Journal of Toxicology
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Acceptance rate15%
Submission to final decision117 days
Acceptance to publication16 days
CiteScore5.800
Journal Citation Indicator0.670
Impact Factor2.9

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Journal of Toxicology has recently been accepted into Food Science & Technology Abstracts

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Journal of Toxicology publishes papers in all areas of toxicological sciences, including the structure, function, and mechanism of agents toxic to humans and/or animals, as well as toxicological medicine, safety evaluation, and environmental health.

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Chief Editor, Professor You-Cheng Hseu, is based at China Medical University. His research focuses on the biology of free radicals, bioactivity in traditional Chinese medicines, and antioxidants and cosmeceutics.

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Research Article

Acute Oral Toxicological Profile of Croton membranaceus Mull. Arg. Aqueous Stem Extract, a Herbal Treatment for Benign Prostate Hyperplasia, in Male Sprague–Dawley Rats

Croton membranaceus Mull. Arg. is a traditional medicinal plant frequently employed in Ghana for the treatment of benign prostatic hyperplasia and prostate cancer. The objective of this study was to determine the acute oral toxicity of the aqueous stem extract of Croton membranaceus (CMASE) in male Sprague–Dawley (S-D) rats. The acute toxicity of CMASE was evaluated using S-D rats randomly divided into four groups of five animals each. Three groups (low dose, median dose, and high dose) of rats received single oral doses of CMASE (1000, 2500, and 5000 mg/kg body weight, respectively) using an oral gavage. The control group was given distilled water. After 14 days of daily observations, hematological, biochemical, and histopathological analyses were conducted on the rats. From the results obtained, doses of CMASE up to 5000 mg/kg did not cause death or induce any clinical indications of toxicity during the study period. Also, the mean body weight and the hematological indices assessed were not significantly affected by the various doses of CMASE compared to the control group. However, serum uric acid and creatinine levels decreased significantly () 14 days after the extract administration. Serum liver function enzyme levels, including alkaline phosphatase (ALP), alanine aminotransferases (ALT), and aspartate aminotransferases (AST), and serum proteins (total proteins and albumin) exhibited significant () non dose-dependent changes (increases and decreases) in treated groups compared to the controls. Other biochemical indices, however, did not differ significantly between the treated groups and the controls. The gross pathological and histological analysis of the heart, liver, and kidney tissues did not reveal any significant changes in histoarchitecture. The oral LD50 of CMASE in rats was greater than 5000 mg/kg, indicating that the extract was relatively safe. It must, however, be used with care as a substitute for the roots.

Research Article

Bisphenol-A Abrogates Proliferation and Differentiation of C2C12 Mouse Myoblasts via Downregulation of Phospho-P65 NF-κB Signaling Pathway

Previous studies showed that bisphenol-A (BPA), a monomer of polycarbonate plastic, is leached out and contaminated in foods and beverages. This study aimed to investigate the effects of BPA on the myogenesis of adult muscle stem cells. C2C12 myoblasts were treated with BPA in both proliferation and differentiation conditions. Cytotoxicity, cell proliferation and differentiation, antioxidant activity, apoptosis, myogenic regulatory factors (MRFs) gene expression, and mechanism of BPA on myogenesis were examined. C2C12 myoblasts exposed to 25–50 µM BPA showed abnormal morphology, expressing numerous and long cytoplasmic extensions. Cell proliferation was inhibited and was accumulated in subG1 and S phases of the cell cycle, subsequently leading to apoptosis confirmed by nuclear condensation and the expression of apoptosis markers, cleaved caspase-9 and caspase-3. In addition, the activity of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase was significantly decreased. Meanwhile, BPA suppressed myoblast differentiation by decreasing the number and size of multinucleated myotubes via the modulation of MRF gene expression. Moreover, BPA significantly inhibited the phosphorylation of P65 NF-κB in both proliferation and differentiation conditions. Altogether, the results revealed the adverse effects of BPA on myogenesis leading to abnormal growth and development via the inhibition of phospho-P65 NF-κB.

Research Article

NETosis Secondary to the Use of Levamisole-Adulterated Cocaine: A Likely Underlying Mechanism of Vasculopathy

Background. Since 2010, several cases of a new vasculopathy induced by the use of levamisole-adulterated cocaine (LAC) have been reported. This vasculopathy is characterized by retiform purpura, earlobe necrosis, multisystem compromise, and multiple autoantibodies. Given its similarity to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, LAC-associated vasculopathy is postulated to be mediated by pathophysiologic processes resulting from neutrophil cell death by NETosis, a phenomenon previously described in ANCA vasculitis. This study tries to establish the presence of NETosis induced by cocaine, levamisole, or both. Methodology. Neutrophils were isolated from the peripheral blood of healthy controls by Ficoll-Hystopaque density gradient centrifugation followed by dextran sedimentation. Cell viability and purity were evaluated by flow cytometry after staining with PI/DiOC6 and labeling with fluorescent anti-CD45/anti-CD3 monoclonal antibodies (mAbs), respectively. Neutrophils were exposed to levamisole, cocaine, a cocaine-levamisole mixture, and sera pools from healthy controls and patients with LAC-associated vasculopathy. NETosis was then assessed by flow cytometry after staining cells with Sytox Green, Hoechst-33342, and fluorescent antineutrophil elastase (NE) and antimyeloperoxidase (MPO) mAbs. In addition, NETosis was morphologically confirmed by fluorescence microscopy. Proinflammatory cytokine levels in culture supernatants and reactive oxygen species (ROS) synthesis were determined by flow cytometry. The involvement of calcium and muscarinic receptors in cell death induction was evaluated in parallel experiments carried out in the presence of 1,2-bis (o-aminophenoxy) ethane-N, N, N′, N′-tetraacetic acid (BAPTA) and hyoscine butylbromide (HBB), their respective inhibitors. Results. Cocaine, levamisole, and a cocaine-levamisole mixture induced neutrophil cell death. DNA/MPO extrusion and cell morphology patterns were consistent with NETosis. Neither proinflammatory cytokines nor ROS behaved as proNETotic factors. Preliminary results suggested that muscarinic receptors and calcium-dependent signals were involved in LAC-induced NETosis. Conclusions. Cocaine, levamisole, and a cocaine-levamisole mixture can induce NETosis through mechanisms involving muscarinic receptors and calcium-dependent pathways.

Research Article

Effect of Honey and Aqueous Garlic Extracts against Short-Term Exposure of Cigarette Tobacco Smoking in Mice: Histopathological and Biochemical Investigations

It is well known that cigarette smoking adversely affects human health and induces oxidative stress in most vital organs. This study aims to assess the biochemical, histological, and ultrastructural values of honey and garlic extracts in ameliorating the effects of short-term exposure to cigarette smoke in mice. Forty-eight mice were randomly divided into six equal groups: group I was exposed to fresh air only, group II was exposed to cigarette smoke, group III was given 0.2 ml of honey extract, group IV was exposed to cigarette smoke and was given 0.2 ml of honey extract, group V was given 0.2 ml of garlic extract, and group VI was exposed to cigarette smoke and was given 0.2 ml of aqueous garlic extract. These exposures were repeated daily for 21 consecutive days among the treated groups. By the end of the third week, the animals were euthanized by physical cervical dislocation. Blood was taken for biochemical study, and the selected organs of the liver, kidney, and jejunum were processed for histological and ultrastructural studies. The biochemical results showed that short-term exposure of experimental mice to cigarette smoking did not alter the liver function tests except for decreasing the albumin level. Moreover, cigarette smoking elevates the concentration of carbonyl protein content and cystatin C. Histologically, the use of honey and garlic showed good protection to the liver, kidney, and jejunum, which was proved by transmission electron microscopy, in addition to lowering the oxidative stress biomarkers. In conclusion, using honey and/or garlic helps protect the liver, kidney, and jejunum against the hazardous effects of cigarette smoke.

Research Article

Protective and Ameliorative Effects of Hydroethanolic Extract of Piper nigrum (L.) Stem against Antiretroviral Therapy-Induced Hepatotoxicity and Dyslipidemia in Wistar Rats

Antiretroviral therapy (ART) has revolutionized the lives of people living with HIV/AIDS by overall improving their quality of life and increasing life expectancy. However, ART-associated hepatotoxicity and metabolic disorders in HIV/AIDS patients are growing concerns to clinicians, especially due to the long-term use of the drugs. This study reported on the phytochemical and pharmacological profile of hydroethanolic extracts of Piper nigrum stem (PNS) and evaluated its protective effect against tenofovir/lamivudine/efavirenz (TLE)-induced hepatotoxicity and dyslipidemia in Wistar rats. Cytotoxic, antioxidant, and anti-inflammatory assays were performed on PNS. Thirty-six rats divided into 6 groups of 6 animals/group were administered: distilled water, 17 mg/kg TLE, 17 mg/kg TLE and 100 mg/kg silymarin, 17 mg/kg TLE, and Piper extract (200 mg/kg, 400 mg/kg, or 800 mg/kg) orally for 28 days. The body weight of animals was recorded every 7 days. On Day 29, the rats were sacrificed, and blood samples were collected for hematological and biochemical tests. Portions of the liver and kidneys were collected for histological evaluation, while liver homogenates were prepared from the rest to measure antioxidant enzymes. PNS possessed in vitro cytotoxic, antioxidant, and anti-inflammatory activities. A significant decrease in the body weight of rats treated with PNS was observed. A significant high platelet count was observed in the PNS800 mg/kg group. A considerable decrease in alkaline phosphatase and triglycerides was observed in the silymarin and PNS group compared to the TLE-only group. The findings also show a significant increase in catalase and glutathione in the TLE-only group compared to the normal group, while SOD decreased. Histological observations revealed normal hepatic and renal tissues in the silymarin, and PNS-treated groups compared to the normal control, while leucocyte infiltration was observed in the TLE-only group. These results suggest that PNS extract possessed antioxidant activity that alleviated TLE-induced toxicity. Further studies are necessary to understand the pharmacokinetic interactions between ART and PNS.

Research Article

Acute Toxicity and Antioxidant and Antibacterial Activities of Kyllinga polyphylla Willd. ex Kunth, Cyperaceae Family

Kyllinga polyphylla Willd. ex Kunth. (KP) is a wild herb commonly distributed in the Mekong Delta, Vietnam. This study was carried out to evaluate the antibacterial and antioxidant activities and acute toxicity of KP before conducting studies at the in vivo level. All parts of KP had the free radical scavenging capacity of DPPH, in which the root methanol extract had the best antioxidant capacity (EC50 = 9.54 ± 0.37 μg/mL). Most of the extracts had a wide range of antibacterial spectra. The methanol and ethanol extracts (200 mg/mL) have ability to resist eight common bacterial strains (including Staphylococcus aureus, Listeria innocua, Bacillus subtilis, Bacillus cereus, Escherichia coli, Salmonella sp., Pseudomonas aeruginosa, and Enterococcus faecalis), which is equivalent to the antibacterial activity of amoxicillin and tetracycline at a concentration of 1 mg/mL. KP extracts did not cause death at a dose of 5000 mg/kg body weight and did not significantly change the biochemical, hematological, as well as histological structures of internal organs in toxicity-tested mice in comparison with the control. The research results showed that KP should be more interested in research that supports disease treatment, synthetic extraction of antibiotics, or other in vivo studies.

Journal of Toxicology
 Journal metrics
See full report
Acceptance rate15%
Submission to final decision117 days
Acceptance to publication16 days
CiteScore5.800
Journal Citation Indicator0.670
Impact Factor2.9
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