A review on the pharmacokinetic properties and toxicity considerations for chloroquine and hydroxychloroquine to potentially treat coronavirus patients.

The SARS-CoV-2 virus, caused a novel emerged coronavirus disease, is growing rapidly worldwide. Few studies have evaluated the efficacy and safety of Chloroquine (CQ), an old antimalarial drug, and Hydroxychloroquine (HCQ) in the treatment of COVID-19 infection. HCQ is derived from CQ by adding a hydroxyl group into it and is a less toxic derivative of CQ for the treatment of COVID-19 infection because it is more soluble. This article summarizes pharmacokinetic properties and toxicity considerations for CQ and HCQ, drug interactions, and their potential efficacy against COVID-19. The authors also look at the biochemistry changes and clinical uses of CQ and HCQ, and supportive treatments following toxicity occurs. It was believed that CQ and HCQ may provide few benefits to COVID-19 patients. A number of factors should be considered to keep the drug safe, such as dose, in vivo animal toxicological findings, and gathering of metabolites in plasma and/or tissues. The main conclusion of this review is that CQ and HCQ with considered to their ADMET properties has major shortcomings and fully irresponsible.

Effect of Antioxidants (ß-mercaptoethanol and Cysteamine) on Assisted Reproductive Technology In vitro.

INTRODUCTION: Oocyte Culture of Germinal Vesicle (GV) and its growth improves Assisted Reproductive Technology (ART) invitro and infertility. Inappropriate culture medium environment, low quality of oocytes, increase in Oxidative Stress (OS) events, Reactive Oxygen Species (ROS) and free radicals production are the main factors that result in unsuccessful Invitro Maturation (IVM) and decrease in reproduction. AIM: The present study was conducted with the aim to evaluate the effect of ß-mercaptoethanol (BME) and Cysteamine (CYS) on IVM improvement, embryo fertilization and development of blastocyst of mouse immature oocyte. MATERIALS AND METHODS: Oocytes were obtained from 4-6 weeks old Naval Medical Research Institute (NMRI) female mice, 48 hours after stimulation with Intraperitoneal (IP) injection of 10 IU Pregnant Mare Serum Gonadotropin (PMSG). GV oocyte with and without cumulus cells were isolated from ovaries and cultured in Tissue Culture Medium (TCM) 199 with availability of 100 µM of antioxidants (BME and CYS). After 24 hours, mature oocyte in metaphase II (MII) were fertilized with sperm in In vitro Fertilization (IVF) medium (T6) and evaluated for fetal development into blastocyst. RESULTS: BME and CYS could significantly (p<0.05) increase the rate of IVM and oocyte evolution, and embryo formation in medium culture. Furthermore, it is demonstrated that existence of Cumulus Oocyte Complexes (COC) significantly showed better IVM, fertilization and evolution trend as compared to oocytes without cumulus cover or Denuded Oocytes (DO), especially in TCM199 plus BME and CYS. So that the change in GV stage oocytes to MII (maturation rate), fertilization rates or 2PN formation, and two cell embryos formation or blastocyst development rate in the treatment group with addition of BME & CYS and COC was statistically significant as compared to the DO group (p-value < 0.0001). CONCLUSION: Both cellular and environmental factors could be important and involved in ART improvement.

Cytosolic and mitochondrial ROS: which one is associated with poor chromatin remodeling?

The aim of this study was to determine if there are any associations between impaired chromatin packaging and the origin of reactive oxygen species (ROS) production. Cytosolic ROS, mitochondrial ROS, DNA protamination, and apoptosis were evaluated with dichlorofluoresceindiacetate (DCFH-DA), dihydrorhodamine 123 (DHR123), chromomycin A3 (CMA3), and YO-Pro-1 (Y1)/propidium iodide (PI), respectively, by flow cytometry (FCM) in 40 infertile individuals. Percentages DCF+ and R123+ sperm were positively associated with percentage CMA3+ sperm and negatively associated with percentage apoptotic sperm. No correlation was observed between CMA3+ sperm and the percentage of apoptotic sperm. Under protamination of sperm is not associated with the origin of ROS production, but their relationship may suggest an association with general physiological dysfunction of sperm. Furthermore, under protamination does make sperm prone to apoptosis. Rather, it is likely that apoptosis is induced by ROS production. Considering that these conclusions are derived from correlative analyses, additional studies including an interventive approach are required.