Morin improves Bisphenol-A-induced toxicity in the rat testicular mitochondria and sperms.

OBJECTIVE: The present study aimed to examine the ameliorative effects of Morin (MRN) on Bisphenol-A (BPA)-induced oxidative stress in testicular mitochondria and sperm quality of rats. METHODS: BPA and MRN (25, 50, and 100 µM) were given to the spermatozoa and testicular tissue mitochondria. The sperm quality, mitochondrial viability, and MMP (mitochondrial membrane potential) were examined. Superoxide dismutase, CAT (catalase), malondialdehyde, and reactive oxygen species (ROS) levels of rat testicular mitochondria were measured. RESULTS: BPA raised mitochondrial oxidative stress biomarkers, whereas antioxidant acclivity and MMP were significantly lowered. BPA significantly lowered the normality, viability, and motility of the sperms. MRN dose-dependently lowered oxidative stress of the mitochondria, raised MMP, as well as improved the percentage of abnormality, motility, and viability of the sperms. CONCLUSIONS: These data demonstrated that MRN dose-dependently attenuated BPA-induced mitochondrial damage and improved sperm quality by preventing oxidative stress.

Myricetin loaded in solid lipid nanoparticles induces apoptosis in the HT-29 colorectal cancer cells via mitochondrial dysfunction.

BACKGROUND: Among the flavonoids, Myricetin (MCN) has negligible side effects and anti-cancer properties. However, the therapeutic potential of MCN has been limited mainly by its low bioavailability. Nanocarriers improve the bioavailability and stability of flavonoids. The toxic effects of MCN loaded in solid lipid nanoparticles (MCN-SLNs) on the HT-29 human colorectal cancer cells were investigated in this study. METHODS AND RESULTS: HT-29 cells were exposed to the 30 µmol MCN or MCN-SLNs for 24 h. Colony formation, cell viability, apoptosis, and expression of the Bax, Bcl-2, and AIF (apoptosis-inducing factor) have been investigated. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation were also measured. The MCN-SLNs with appropriate characteristics and a slow sustained MCN release until 48 h made. MCN-SLNs could diminish colony numbers and survival of the HT-29 cells. The apoptosis index of MCN-SLNs-treated cells significantly increased compared to the free MCN (p < 0.001). The expression of Bax and AIF were elevated (p < 0.01 and p < 0.001, respectively) while Bcl-2 expression was decreased in MCN-SLNs treatment (p < 0.05). Moreover, MCN-SLNs significantly enhanced the ROS formation and reduced MMP compared to the free MCN-treated cells (p < 0.01). CONCLUSIONS: The SLN formulation of MCN can effectively induce colon cancer cell death by raising ROS formation and activating the apoptosis process.

Liver histopathological alteration and dysfunction after bisphenol A administration in male rats and protective effects of naringin.

OBJECTIVE: Bisphenol A (BPA) is an organic synthetic compound, often used in manufacturing polycarbonate plastics. Researches have shown the role of BPA as an endocrine disruptor. The present study intended to evaluate the hepatoprotective properties of naringin, an active flavanone glycoside present in many citrus fruit, against hepatotoxicity induced by BPA. MATERIALS AND METHODS: Male Wistar rats were orally treated with 50 mg/kg BPA for 30 consecutive days for induction of toxicity and 40, 80 and 160 mg/kg naringin for the same period along with BPA or alone. RESULTS: This study demonstrated that BPA significantly increased serum levels of triglyceride, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), lipid peroxidation, and aspartate aminotransferase (AST) and significantly reduced catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity, glutathione (GSH) and caused periportal inflammation and microvesicular steatosis in rat tissue. However, BPA did not change serum levels of high-density lipoprotein-cholesterol (HDL-C), total cholesterol, alanine aminotransferase (ALT), or low-density lipoprotein-cholesterol (LDL-C). Furthermore, the results displayed that administration of 80 and 160 mg/kg naringin improved hepatotoxicity and altered lipid peroxidation level, serum values of triglyceride and liver enzymes, and oxidative stress factors that were induced by BPA. The effect of two doses of 80 and 160 mg/kg naringin was more noticeable than that of dose 40 mg/kg. CONCLUSION: The findings suggested the protective effects of naringin against BPA-induced hepatotoxicity via ameliorating liver histopathological alteration, suppressing oxidative stress and lipid-lowering properties.

Taurine attenuates valproic acid-induced hepatotoxicity via modulation of RIPK1/RIPK3/MLKL-mediated necroptosis signaling in mice.

Valproic acid (VPA) is known as a common drug in seizure and bipolar disorders treatment. Hepatotoxicity is the most important complication of VPA. Taurine (Tau), an amino acid, has antioxidant effects. The present research was conducted to evaluate the protective mechanisms of Tau on VPA-induced liver injury, especially focusing on the necroptosis signaling pathway. The sixty-four male NMRI mice were divided into eight groups with eight animals per each. The experiment groups pretreated with Tau (250, 500, 1000 mg/kg) and necrostatine-1 (Nec-1, 1.8 mg/kg) and then VPA (500 mg/kg) was administered for 14 consecutive days. The extent of VPA-induced hepatotoxicity was confirmed by elevated ALP (alkaline phosphatase), AST (aspartate aminotransferase), ALT (alanine aminotransferase) levels, and histological changes as steatosis, accumulation of erythrocytes, and inflammation. Additionally, VPA significantly induced oxidative stress in the hepatic tissue by increasing ROS (reactive oxygen species) production and lipid peroxidation level along with decreasing GSH (glutathione). Hepatic TNF-α (tumor necrosis factor) level, mRNA and protein expression of RIPK1 (receptor-interacting protein kinase 1), RIPK3, and MLKL (mixed lineage kinase domain-like pseudokinase) were upregulated. Also, the phosphorylation of MLKL and RIPK3 increased in the VPA group. Tau could effectively reverse these events. Our data suggest which necroptosis has a key role in the toxicity of VPA through TNF-α-mediated RIPK1/RIPK3/MLKL signaling and oxidative stress. Our findings suggest that Tau protects the liver tissue against VPA toxicity via inhibiting necroptosis signaling pathway mediated by RIPK1/RIPK3/MLKL and suppressing oxidative stress, and apoptosis.

Allium jesdianum Extract Induces Oxidative Stress and Necroptosis in Human Colorectal Cancer (HT-29) Cell Line

Abstract This study aimed to evaluate the toxic impact of hydro-alcoholic Allium jesdianum extract (AJE) on the growth of HT-29 human colorectal cancer cell line. Phytochemical analysis using gas chromatography and mass spectroscopy (GCMS) was done to determine the bioactive components of AJE. HT-29 cells exposed to 0 (control), 25, 50, and 100 ��g/mL of AJE for 48 hours. Cell survival, colony numbers, flow cytometry, oxidative stress, and gene expression were examined to evaluate the toxic impacts of the AJE. Twelve different phyto-constituents with peak areas were determined by the GCMS analysis. The major compounds were Allicin and α-Pinene. AJE considerably reduced the viability and colony numbers of the HT-29 cells. The AJE concentration-dependently increased necrosis, but not apoptosis in the HT-29 cells. AJE upregulated the expression of necroptosis-associated genes including RIPK1, RIPK3, and MLKL in a concentration-dependent manner. AJE also dose-dependently enhanced MDA contents and reactive oxygen species (ROS) level and diminished antioxidant enzyme level in the HT-29 cells. These data collectively indicated that AJE prevented the growth of the HT-29 cells by inducing oxidative stress, and activation necroptosis signaling pathways.

In vitro anticancer activity of Scrophularia amplexicaulis extracts on MCF-7 and WEHI-164 cell line.

Scrophularia amplexicaulis is an Iranian endemic plant belonging to the Scrophulariaceae family, which is used in traditional medicine to treat many diseases. The aim of this study was to evaluate the in vitro anticancer activity of S. amplexicaulis extracts against human breast carcinoma (MCF-7) and mouse fibrosarcoma (WEHI-164) cell lines. The ground aerial parts of S. amplexicaulis were soxhlet-extracted with n-hexane, dichloromethane and methanol. MTT assay exhibited that dichloromethane and methanol extracts remarkbly inhibited the growth of MCF-7 and WEHI-164 cancer cells in a dose-and time-dependent manner with little cytotoxicity on normal cell line HUVEC. Cell death ELISA, TUNEL assay, and the cleavage of poly ADP-ribose polymerase (PARP) uncovered that the cytotoxic effects of dichloromethane and methanol extracts were attributed to apoptosis in cancerous cells. Furthermore, quantitative real-time PCR revealed significant increases in the mRNA expression levels of p-53, caspase-3, caspase-9, Bax, and also a decrease in Bcl-2 expression. These results suggested that the extracts mainly induced apoptosis via a mitochondria-mediated intrinsic pathway. Notably, dichloromethane extract had higher cytotoxic and apoptotic activities than that of methanol extract, against both cancer cell lines, particularly MCF-7 cells. Our results indicate that S. amplexicaulis may serve as a promising source of potent agents for the treatment of human cancers.

Correction to: The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach.

The article "The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach", written by Seyed Farzad Hosseini · Mehdi Forouzesh · Mohsen Maleknia · Samira Valiyari · Mahmood Maniati · Azin Samimi, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 25th July 2020 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 29th July 2020 to © Springer Science+Business Media, LLC, part of Springer Nature 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.

Effects of Wharton's jelly mesenchymal stem cells-derived secretome on colon carcinoma HT-29 cells.

Secreted factors (secretome) of Wharton's jelly mesenchymal stem cells (WJMSCs) have therapeutic impacts. This study was conducted to investigate the impact of WJMSCs-derived secretome (WJMSCs-Se) in apoptosis and the growth of HT-29 cells. HT-29 cells treated with 25 or 50 µg/mL WJMSCs-Se for 24 h. Colony formation and MTT test was used to assess the proliferation and cytotoxicity of the HT-29 cells. Annexin V/PI staining was done for the assessment of apoptosis. The mRNA expression of important apoptosis-related genes was also examined. In the WJMSCs-Se-treated HT-29 cells, colony numbers and viability percentages were significantly reduced in a concentration-dependent manner. Apoptotic and necrotic indexes of WJMSCs-Se-treated HT-29 cells considerably enhanced in comparison to the control. The Caspase-9 and -3 activities were significantly increased in the WJMSCs-Se-exposed HT-29 cells. The mRNA expression of Caspase-9, Caspase-3, and Bax/ Bcl-2 ratio was considerably elevated in the WJMSCs-Se-treated HT-29 cells. Caspase-8 activity and expression of the p53 gene were not affected by the WJMSCs-Se. Taken together, we concluded that WJSCs-Se significantly prevented cell growth and enhanced colon cancer cell death in a concentration-dependent manner mainly through the intrinsic apoptotic pathway.

The Molecular Mechanism of Aluminum Phosphide poisoning in Cardiovascular Disease: Pathophysiology and Diagnostic Approach.

Nowadays, poisoning with metal phosphides, especially aluminum phosphide (ALP), is one of the main health threats in human societies. Patients suffer from significant complications due to this type of poisoning, and the heart is one of the main organs targeted by ALP. Therefore, in this study, we discussed the effect of phosphine on cardiac function. This study is based on data obtained from PubMed, between 2002 and 2020. The key keywords included "Aluminum phosphide," "Oxidative Stress," "Mitochondria," "Cardiovascular disease," and "Treatment." The results showed that ALP produced reactive oxygen species (ROS) due to mitochondrial dysfunction. ROS production leads to red blood cell hemolysis, decreased ATP production, and induction of apoptosis in cardiomyocytes, which eventually results in cardiovascular disease. Since ALP has the most significant effect on cardiomyocytes, the use of appropriate treatment strategies to restore cell function can increase patients' survival.

The role of molecular mechanism of Ten-Eleven Translocation2 (TET2) family proteins in pathogenesis of cardiovascular diseases (CVDs).

Cardiovascular disease (CVD) is one of the most common diseases worldwide. The underlying pathogenesis of the disease has not yet been determined, but many factors have been identified. Tet methylcytosine dioxygenase 2 (TET2) is one of the epigenetic factors involved in regulating many genes. Therefore, based on the studies shown, this factor plays an important role in preventing the occurrence of CVD. TET2 has been shown to increase angiogenesis by expressing Robo4. It also increases the activity of Matrix metalloproteinases (MMPs) and stimulates the secretion of Vascular endothelial growth factor angiogenesis. On the other hand, it has been shown that TET2 regulates the expression of several genes and the development of the heart during the embryonic period due to its oxygenating role. TET2 has been shown to regulates the expression of the genes such as Ying Yang1 (YY1), Sox9b, Inhbaa and many other genes that ultimately lead to the differentiation of cardiomyocytes. On the other hand, it has been shown that some Long non coding RNA and MicroRNAs reduce TET2 expression and CVD. Finally, it is concluded that inducing TET2 expression can be a good therapeutic strategy to prevent or improve CVD.

The Dual Role of ROS in Hematological Malignancies: Stem Cell Protection and Cancer Cell Metastasis.

BACKGROUND AND OBJECTIVE: Reactive oxygen species (ROS) play crucial role in hematopoiesis, regulation of differentiation, self-renewal, and the balance between quiescence and proliferation of hematopoietic stem cells (HSCs). The HSCs are a small population of undifferentiated cells that reside in the bone marrow (BM) and can undergo self-renewal by giving rise to mature cells. METHODS: Relevant literature was identified through a PubMed search (2000-2019) of English-language papers using the following terms: reactive oxygen species, hematopoietic stem cell, leukemic stem cell, leukemia and chemotherapy. RESULTS: HSCs are very sensitive to high levels of ROS and increased production of ROS have been attributed to HSC aging. HSC aging induced by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration. In addition, the elevated ROS levels might even trigger differentiation of Leukemic stem cells (LSCs) and ROS may be involved in the initiation and progression of hematological malignancies, such as leukemia. CONCLUSION: Targeting genes involved in ROS in LSCs and HSCs are increasingly being used as a critical target for therapeutic interventions. Appropriate concentration of ROS may be an optimal therapeutic target for treatment of leukemia during chemotherapy, but still more studies are required to better understanding of the of ROS role in blood disorders.

Protective effect of naringin against BPA-induced cardiotoxicity through prevention of oxidative stress in male Wistar rats.

Bisphenol A (BPA), which is an applied endocrine disrupting chemical in industry for producing epoxy resins and polycarbonate plastics and naringin, is an active flavanone glycoside of grapefruit and many citrus fruits. The present study evaluated the protective effect of naringin against cardiotoxicity induced by BPA. Male Wistar rats were divided into six groups. Control group received oral olive oil; and BPA group orally were administrated 50 mg/kg of BPA for 30 d consecutively to induce toxicity. 40, 80, and 160 mg/kg of naringin were orally administered for 30 consecutive, along with BPA. Naringin group orally received 160 mg/kg of naringin for 30 d consecutively. Animals were sacrificed and their biochemical, histological, and oxidative stress parameters were measured 24 h after the last treatment. Heart injury was induced by BPA as an evidence with a significant increase in levels of aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, triglyceride, lipid peroxidation, and a significant decrease in levels of glutathione, superoxide dismutase, catalase, and glutathione peroxidase and triggered myocardial disorganization, myofibrillar loss, congestion of red blood cells, and the inflammation. However, there were not any changes in the total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and alanine aminotransferase. Moreover, our results indicated that administering 80 and 160 mg/kg of naringin significantly altered all examined endpoints that were induced by BPA. Both concentrations of 80 and 160 mg/kg of naringin were more effective than 40 mg/kg. These findings indicated that naringin had a protective effect against cardiotoxicity induced by BPA through lipid-lowering properties, antioxidant activity, and suppressed lipid peroxidation.

Evaluation of the Protective Effects of Doxycycline on Acetaminophen-Induced Hepatotoxicity in Mice.

Acetaminophen (APAP) toxicity threatens human health due to increased mortality associated with its overdose. Doxycycline (DC) because of its properties such as antioxidant and anti-inflammatory can be a good therapeutic strategy to treat the acute toxicity induced by APAP. Male mice were divided into six groups in two periods of 3 h and 24 h as normal saline, APAP 400 mg/kg, DC 100 mg/kg and groups treated by 25, 50 and 100 mg/kg DC just before APAP, respectively. At the end of the 3 h and 24 h periods, the hepatic index, biochemical parameters including serum aspartate transaminase (AST) and alanine transaminase (ALT) activity and hepatic catalase activity, glutathione (GSH) and malondialdehyde (MDA) levels in liver and histopathological changes were evaluated. The results indicated that DC had no apparent effect on the hepatic index but significantly normalized the level of biochemical parameters and reduced APAP induced liver damage. Overall, it could be concluded that DC can inhibit or resolve harmful effects of APAP through antioxidant and anti-inflammatory properties. However, more studies are needed to understand exact mechanism of DC and its application for clinical use.

High fat diet deteriorates the memory impairment induced by arsenic in mice: a sub chronic in vivo study.

Both arsenic (As) and obesity are associated with brain disorders. However, long term studies to evaluate their concomitant adverse effects on the brain functions are lacking. Present study was conducted to evaluate the long term co-exposure of As and high fat diet (HFD) on memory and brain mitochondrial function in mice. Male mice were randomly divided into 7 groups fed with HFD or ordinary diet (OD) and instantaneously exposed to As (25 or 50 ppm) in drinking water for, 4, 8, 12, 16 or 20 weeks. Step-down passive avoidance method was used for memory assessment and post exposure various parameters including mitochondrial damage, level of reactive oxygen species (ROS), malondialdeid (MDA) and glutathione (GSH) were determined. Results indicated that the retention latency decreased in As (25 and 50 ppm) and HFD received mice after 12 and 16 weeks respectively. Same results were observed at significantly shorter duration (8th week) when As was administered along with HFD as compared to control group. In the HFD alone fed mice increased the mitochondrial membrane damage, levels of ROS and MDA were observed while GSH contents decreased significantly. Concomitant administration of HFD and As amplified those mentioned toxic effects (p < 0.001). In conclusion, our findings demonstrated that the simultaneous HFD and As impaired memory at least three times more than exposing each one alone. These toxic effects could be due to the mitochondria originated oxidative stress along with the depleted antioxidant capacity of the brain of mice.

Microarray analysis of apoptosis gene expression in liver injury induced by chronic exposure to arsenic and high-fat diet in male mice.

Rapid growth in the incidence of liver disease is largely attributable to lifestyle and environmental contaminants, which are often overlooked as the leading causes of this problem. Thus, the possible contribution of arsenic (As) to high-fat diet (HFD)-induced liver damage was examined via microarray analysis. To perform this experiment, a total number of 40 healthy adult male NMRI mice (22-30 g) were used. To this end, these animals were randomly assigned to four groups of 10. Oxidative stress and histopathological parameters were also evaluated in the liver of the mice exposed to a minimally cytotoxic concentration of As (50 ppm) in drinking water while being fed with a HFD for 20 weeks. Subsequently, apoptosis gene expression profiling was utilized via real-time (RT) PCR array analysis. The results showed that As had increased the amount of HFD-induced liver damage and consequently amplified changes in oxidative stress factors, histopathological parameters, as well as apoptosis pathway genes. Investigating the expression profile of apoptosis pathway genes similarly revealed that caspase-8, as a main upstream contributor to the apoptosis pathway, might play an important role in the induction of apoptosis generated by As and HFD. Ultimately, this study highlighted that As in drinking water could increase sensitivity in mice to HFD-induced liver disease through strengthening apoptosis pathway.

Efficiency of naringin against reproductive toxicity and testicular damages induced by bisphenol A in rats.

OBJECTIVES: Bisphenol A (BPA) as a synthetic compound is applied in many plastic industries. BPA has been reported to have endocrine-disrupting feature with cytotoxic effects. The study aimed to evaluate the efficiency of Naringin against testicular toxicity induced by BPA in adult rats. MATERIALS AND METHODS: The animals were assigned into six groups of control, BPA-treated (50 mg/kg), BPA+Naringin-administrated (40, 80, 160 mg/kg) and Naringin-treated (160 mg/kg) for 30 days. At the end of experiments, testicular weight, total testicular protein, epididymal sperm count, testicular enzymes, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and estradiol, testicular enzymatic and non-enzymatic antioxidants and histopathology of testis tissue were evaluated by their own methods. RESULTS: The results showed a reduction in testicular weight, total testicular protein, epididymal sperm count, testicular enzymes (alkaline phosphatase and lactate dehydrogenase) and decrease in the serum TSH, LH, testosterone and estradiol in BPA-administrated rats. Furthermore, BPA reduced the enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in testis tissue. Also, BPA caused an induction in lipid peroxidation and increase in reactive oxygen species levels, whereas it decreased the glutathione content of testis tissue. Histological findings exhibited seminiferous tubules vacuoles, atrophy and separation of the germinal epithelium in BPA-administrated rats. Oral administration of Naringin along with BPA normalized the biochemical, morphological and histological changes and reduced the testicular toxic condition. CONCLUSION: These results demonstrated that Naringin significantly managed male reproductive toxicity by antioxidant capabilities, preventing morphological modifications and escalating defense mechanism, thereby reducing oxidative stress from BPA-induced damage.

Role of bone marrow adipocytes in leukemia and chemotherapy challenges.

Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature was identified through a PubMed search (2000-2018) of English-language papers using the following terms: leukemia, adipocyte, leukemic stem cell, chemotherapy, and bone marrow. Findings suggest the striking interplay between leukemic cells and adipocytes to create a unique microenvironment supporting the metabolic demands and survival of leukemic cells. Based on these findings, targeting lipid metabolism of leukemic cells and adipocytes in combination with standard therapeutic agents might present novel treatment options.

Protective Effect of Naringin on Bisphenol A-Induced Cognitive Dysfunction and Oxidative Damage in Rats.

Bisphenol A (BPA) is one of the highest volume chemicals produced worldwide, which is used in many plastic industries. The present study aimed to evaluate the effect of BPA on cognitive functions and oxidative stress, and determine whether the naringin (NG) co-administration can modify the effect of this compound on cognitive functions and inhibit any possible oxidative stress in the brain tissue of rats. Adult male Wistar rats were divided into six groups. Group I: control, Group II: BPA-treated rats (50 mg/kg/day), Group III, IV, V: BPA+NG (40, 80, 160 mg/kg/day), Group VI: NG (160 mg/kg/day) alone. Cognitive functions were evaluated using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) in elevated plus-maze. A significant decrease in SDL, prolongation of TL, noticeable oxidative impairment and increase in acetylcholinesterase activity were observed in the BPA-treated in comparison with the control group. Also, the co-administration of NG (160 mg/kg) antagonized the effect of BPA on SDL and TL, attenuated oxidative damage by lowering malondialdehyde and nitrite concentrations and restored superoxide dismutase, catalase, and glutathione S-transferase activities. On the other hand, acetylcholinesterase activity was reduced in the groups co-administred with NG (80 or 160 mg/kg) and BPA in comparison with the BPA alone-treated group. The present study highlighted the therapeutic potential of NG against BPA-induced cognitive impairment and oxidative damage.

Oxidative stress in normal hematopoietic stem cells and leukemia.

Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000-2017) of English-language literature using the terms 'oxidative stress,' 'reactive oxygen species,' 'hematopoietic stem cell,' and 'leukemia.' The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long-term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject.

Chronic exposure to arsenic and high fat diet additively induced cardiotoxicity in male mice.

Diet is one of the important risk factors that could potentially affect arsenic-induced cardiotoxicity. The present study was undertaken to investigate the effect of high fat diet on arsenic-induced cardiotoxicity in mice. Mice were divided into six different groups (n = 12), two control groups received either low fat diet (LFD) or high fat diet (HFD) along with deionized drinking water and four test groups given LFD + 25 ppm arsenic, LFD + 50 ppm arsenic, HFD + 25 ppm arsenic, and HFD + 50 ppm arsenic in drinking water for 5 months. The body weight, heart weight to body weight ratio, cardiac biochemical markers, lipid profile, and histological examination of heart were evaluated. The results demonstrated that arsenic exposure led to a significant decrease in heart glutathione level, catalase enzyme activity, and a significant increase in reactive oxygen species (ROS), malondialdehyde levels, and biochemical enzymes. The administration of HFD resulted in above-mentioned changes as well as an alteration in lipid profile; however, arsenic exposure alone or along with HFD caused a reduction in lipid profile factors, except HDL level. Our results revealed that HFD increased arsenic-induced heart injury in the mice. This effect may be because of reduction in antioxidant activities and/or increase in oxidative stress and ROS in mice heart tissues. These findings could be important for clinical intervention to protect against or prevent arsenic-induced cardiotoxicity in humans.