Begell House Inc.
Journal of Environmental Pathology, Toxicology and Oncology
JEP(T)
0731-8898
39
3
2020
Safety Concerns of Organic Ultraviolet Filters: Special Focus on Endocrine-Disrupting Properties
201-212
10.1615/JEnvironPatholToxicolOncol.2020033188
Didem
Oral
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey
Anil
Yirun
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Sıhhiye 06100, Ankara, Turkey; Çukurova University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Adana, Turkey
Pinar
Erkekoglu
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey
organic UV filter
sunscreen
UV radiation
endocrine disruption
toxicity
Acute and chronic effects of ultraviolet radiation (UVR) on human health have long been a concern. It is well known that acute UVR causes epidermal hyperplasia, erythema, delayed tanning, pigment darkening, and free-radical formation. Apart from acute effects of UVR, its chronic effects involve immunosuppression, photoaging, exacerbation, photodermatoses, and photocarcinogenesis. To protect skin from harmful effects of UVR, UV filters were developed. But these may cause harmful effects in humans and on the environment; adverse effects of these chemicals have been evaluated for > 20 yr. Studies show that UV filters may lead to endocrine disruption, hepatotoxicity, mutagenicity, and systemic toxicity. Literature on environmental effects of UV filters suggests that they are bioaccumulative, pseudopersistent, and possibly toxic to aquatic ecosystems. The objective of this review is to summarize toxic effects and safety concerns of organic UV filters on human beings and the environment. We focus on UV filters' organic endocrine-disrupting effects by reviewing both in vivo and in vitro studies.
Effect of Betulin on Inflammatory Biomarkers and Oxidative Status of Ova-Induced Murine Asthma
213-224
10.1615/JEnvironPatholToxicolOncol.2020031970
Lei
Wang
Tianjin Medical University General Hospital, Tianjin City, 300052, China; Tianjin Chest Hospital, Tianjin City, 300222, China
Diansheng
Zhong
Tianjin Medical University General Hospital, Tianjin City, 300052, China
KEY WORDS: asthma
TNF-a
IFN-gamma
betulin
airway hyperreactivity
IgE
MDA
ovalbumin
Asthma is a chronic, serious allergic inflammatory disease in the airway. The inflammation in the airway is induced by the allergic T-helper 2 cells (Th2 cells), which leads to unfettered production of inflammatory cytokines. The accretion of inflammatory cells in the airway also speeds up the secretion of reactive oxygen species (ROS) and suppresses antioxidative processes. Hence, the present work aimed to study the antiasthmatic efficacy of betulin and its effect in suppressing the inflammatory markers of ovalbumin (OVA) challenged asthmatic mice. The observed results revealed that the levels of inflammatory cells including neutrophils, eosinophils, lymphocytes, and macrophages were effectively decreased by betulin treatment; furthermore, the inflammatory markers IL-4, IL-5, IL-13, and TNF-α levels were notably suppressed by betulin administration in OVA-challenged asthmatic mice. Similarly, the oral administration of betulin showed a reduction in IgE level and elevation in the IFN-γ level in bronchoalveolar lavage fluid (BALF). The elevated levels of antioxidant enzymes like catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were observed in betulin treated mice. Furthermore, reduced levels of reactive oxygen species like NO2, NO3, and MDA were noted in the betulin treated group. Consistently, airway hyperreactivity (AHR) was depleted in the betulin administered group compared with the OVA-challenged asthmatic group. Betulin treatment was revealed to have noteworthy antiasthmatic effects mediated by the suppression of production of inflammatory cells and the expression of other inflammatory markers. Furthermore, the elevation in the level of antioxidant markers helped to disclose the original regulatory mode of betulin on asthma treatment.
Effects of Boldine on Antioxidants and Allied Inflammatory Markers in Mouse Models of Asthma
225-234
10.1615/JEnvironPatholToxicolOncol.2020034039
Wei
Li
Department of Pediatrics, Shanghai General Hospital, Shanghai, China
Vishnu Priya
Veeraraghavan
Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600 077, India
Weining
Ma
Department of Pediatrics, Shanghai General Hospital, Shanghai, China
antioxidants
asthma
airway inflammation
boldine
interleukins
oxidative stress
Asthma is marked by chronic irritation in the airway lumen of the lungs due to the accretion of inflammatory cells that influence the regular inhalation process. An extended buildup of inflammation leads to oxidative pressure and the repression of antioxidant functions. In the current study, a potential compound, boldine, was tested for the containment of provocative markers along the path of antiasthmatic activity in an ovalbumin (OVA)-induced asthmatic mice model. As an effect, the boldine (10 and 20 mg/kg) treatment suppressed inflammatory cells such as eosinophil, macrophage, neutrophil, lymphocyte, and other inflammatory markers in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. Likewise, immunoglobulin E (IgE) levels were drastically condensed in the serum of boldine-treated animals. Levels of enzymatic and nonenzymatic antioxidants, such as superoxide dismutase (SOD) and glutathione (GSH), were upregulated in the boldine treatment group compared to the asthmatic control group, which displays the antioxidant effects of boldine on asthmatic animals. Interestingly, the reactive oxygen species (ROS) and malonaldehyde (MDA) levels were repressed in the BALF of boldine-treated mice groups. Therefore, the effects of boldine are significant for the management of asthma, reducing the accrual of inflammatory cells, along with other inflammatory markers, while improving antioxidant markers and containing ROS. Hence, boldine may be an option for clinical trials of chronic asthma management.
Protective Effect of D-Carvone against Dextran Sulfate Sodium Induced Ulcerative Colitis in Balb/c Mice and LPS Induced RAW Cells via the Inhibition of COX-2 and TNF-α
235-245
10.1615/JEnvironPatholToxicolOncol.2020031860
Xiaoyan
Zhu
Department of Gastroenterology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250013, P.R. China
Guo
Wang
Department of Third Anorectal, The People’s Hospital of Huaiyin, Jinan, Shandong Province, 250021, P.R. China
Shuang
Wu
Cangzhou Medical College, Yingbindadao West Higher Education District, Yunhe District, Cangzhou, Hebei Province, 061001, P.R. China
Chengzhen
Li
Department of Two Gastrointestinal Tract, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, No. 105, Jiefang Road, Lixia District, Jinan, Shandong Province, 250013, P.R. China
colitis
D-carvone
lipopolysaccharides
RAW-264.7 cells
iNOS
TNF-a
sulfasalazine
COX-2
TBARS and oxidative stress
Ulcerative colitis (UC) is an intractable ailment, in which may chronic inflammations/ulcerations may develop in the mucosal lining of the colon with multiple recurrences. Various drugs such as steroids, immunosuppressants, and antibiotics are extensively used to treat UC. The patients suffer from adverse effects of these advanced drugs. So, they need a harmless therapeutic agent from natural sources. The therapeutic D-carvone has an anti-inflammatory action against the investigational colon cancer models. Therefore, we analyzed the effect of D-carvone on dextran sulfate sodium (DSS) provoked colitis model in mice as follows: Group I: noncolitis healthy control mice; Group II: ulcerative colitis mice models; Group III: D-carvone (40 mg/kg) + ulcerative colitis models; Group IV: sulfasalazine (50 mg/kg) + ulcerative colitis models. On the 8th day, the experimental study was terminated and serum samples and colon tissues were processed for further analysis. The effect of D-carvone at different concentration was studied on the LPS challenged RAW 264.7 cell lines. The D-carvone (40 mg/kg) treatment maintained the colon length and decreased disease activity index (DAI) score in UC animals. The increased antioxidant enzymes status and decreased oxidative stress and pro-inflammatory markers were noted in the D-carvone (40 mg/ kg) + UC mice. Histopathological study of colon tissue of D-carvone (40 mg/kg) treated UC mice displayed less mucosal damage and improved crypt integrity and goblet cells compared with DSS only provoked mice. The im-munohistochemical expression of iNOS and COX-2 was drastically diminished in the D-carvone treated UC mice. D-carvone (40 mg/kg) treatment appreciably diminished the LPS provoked NO production and pro-inflammatory modulators in the RAW 264.7 macrophage cell lines. These findings proved that D-carvone has a potential therapeutic effect to prevent LPS induced inflammation in in vitro cells and chemically induced ulcerative colitis in vivo models.
Malvidin Abrogates Oxidative Stress and Inflammatory Mediators to Inhibit Solid and Ascitic Tumor Development in Mice
247-260
10.1615/JEnvironPatholToxicolOncol.2020034430
KM
Sakthivel
Assistant Professor (SG),
Krishnamoorthy
Kokilavani
Department of Biochemistry, PSG College of Arts and Science, Civil Aerodrome Post, Coimbatore-641014, Tamil Nadu, India
Chinnadurai
Kathirvelan
Department of Animal Nutrition, Veterinary College and Research Institute, Tamil Nadu Veterinary and Animal Sciences University (TANUVAS), Namakkal-637002, Tamil Nadu, India
Durairaj
Brindha
Department of Biochemistry, PSG College of Arts and Science, Civil Aerodrome Post, Coimbatore-641014, Tamil Nadu, India
Dalton's lymphoma ascites
malvidin
reactive oxygen species
tumor
cytokines
CTX
The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.
Cross Talk between Mitochondria and Other Targets in Alzheimer's Disease
261-279
10.1615/JEnvironPatholToxicolOncol.2020034249
Rehana
Khatoon
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
Monika
Pahuja
Division of Basic Medical Sciences, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, V. RamalingaswamyBhawan, P.O. Box No. 4911, New Delhi – 110029, India
Suhel
Parvez
Associate Professor and Head
mitochondria
endoplasmic reticulum
Golgi apparatus
reactive oxygen species
neurodegenerative diseases
apoptosis
Among the neurodegenerative diseases, Alzheimer's disease (AD) is a predominant public health issue, affecting 16 million people around the world. It is clinically manifested by the presence of amyloid plaques (Aβ) and neurofibrillary tangles (NFT) within the brain. Due to intraneuronal processing, Aβ interacts with cellular targets such as mitochondria, ER, and Golgi apparatus and hampers their normal functions. Alteration in the mitochondrial function, closely related to the production of reactive oxygen species (ROS), Ca+2 overload, and apoptosis in the brain, is one of the key pathological events studied in AD pathogenesis. It is also an important pivot for the intracellular interaction with ER and Golgi through signal transduction and membrane contact to regulate cell survival and death mechanism. Alteration in mitochondrial function is intimately connected with abnormal ER or Golgi function. Stimuli that enhance perturbation in the normal ER or Golgi organelles function can involve mitochondria mediated apoptotic cell death. In this review, we address the importance of the mitochondria and their cross talk with ER and Golgi in AD pathogenesis and animal models with a therapeutic strategy to improve the mitochondrial functions.
Cystathionine β Synthase/Hydrogen Sulfide Signaling in Multiple Myeloma Regulates Cell Proliferation and Apoptosis
281-290
10.1615/JEnvironPatholToxicolOncol.2020034851
Minmin
Zhang
Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
Juan
Li
Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
Beihui
Huang
Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
Lifen
Kuang
Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
Fei
Xiao
Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
Dong
Zheng
Department of Hematology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China
bone marrow
mononuclear cells
cystathionine gamma lyase
cell cycle
CBS/H2S system
Objective-To investigate cystathionine β synthase (CBS)/hydrogen sulfide (H2S) signaling in multiple myeloma (MM) patients and to identify its effect on the proliferation of U266 cells.
Methods-Bone marrow samples of 19 MM patients and 23 healthy donors were collected. qRT-PCR was performed to measure the mRNA expression levels of H2S synthases, cystathionine β synthase, and cystathionine γ lyase. ELISA assays quantified the amount of H2S produced by the two enzymes CBS and CSE. CCK-8 experiment was used to investigate the influence of the CBS inhibitor amino oxyacetic acid and the CSE inhibitor propargylglycine on the proliferation of U266 cells. Flow cytometry and western blotting were performed to determine the effects of AOAA, PAG, and NaHS on cell cycle distribution as well as Caspase-3 and Bcl-2 expression.
Results-Patients with MM had higher level of CBS compared with healthy donors. AOAA significantly inhibited cell proliferation in both a time and concentration dependent characteristic, whereas PAG does not. After 24 hours of treatment, AOAA significantly elevated the G0/G1 phase proportion of cells, and reduced the cell distribution in both S and G2/M phases, while NaHS accelerated cell cycle progression by reducing the relative number of cells in G0/G1 phase and increasing the proportion of cells in the G2/M phase. Moreover, AOAA abolished the impact of NaHS on cell cycle progression of U266 cells. AOAA treatment also led to a significant decrease in Bcl-2 expression and dramatic increase in Caspase-3 expression, though NaHS reversed these effects.
Conclusion-CBS/H2S system might have a certain effect on the proliferation and apoptosis of MM cells.