Igor Koturbash

University of Arkansas for Medical Sciences | UAMS · Department of Environmental Health Sciences

Herbal dietary supplements have gained wide acceptance as alternatives to conventional therapeutic agents despite concerns regarding their efficacy and safety. In 2013, a spate of severe liver injuries across the United States was linked to the dietary supplement OxyELITE Pro-New Formula (OEP-NF), a multi-ingredient product marketed for weight loss...

The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice. Animals were gavaged with either 0, 246, 738, or 2460 mg/kg of CBD (acute toxicity, 24 h) or with daily doses of 0, 61.5, 184.5, or 615 mg/kg for 10 days (sub-acute toxicity). These doses were the allometrically scaled mouse equivalent doses (...

Methionine is an essential amino acid needed for a variety of processes in living organisms. Ionizing radiation (IR) depletes tissue methionine concentrations and leads to the loss of DNA methylation and decreased synthesis of glutathione. In this study, we aimed to investigate the effects of methionine dietary supplementation in CBA/CaJ mice after...

Cannabidiol (CBD) is the major non-psychotropic phytocannabinoid present in Cannabis sativa. In 2018, Congress designated certain C. sativa plant material as “hemp,” thus removing it from the DEA’s list of controlled substances. As a result, CBD-containing hemp extracts and other CBD products are now widely available and heavily marketed, yet their...

Despite promising preliminary biology, natural products isolation efforts may be confounded when the active compound is not isolated during bioassay-guided purification or classical pharmacognostic research investigations. A more rational isolation procedure connecting the polypharmacology of an herb to its individual constituents must be applied t...

Background Scholarly publications are important indicators of research productivity and investigator development in Centers of Biomedical Research Excellence (COBREs). However, no information is available to describe implementation and evaluation of writing development programs within COBREs. Therefore, this paper aimed to evaluate the first year o...

Botanical supplements, herbal remedies, and plant-derived products are used globally. However, botanical dietary supplements are rarely subjected to robust safety testing unless there are adverse reports in post-market surveillance. Botanicals are complex and difficult to assess using current frameworks designed for single constituent substances (e...

The Dietary Supplement Health and Education Act (DSHEA) of 1994 defined the FDA's statutory authority to regulate dietary supplement products as a category of food in the United States. As we celebrate 30 years post-DSHEA, it is important to reflect on its significance for public health, influence on the continuously evolving and expanding product...

Phenibut is a gamma aminobutyric acid derivative with activity at γ-aminobutyric acid (GABA)B, A and β-phenethylamine receptors. It was developed as a drug in the former Soviet Union to overcome anxiety and improve cognitive function in military personnel. In the last decade, it has made inroads into the European and U.S. markets, being marketed fo...

Cannabidiol (CBD) is a major phytocannabinoid from Cannabis sativa. It is currently widely available and widely used in the USA, but despite its rapid progress to market, the pharmacology and toxicology of both CBD and cannabidiol-rich cannabis extracts (CRCE) remain largely unknown. The goals of this study were to investigate the potential of a no...

Methionine is an essential amino acid critical for cell growth and survival. Preclinical evidence suggests a methionine restricted diet (MRD) sensitizes cancer to radiation therapy (RT), without significant adverse effects. However, this has never been evaluated in humans. The purpose of this pilot study was to evaluate the safety and feasibility o...

Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury. The current standard-of-care treatment for APAP hepatotoxicity, N-acetyl-l-cysteine, is highly effective when administered early after overdose, but loses efficacy in later-presenting patients. As a result, there is interest in the identification of new treatments...

Astronauts in space are subject to continuous exposure to ionizing radiation. There is concern about the acute and late-occurring adverse health effects that astronauts could incur following a protracted exposure to the space radiation environment. Therefore, it is vital to consider the current tools and models used to describe and study the organi...

Climate change presents multiple challenges to rural communities. Here, we investigated the toxicological potential of the six types of particulate matter most common to rural Arkansas: soil, road, and agricultural dusts, pollen, traffic exhaust, and particles from biomass burning in human small airway epithelial cells (SAECs). Biomass burning and...

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse hea...

e15087 Background: Methionine is an amino acid necessary for cell growth and survival. Normal cells can tolerate methionine deficiency, but most cancer cells are methionine auxotrophs, requiring dietary intake since they cannot synthesize it. In vitro, methionine deficiency causes cancer cells to undergo cell cycle arrest and cell death, and in viv...

Purpose: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current s...

Methylsulfonylmethane (MSM), a natural organosulfur compound, is a popular dietary supplement sold both as a single product and as a constituent of multi-ingredient products. It has been postulated that MSM may serve as a donor for methyl groups for various cellular processes; however, studies have yet to demonstrate this. Therefore, the goal of th...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the COVID-19 pandemic that can lead to severe respiratory distress requiring hospitalization and can be fatal. Media have reported that various dietary supplements (DS) or their combination with different medications can prevent infection or decrease...

Dietary supplements (DS) constitute a widely used group of products comprising vitamin, mineral, and botanical extract formulations. DS of botanical or herbal origins (HDS) comprise nearly 30% of all DS and are presented on the market either as single plant extracts or multi-extract-containing products. Despite generally safe toxicological profiles...

Purpose: Nuclear weapons testing in the northern Marshall Islands between 1946 and 1958 resulted in ionizing radiation (IR) exposure of the thousands of Marshallese. Furthermore, numerous islands were contaminated by radioactive fallout. Significant increases in cancer and metabolic syndrome incidences have been reported among Marshallese, and pot...

Ionizing radiation (IR) is a significant contributor to the contemporary market of energy production and an important diagnostic and treatment modality. Besides having numerous useful applications, it is also a ubiquitous environmental stressor and a potent genotoxic and epigenotoxic agent, capable of causing substantial damage to organs and tissue...

Both cell and animal studies have shown that complete or partial deficiency of methionine inhibits tumor growth. Consequently, the potential implementation of this nutritional intervention has recently been of great interest for the treatment of cancer patients. Unfortunately, diet alteration can also affect healthy immune cells such as monocytes/m...

Background: and purpose. Identification of appropriate dietary strategies for prevention of weight and muscle loss in cancer patients is crucial for successful treatment and prolonged patient survival. High-protein oral nutritional supplements decrease mortality and improve indices of nutritional status in cancer patients; however, high-protein die...

Cannabidiol (CBD) is a biologically active, non-psychotropic component of Cannabis sativa whose popularity has grown exponentially in recent years. Besides a wealth of potential health benefits, ingestion of CBD poses risks for a number of side effects, of which hepatotoxicity and CBD/herb-drug interactions are of particular concern. Here, we inves...

Cannabidiol (CBD) is a non-psychotropic constituent of Cannabis sativa that has grown in popularity during the last decade. CBD is the active component of EPIDIOLEX®, a U.S. Food and Drug Administration (FDA)-approved drug designed for the treatment of drug-resistant pediatric epileptic seizures associated with several rare syndromes. Furthermore,...

The proliferation in the last few years of cannabidiol (CBD)-containing products in the U.S. markets has been greatly accelerated by changes in the regulatory environment, and by perceptions of their health benefits and presumed safety. The result has been aggressive marketing of many types of products, some of dubious quality, making or implying d...

Objectives Cannabidiol (CBD) is the major non-psychotropic phytocannabinoid present in Cannabis sativa. In 2018, Congress designated select C. sativa cultivars as “hemp” removing them from the DEA's list of controlled substances. As a result, CBD-containing hemp extracts and other CBD products are now widely available and heavily marketed, yet thei...

Objectives Green tea extracts (GTEs) are common ingredients among dietary supplements marketed for weight loss and weight management. However, GTEs and their various catechin polyphenols have also been linked to a number of hepatotoxicity cases. Methods The purpose of this study was to investigate, using various mouse models, the hepato- and cardi...

The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg...

Cardiovascular disease constitutes an important threat to humans after space missions beyond the Earth's magnetosphere. Epigenetic alterations have an important role in the etiology and pathogenesis of cardiovascular disease. Previous research in animal models has shown that protons and 56Fe ions cause long-term changes in DNA methylation and expre...

The main purpose of this study was to investigate the hepatotoxic potential and effects on the gut microbiome of decaffeinated green tea extract (dGTE) in lean B6C3F1 mice. Gavaging dGTE over a range of 1X–10X mouse equivalent doses (MED) for up to two weeks did not elicit significant histomorphological, physiological, biochemical or molecular alte...

Purpose: Astronauts traveling beyond low-Earth orbit will be exposed to high linear-energy transfer charged particles. Because there is concern about the adverse effects of space radiation on the cardiovascular system, this study assessed cardiac function and structure and immune cell infiltration in a mouse model of charged-particle irradiation....

Purpose. Growing rates of metabolic syndrome and associated obesity warrant the development of appropriate animal models for better understanding of how those conditions may affect sensitivity to IR exposure. Materials and Methods. We subjected male NZO/HlLtJ mice, a strain prone to spontaneous obesity and diabetes, to 0, 5.5, 6.37, 7.4 or 8.5 Gy (...

Methionine dependency describes the characteristic rapid in vitro death of most tumor cells in the absence of methionine. Combining chemotherapy with dietary methionine deprivation (MDD) at tolerable levels has vast potential in tumor treatment; however, it is limited by MDD-induced toxicity during extended deprivation. Recent advances in imaging a...

In addition to the generally accepted potential of ionizing radiation to cause DNA damage, its capability to target the cellular epigenome has become increasingly evident. Epigenetics unifies the chemical marks and molecules that collectively facilitate the proper reading of genetic material. Among the epigenetic mechanisms of regulation, methylati...

Nearly 50% of all cancer patients undergo radiotherapy. Up to 70% of patients develop acute radiation syndrome (ARS) and can be associated with specific organ systems, such as the gastrointestinal system . ARS is the single main factor limiting dose and duration of irradiation (IR). IR causes global DNA hypomethylation and DNA double-strand breaks...

Ionizing radiation is a valuable tool in many spheres of human life. At the same time, it is a genotoxic agent with a well-established carcinogenic potential. Progress achieved in the last two decades has demonstrated convincingly that ionizing radiation can also target the cellular epigenome. Epigenetics is defined as heritable changes in the expr...

It is becoming increasingly recognized that Long Interspersed Nuclear Element, 1 (LINE-1), the most ubiquitous repetitive element in the mammalian genomes, plays an important role in the pathogenesis of disease and in the response to exposure to environmental stressors. Ionizing radiation is a known genotoxic stressor, but it is capable of targetin...

MicroRNAs (miRNAs) are short regulatory RNAs that are involved in various biological processes that regulate gene expression posttranscriptionally. Changes in miRNA expression can be detected in many physiological and pathological events, such as liver injury. Drug induced liver injury is a life threatening condition that frequently requires organ...

Background: Methionine, a central molecule in one-carbon metabolism, is an essential amino acid required for normal growth and development. Despite its importance to biological systems, methionine is toxic when administered at supra-physiological levels. The aim of this study was to investigate the effects of short-term methionine dietary modulati...

Background: Space travel is associated with continuous low dose rate exposure to high linear energy transfer (LET) radiation. Pathophysiological manifestations after low dose radiation exposure are strongly influenced by non-cytocidal radiation effects, including changes in the microbiome and host gene expression. Although the importance of the gu...

The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions and translating exposures into...

Purpose Space travel is associated with an exposure to low-dose rate ionizing radiation and the microgravity environment, both of which may lead to impairments in cardiac function. We used a mouse model to determine short- and long-term cardiac effects to simulated microgravity (hindlimb unloading; HU), continuous low-dose rate γ-irradiation, or a...

Antioxidant protein content in mouse heart following HU, γ irradiation or combined HU + γ irradiation. Immunoblot analysis was used to determine protein content of a.) Nrf2 4 months, b.) Nrf2 9 months c.) Catalase 4 months, and d.) Catalase 9 months following HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or combined HU + γ irradiation. All p...

SAM concentration in mouse heart following HU, γ irradiation or combined HU + γ irradiation. HPLC was utilized to determine methionine concentration in mouse heart a.) 7 days, b.) 1 month, or c.) 9 month after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: CTL for all time p...

Pro-collagen III mRNA content in mouse heart following HU, γ irradiation or combined HU + γ irradiation relative to control 18s mRNA content. rt-PCR was used to determine pro-collagen III fold change 9 months after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: all groups n...

4-HNE protein content in mouse heart following HU, γ irradiation or combined HU + γ irradiation. Immunoblot analysis was used to determine 4-HNE protein content a.) 4 months and b.) 9 months after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: CTL for 4 month time-point n =...

SAH concentration in mouse heart following HU, γ irradiation or combined HU + γ irradiation. HPLC was utilized to determine methionine concentration in mouse heart a.) 7 days, b.) 1 month, or c.) 9 month after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: CTL for all time p...

α-SMC actin protein content in mouse heart following HU, γ irradiation or combined HU + γ irradiation. Immunoblot analysis was used to determine protein content of a.) α-SMC actin 4 months and b.) α-SMC actin 9 months following HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or combined HU + γ irradiation. All proteins normalized to GAPDH. Imm...

GSSG concentration in mouse heart following HU, γ irradiation or combined HU + γ irradiation. HPLC was utilized to determine methionine concentration in mouse heart a.) 7 days, b.) 1 month, or c.) 9 month after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: CTL for all time...

Methionine concentration in mouse heart following HU, γ irradiation or combined HU + γ irradiation. HPLC was utilized to determine methionine concentration in mouse heart a.) 7 days, b.) 1 month, or c.) 9 month after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: CTL for all...

The data used in the preparation of this manuscript. (XLSX)

GSH concentration in mouse heart following HU, γ irradiation or combined HU + γ irradiation. HPLC was utilized to determine methionine concentration in mouse heart a.) 7 days, b.) 1 month, or c.) 9 month after a 21 day exposure to HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or a combined HU + γ irradiation. Sample sizes: CTL for all time p...

Antioxidant protein content in mouse heart following HU, γ irradiation or combined HU + γ irradiation. Immunoblot analysis was used to determine protein content of a.) MnSOD 4 months, b.) MnSOD 9 months c.) GPX1/2 4 months, and d.) GPX1/2 9 months following HU, γ irradiation (57Co: 0.01 cGy/h; 0.04 Gy total), or combined HU + γ irradiation. All pro...

Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons are the major repetitive elements in mammalian genomes. LINE-1s are well-accepted as driving forces of evolution and critical regulators of the expression of genetic information. Alterations in LINE-1 DNA methylation may lead to its aberrant activity and are reported in virtually all hum...

Ionizing radiation (IR) is a ubiquitous component of our environment and an important tool in research and medical treatment. At the same time, IR is a potent genotoxic and epigenotoxic stressor, exposure to which may lead to negative health outcomes. While the genotoxocity is well described and characterized, the epigenetic effects of exposure to...

Identification of sensitive and novel biomarkers or endpoints associated with toxicity and carcinogenesis is of a high priority. There is increasing interest in the incorporation of epigenetic and metabolic biomarkers to complement apical data; however, a number of questions, including the tissue specificity, dose-response patterns, early detection...

Free eprints link: http://www.tandfonline.com/eprint/5BNrrHkWrMsUUtDDHXbu/full Purpose: Ionizing radiation (IR) is a ubiquitous environmental stressor with genotoxic and epigenotoxic capabilities. Terrestrial IR, predominantly a low-linear energy transfer (LET) radiation, is being widely utilized in medicine, as well as in multiple industrial ap...

Ionizing radiation (IR) induces numerous stable and unstable chromosomal aberrations. Unstable aberrations, where chromosome morphology is substantially compromised, can easily be identified by conventional chromosome staining techniques. However, detection of stable aberrations, which involve exchange or translocation of genetic materials without...

Exposure to particulate matter (PM) is a major world health concern, which may damage various cellular components, including the nuclear genetic material. To assess the impact of PM on nuclear genetic integrity, structural chromosomal aberrations are scored in the metaphase spreads of mouse RAW264.7 macrophage cells. PM is collected from ambient ai...