Begell House Inc.
Journal of Environmental Pathology, Toxicology and Oncology
JEP(T)
0731-8898
33
2
2014
Protective Effect of Acacia ferruginea against Ulcerative Colitis via Modulating Inflammatory Mediators, Cytokine Profile and NF-κB Signal Transduction Pathways
83-98
10.1615/JEnvironPatholToxicolOncol.2014008425
Kunnathur Murugesan
Sakthivel
Karunya University, Department of Biotechnology, Karunya Nagar, Coimbatore−641114, Tamil Nadu, India; Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India
Chandrasekaran
Guruvayoorappan
Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram - 695011, Kerala, India
Acacia ferruginea
acetic acid
ulcerative colitis
pro-inflammatory cytokines
inducible nitric oxide synthase (iNOS)
cyclo-oxygenase-2 (COX-2)
In the present study, we evaluated the protective effect of A. ferruginea extract against ulcerative colitis (UC). Male Wistar rats received A. ferruginea extract (10 mg/kg body weight) or sulfasalazine (100 mg/kg body weight) for 5 consecutive days before inducing UC via intrarectal acetic acid (3%) administration. Colonic mucosal injury was assessed by macroscopic scoring, vascular permeability testing, and histopathological examination. The mucosal contents of glutathione, lipid peroxidation, superoxide dismutase, and nitric oxide were evaluated as parameters for the redox state. Inflammatory response was determined by measuring inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) expression. Myeloperoxidase (MPO), lactate dehydrogenase assay (LDH), tumor necrosis factor (TNF-α), and interleukins (IL-1β and IL-6) were measured using ELISA. Transcription factor profiling of nuclear factor (NF)-κB subunits (p65/p50) was also conducted using ELISA. All of the relevant parameters were altered in rats with UC, and these parameters improved in animals that received A. ferruginea extract. Colonic mucosal injury parallels antioxidant and anti-inflammatory evaluations, and A. ferruginea extract was considered comparable to the standard treatment drug sulfasalazine. Histopathological studies confirmed these findings. A. ferruginea extract inhibited the activation and translocation of transcription factors, that is, NF-κB subunits (p65/p50). The results of our investigation clearly indicate that treatment with A. ferruginea extract exerted a marked protective effect against experimental UC via modulation of oxidant/anti-oxidant balance and inhibition of inflammatory mediators.
In Vivo Toxicity of the Culturable Marine Cyanobacterium Geitlerinema pseudacutissimum CNP 1019 Extract on Male Swiss Albino Mice (Mus musculus)
99-109
10.1615/JEnvironPatholToxicolOncol.2014010409
Veerabadhran
Maruthanayagam
Department of Marine Biotechnology, National Facility for Marine Cyanobacteria, Bharathidasan University, Tiruchirappalli, India
Manivel
Nagarajan
Department of Marine Biotechnology, National Facility for Marine Cyanobacteria, Bharathidasan University, Tiruchirappalli, India
Sundararaman
Muthuraman
Bharathidasan University
cyanobacteria
cyanotoxins
organ damage
serum enzymes
subchronic toxicity
In this study, we investigated the in vivo toxicity of Geitlerinema pseudacutissimum CNP 1019 organic extract in a murine host. A single intraperitoneal injection of 1 g extract kg−1 body weight (BW) did not exhibit mortality, whereas 3 g extract kg−1 BW (approximate lethal dose) resulted in mortality within 5 days. To perform subchronic exposure toxicity analyses (i.e., daily exposure for a total of 14 days), a maximum concentration of ≤1 g extract kg−1 BW was used. Subchronic toxicity studies in the treated mice, showed fluctuations of feed intake, loss of body weight, increase in specific activity of serum lactate dehydrogenase, alanine aminotransferase and decrease in whole serum protein concentration. LDH isoenzyme expression was found, and levels of the various isoforms were decreased as a result of the treatment. Histopathology studies in liver, kidney, and spleen isolated from the treated mice showed the presence of necrotic debris, hemorrhage, and micronuclei revealing the toxicity of the extract. The dose-dependent alterations in biochemical parameters in conjunction with the histological lesions noted in the animals treated with the prepared extract illustrate the likely potential toxicity to mammals from any encounters with the studied cyanobacterium.
Relationship between Genotoxic Effects of Breast Cancer Treatments and Patient Basal DNA Integrity
111-121
10.1615/JEnvironPatholToxicolOncol.2014010592
Maria Paula
Ceballos
Institute of Experimental Physiology (IFISE), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531 (2000) Rosario, Argentina
Juan Capitaine
Funes
Mastology service of the Centenario Hospital, Urquiza 3101 (2000) Rosario, Argentina
Estefania
Massa
Area of Clinical Biochemistry, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531 (2000) Rosario, Argentina
German
Cipulli
Mastology service of the Centenario Hospital, Urquiza 3101 (2000) Rosario, Argentina
Alfonso Benitez
Gil
Mastology service of the Provincial Hospital, Alem 1450 (2000) Rosario, Argentina
Carlos Capitaine
Funes
Mastology service of the Centenario Hospital, Urquiza 3101 (2000) Rosario, Argentina
Roberto
Tozzini
Mastology service of the Centenario Hospital, Urquiza 3101 (2000) Rosario, Argentina
Sergio
Ghersevich
Area of Clinical Biochemistry, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531 (2000) Rosario, Argentina
comet assay
genotoxic damage
peripheral blood lymphocytes
prognostic factors
Radiotherapy and chemotherapy cause genotoxic side effects that are highly variable among patients. In this study, we evaluated DNA integrity using the comet assay in peripheral blood lymphocytes from breast cancer patients before ("pre-treatment patients"; n = 47) and after ("post-treatment patients"; n = 24) radiotherapy and/or chemotherapy treatment and from healthy donors (n = 15). Comet evaluation was made by visual (types 0−4) and digital (percentage of DNA remaining in the comet head = % head DNA) analysis. The association between the level of DNA damage and cancer prognostic factors was assessed. The treatments caused a significant increase in DNA damage registered by both visual (p < 0.001) and digital (p < 0.001) analyses. No significant associations between the level of DNA damage in pre-treatment patients and cancer prognostic factors were found. A significant correlation between the comet results from each patient before and after treatment (r = 0.64, p = 0.001) was observed. The % head DNA in post-treatment samples from patients with a high level of DNA damage before treatment (30.3 ± 3.1%, p < 0.01) was lower than in post-treatment samples from patients with a low-to-medium level of DNA damage before therapy (49.2 ± 4.4%). These results support the usefulness of the comet assay as a sensitive technique to evaluate basal DNA status and DNA damage caused by cancer treatments. The comet assay could contribute to treatment decisions, especially by taking into account the patient's basal DNA damage before therapy.
Effects of Maternally Exposed Food Coloring Additives on Laryngeal Histology in Rats
123-130
10.1615/JEnvironPatholToxicolOncol.2014008723
Kayhan
Basak
Dr.Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey
Duygu Kumbul
Doguc
Suleyman Demirel University, Medical School, Medical Biochemistry Department, Isparta, Turkey
Firdevs
Aylak
Suleyman Demirel University, Medical School, Medical Biochemistry Department, Isparta, Turkey
Nimet
Karadayi
Dr. Lutfi Kirdar Kartal Education and Research Hospital, Department of Pathology, Istanbul, Turkey
Fatih
Gultekin
Suleyman Demirel University, Medical School, Medical Biochemistry Department, Isparta, Turkey
coloring food additives
genotoxicity
larynx histology
maternal exposure
Experimental reports showed carcinogenic effects of artificial food colors and additives (AFCAs) on many organs, including the head and neck region. We aimed to investigate the effect of AFCAs on laryngeal histomorphology and immunohistochemical expression in maternally exposed rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Histopathological and immunohistochemical findings were evaluated in their offspring. Significant decreasing in goblet cell count and cilia loss were observed with AFCAs in maternally exposed rats (p < 0.05). Immunohistochemically, the Ki67 index was significantly increased and villin expression was significantly reduced in laryngeal epithelium in the study group (p < 0.05), whereas expression of cyclooxygenase type 2, Muc-2, Muc-5AC, p53, and epidermal growth factor receptors did not differ between the groups. This study demonstrated that maternal exposure of AFCAs plays a role in the mucosal defense system and possibly in carcinogenesis.
Antioxidant and Hepatoprotective Effects of Crataegus songarica Methanol Extract
131-143
10.1615/JEnvironPatholToxicolOncol.2014010606
Showkat Ahmad
Ganie
Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
Tanveer Ali
Dar
Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
Bilal
Zargar
Department of Pharmacy, University of Kashmir, Srinagar, India
Rabia
Hamid
Department of Biochemistry, University of Kashmir, Srinagar, India
Ovais
Zargar
Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
Parvaiz Ahmad
Dar
Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
Shayaq Ul
Abeer
Department of Biotechnology, University of Kashmir, Srinagar, India
Akbar
Masood
Department of Biochemistry, University of Kashmir, Srinagar, India
Shajrul
Amin
Department of Biochemistry, University of Kashmir, Srinagar, India
Mohammad Afzal
Zargar
Department of Clinical Biochemistry, University of Kashmir, Srinagar, India
hepatoprotective effect
Crataegus songarica extract
liver injury
chronic CCl4 paracetamol
oxidative stress
The protective activity of the methanolic extract of the Crataegus songarica leaves was investigated against CCl4- and paracetamol-induced liver damage. On folklore levels, this plant is popularly used to treat various toxicological diseases. We evaluated both in vitro and ex vivo antioxidant activity of C. songarica. At higher concentration of plant extract (700 µg/ml), 88.106% inhibition on DPPH radical scavenging activity was observed and reducing power of extract was increased in a concentration-dependent manner. We also observed its inhibition on Fe2+/ascorbic acid-induced lipid peroxidation on rat liver microsomes in vitro. In addition, C. songarica extract exhibited antioxidant effects on calf thymus DNA damage induced by Fenton reaction. Hepatotoxicity was induced by challenging the animals with CCl4 (1 ml/kg body weight, i.p.) and paracetamol (500 mg/kg body weight) and the extract was administered at three concentrations (100, 200, and 300 mg/kg body weight). Hepatoprotection was evaluated by determining the activities of liver function marker enzymes and antioxidant status of liver. Administration of CCl4 elevated the levels of liver function enzymes, SGOT, SGPT, and LDH. We also observed a dramatic increase in ALT, AST, bilirubin, and alkaline phosphatase levels in rats administered 500 mg/kg body weight of paracetamol. Decreased antioxidant defense system as glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), and superoxide dismutase (SOD) were observed in rats treated with CCl4 and paracetamol. Pretreatment with the extract decreased the elevated serum GOT, GPT, LDH, bilirubin, and alkaline phosphatase activities and increased the antioxidant enzymes in a dose-dependent manner. Therefore, C. songarica methanol extract may be an effective hepatic protective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.
Antitumor and Wound Healing Properties of Rubus niveus Thunb. Root
145-158
10.1615/JEnvironPatholToxicolOncol.2014010949
Blassan Plackal
George
Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India
Thangaraj
Parimelazhagan
Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India
Thankarajan
Sajeesh
Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India
Shanmugam
Saravanan
Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India
antioxidant
wound healing
antitumor
HPLC
Quercetin
Rubus niveus
The main objective of this study is to highlight the importance of Rubus niveus in the pharmaceutical industry for the development of cost-effective drugs. The study was undertaken to explore the HPLC profile, wound healing, antitumor, and free radical scavenging properties of R. niveus. The root of R. niveus was extracted using organic solvents and subjected to in vitro antioxidant assays. Acetone extract, which showed better in vitro antioxidant properties, was evaluated for in vivo antioxidant, wound healing, and antitumor properties. The polyphenolic acetone extract showed significant in vivo antioxidant, wound healing, and antitumor properties. In the wound healing study, complete epithelialization was noticed during the 13th to 17th days for treated groups. The 250 mg/kg group was found to prolong the life span of mice with Ehrlich ascites carcinoma (70.04%) and reduced the volume of Daltons lymphoma ascites solid tumors (2.07 cm3). The HPLC analysis of acetone extract revealed the presence of Quercetin, a natural flavonoid with the retention time of 20.89 min. The results of the current study suggest the use of R. niveus as a valuable natural antioxidant that has an immense scope as an effective source to cure skin diseases, wounds, and tumors.
Epigenetic Targets of Polyphenols in Cancer
159-165
10.1615/JEnvironPatholToxicolOncol.2014011094
Pinglin
Yang
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University Medical School, Xi'an, Shaanxi, China
Xijing
He
Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University Medical School, Xi'an, Shaanxi, China
Anshoo
Malhotra
Department of Biophysics, PGIMER, Chandigarh India 160012
epigenetics
polyphenols
cancer
curcumin
methylation
Interest in dietary polyphenols has recently increased greatly owing to their antioxidant capacity and their possible beneficial implications in various pathological states, including cancer. Polyphenols are a group of chemicals found in many fruits, vegetables, and plants and have the ability to remove free radicals from the body. In the last 2 decades, the numbers of reports on the potential health benefits of polyphenols have increased. This review provides the available scientific data that justify importance of polyphenols in correlation with epigenetics to fight against carcinogenesis. Epigenetics involves genetic control by mechanisms other than DNA sequence. These epigenetic mechanisms have ability to switch on or off various important genes influencing the process of cancer. Furthermore, due to the reversible nature of these epigenetic mechanisms, they are influenced by a variety of dietary polyphenols. This review focuses on the dietary polyphenols that significantly affect these epigenetic mechanisms to mitigate carcinogenesis.
Reversal of Methylmercury-Induced Oxidative Stress, Lipid Peroxidation, and DNA Damage by the Treatment of N-Acetyl Cysteine: A Protective Approach
167-182
10.1615/JEnvironPatholToxicolOncol.2014010291
Deepmala
Joshi
Reproductive Biology and Toxicology Laboratory, UNESCO Satellite center of Trace Element Research & School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India
Mittal Deepak
Kumar
Reproductive Biology and Toxicology Laboratory, UNESCO Satellite center of Trace Element Research & School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India
Shakya Arvind
Kumar
Indira Gandhi National Open University, Biochemistry Department, School of Sciences, New Delhi, India
Shukla
Sangeeta
Reproductive Biology and Toxicology Laboratory, UNESCO Satellite center of Trace Element Research & School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India
methylmercury
N-acetyl cysteine
lipid peroxidation
dlutathione
DNA damage
This study was designed to evaluate the protective effect of N-acetyl cysteine in reducing methylmercury (MeHg)−induced oxidative stress, lipid peroxidation, DNA damage in liver, kidney, and brain, and their ability to restore altered hepatic, renal, and other biochemical variables. Male Sprague-Dawley rats (150 ± 10 g) were randomly divided into three groups. Group 1 served as the control. Groups 2 and 3 were administered methylmercury (1 mg kg−1 orally, 5 days/week) for 12 weeks, and group 2 served as the experimental control. Group 3 received N-acetyl cysteine (0.6 mg kg−1 intraperitoneally, two days/week) for 12 weeks after methylmercury exposure. Methylmercury exposure caused a significant rise in bilirubin, gamma-glutamyl transpeptidase, protein, triglycerides, cholesterol, urea,
creatinine, uric acid, and blood urea nitrogen, with a concomitant decrease in albumin content, reduced glutathione
level and acetyl cholinesterase activity, antioxidant enzymes such as glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. However, lipid peroxidation level, metallothionein expression, and DNA damage with increment of tail length were observed after methylmercury intoxication. N-acetyl cysteine, a widely available, nontoxic amino acid derivative, is a promising antioxidant with a wide spectrum of biological functions. The ability of N-acetyl cysteine to enhance mercury excretion and its wide availability in clinical use indicate that it may be an ideal therapeutic agent against methylmercury poisoning.