carbon monoxide (CO) produces several neurological effects, including cognitive, mood, and behavioral disturbance. Glutamate is thought to play a particularly important role in learning and memory. Thus, the present study was aimed at investigating the local effect of CO on the glutamate level in the hippocampus of mice using in vivo reverse microdialysis. Mice were perfused with Ringer's solution (control) or CO (60-125 μM) in Ringer's solution into the hippocampus via microdialysis probe. Dialysate samples were collected every 20 min, and then analyzed with high-performance liquid chromatography coupled to an electrochemical detector...
September 4, 2017: Drug and Chemical Toxicology
M O Awodiran, A O Adepiti, K F Akinwunmi
The toxicity profile of medicinal plants is an important preclinical requirement in the development of phytomedicines. The cytotoxic and genotoxic effects of the leaf of Uvaria chamae P. Beauv (Annonaceae) and stem bark of Morinda lucida Benth (Rubiaceae) were investigated in order to provide information on their safety as antimalarial plants. The methanol extract of U. chamae and ethanol (70%) extract of M. lucida were separately orally administered (125, 250, and 750 mg/kg/day) to mice for 10 consecutive days...
August 31, 2017: Drug and Chemical Toxicology
Hayal Cobanoglu, Mahmut Coskun, Akin Çayir, Munevver Coskun
Antidepressants are drugs used for the treatment of many psychiatric conditions including depression. There are findings suggesting that these drugs might have genotoxic, carcinogenic, and/or mutagenic effects. Therefore, the present in vitro study is intended to investigate potential genotoxic and cytotoxic effects of the antidepressants escitalopram (selective serotonin reuptake inhibitor) and doxepin (Tricyclic antidepressant) on human peripheral lymphocytes cytokinesis-block micronucleus (CBMN), sister chromatid exchange (SCE), and single cell gel electrophoresis (alkaline comet assay) were used for the purpose of the study...
August 31, 2017: Drug and Chemical Toxicology
Birsen Aydın, Zülal Atlı Şekeroğlu, Vedat Şekeroğlu
Acrolein (AC), a highly reactive hazardous pollutant, poses serious threats to human health. Whey protein (WP) and conjugated linoleic acid (CLA) have beneficial health implications. We investigated the protective effects of WP and CLA against AC-induced toxicity in rats. The animals were orally gavaged with CLA (200 mg/kg/day), WP (200 mg/kg/day), AC (5 mg/kg/day), CLA + AC (200 + 5 mg/kg/day), and WP + AC (200 + 5 mg/kg/day) six days per week for 30 days. The oral administration of AC significantly induced oxidative stress by increasing thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCOs) levels and decreasing glutathione (GSH) level in the spleen, thymus, and polymorphonuclear leukocytes (PMNs)...
August 3, 2017: Drug and Chemical Toxicology
Aslı Uçar, Serkan Yılmaz, Şemsigül Yılmaz, Mustafa Sefa Kılıç
Stevia extracts are obtained from Stevia rebaudiana commonly used as natural sweeteners. It is ∼250-300 times sweeter than sucrose. Common use of stevia prompted us to investigate its genotoxicity in human peripheral blood lymphocytes. Stevia (active ingredient steviol glycoside) was dissolved in pure water. Dose selection was done using ADI (acceptable daily intake) value. Negative control (pure water), 1, 2, 4, 8 and 16 μg/ml concentrations which were equivalent to ADI/4, ADI/2, ADI, ADI × 2 and ADI × 4 of Stevia were added to whole-blood culture...
July 24, 2017: Drug and Chemical Toxicology
Tayyaba Ali, Muhammad Ismail, Farkhanda Asad, Asma Ashraf, Usman Waheed, Qaiser M Khan
To control agricultural pests and meet the increasing food demands, pesticides use has been increased substantially over time. Although pesticides are relatively specific to their targets, they can affect non-target organisms and are hazardous for the population around the application areas particularly to the individuals engaged in different types of agricultural activities. This situation is worse in developing and under-developed countries where personal protective equipment is merely used and regulatory guidelines are hardly practiced...
July 19, 2017: Drug and Chemical Toxicology
Mohammad Mahdi Vahedi, Davood Mahdian, Amir Hossein Jafarian, Mehrdad Iranshahi, Mahdi Esmaeilizadeh, Ahmad Ghorbani
Ferula gummosa is widely used in traditional medicine to treat a variety of ailments. This work evaluated the safety of F. gummosa root in pregnancy, lactation, and juvenile periods. This study was performed in three parts: (1) pregnant rats were received diet containing 0 (control), 150 , or 700 mg/kg of F. gummosa root during pregnancy; (2) Lactating rats were treated with diet containing the root (0, 150, or 700 mg/kg) during lactation period; (3) juvenile rats were received 4 weeks diet containing the root (0, 150, or 700 mg/kg)...
July 5, 2017: Drug and Chemical Toxicology
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