scholarly journals Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1694 ◽  
Author(s):  
Laura E. Ewing ◽  
Charles M. Skinner ◽  
Charles M. Quick ◽  
Stefanie Kennon-McGill ◽  
Mitchell R. McGill ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Stress Responses ◽  
Total Bilirubin ◽  
Metabolizing Enzymes ◽  
Expression Arrays ◽  
Gene Expression Arrays ◽  
B6c3f1 Mice ◽  
Acute Study ◽  
Cannabis Extract ◽  
Oxidative Stress Responses

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 (MED) of the maximum recommended human maintenance dose of CBD in EPIDIOLEX® (20 mg/kg). In the acute study, significant increases in liver-to-body weight (LBW) ratios, plasma ALT, AST, and total bilirubin were observed for the 2460 mg/kg dose. In the sub-acute study, 75% of mice gavaged with 615 mg/kg developed a moribund condition between days three and four. As in the acute phase, 615 mg/kg CBD increased LBW ratios, ALT, AST, and total bilirubin. Hepatotoxicity gene expression arrays revealed that CBD differentially regulated more than 50 genes, many of which were linked to oxidative stress responses, lipid metabolism pathways and drug metabolizing enzymes. In conclusion, CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature. The involvement of numerous pathways associated with lipid and xenobiotic metabolism raises serious concerns about potential drug interactions as well as the safety of CBD.

scholarly journals Acute toxicity of arsenic and oxidative stress responses in the embryonic development of the common South American toadRhinella arenarum

2015 ◽  
Vol 34 (5) ◽  
pp. 1009-1014 ◽  
Author(s):  
Mariana Noelia Mardirosian ◽  
Cecilia Inés Lascano ◽  
Ana Ferrari ◽  
Guillermina Azucena Bongiovanni ◽  
Andrés Venturino
Keyword(s):  
Oxidative Stress ◽  
Acute Toxicity ◽  
Embryonic Development ◽  
Stress Responses ◽  
South American ◽  
The Common ◽  
Oxidative Stress Responses ◽  
And Oxidative Stress

Assessment of oxidative DNA damage, oxidative stress responses and histopathological alterations in gill and liver tissues of Oncorhynchus mykiss treated with linuron

2020 ◽  
pp. 096032712098420
Author(s):  
Ahmet Topal ◽  
Arzu Gergit ◽  
Mustafa Özkaraca
Keyword(s):  
Dna Damage ◽  
Stress Responses ◽  
Oxidative Dna Damage ◽  
Chloride Cells ◽  
Histopathological Changes ◽  
Sod Activity ◽  
Antioxidant Responses ◽  
Secondary Lamellae ◽  
Antioxidant Parameters ◽  
Oxidative Stress Responses

We investigated changes in 8-hydroxy-2-deoxyguanosine (8-OHdG) activity which is a product of oxidative DNA damage, histopathological changes and antioxidant responses in liver and gill tissues of rainbow trout, following a 21-day exposure to three different concentrations of linuron (30 µg/L, 120 µg/L and 240 µg/L). Our results indicated that linuron concentrations caused an increase in LPO levels of liver and gill tissues ( p < 0.05). While linuron induced both increases and decreases in GSH levels and SOD activity, CAT activity was decreased by all concentrations of linuron ( p < 0.05). The immunopositivity of 8-OHdG was detected in the hepatocytes of liver and in the epithelial and chloride cells of the secondary lamellae of the gill tissues. Our results suggested that linuron could cause oxidative DNA damage by causing an increase in 8-OHdG activity in tissues, and it induces histopathological damage and alterations in the antioxidant parameters of the tissues.

Dynamic aqueous transformations of lithium cobalt oxide nanoparticle induce distinct oxidative stress responses of B. subtilis

2021 ◽  
Author(s):  
Metti K. Gari ◽  
Paul Lemke ◽  
Kelly H. Lu ◽  
Elizabeth D. Laudadio ◽  
Austin H. Henke ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cobalt Oxide ◽  
Stress Responses ◽  
Lithium Ion ◽  
Model Organisms ◽  
Lithium Cobalt Oxide ◽  
Oxygen Species ◽  
Oxide Nanoparticle ◽  
Oxidative Stress Responses ◽  
Lithium Cobalt

Lithium cobalt oxide (LiCoO2), an example of nanoscale transition metal oxide and a widely commercialized cathode material in lithium ion batteries, has been shown to induce oxidative stress and generate intracellular reactive oxygen species (ROS) in model organisms.

scholarly journals Epigallocatechin-3-Gallate Protects Pro-Acinar Epithelia Against Salivary Gland Radiation Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 3162
Author(s):  
Erni Sulistiyani ◽  
James M. Brimson ◽  
Ajjima Chansaenroj ◽  
Ladawan Sariya ◽  
Ganokon Urkasemsin ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Ex Vivo ◽  
Biological Effects ◽  
Branching Morphogenesis ◽  
Epithelial Proliferation ◽  
Expression Arrays ◽  
Gene Expression Arrays ◽  
Antioxidant Agents ◽  
Bright Field Microscopy ◽  
Injury Models

Antioxidant agents are promising pharmaceuticals to prevent salivary gland (SG) epithelial injury from radiotherapy and their associated irreversible dry mouth symptoms. Epigallocatechin-3-gallate (EGCG) is a well-known antioxidant that can exert growth or inhibitory biological effects in normal or pathological tissues leading to disease prevention. The effects of EGCG in the various SG epithelial compartments are poorly understood during homeostasis and upon radiation (IR) injury. This study aims to: (1) determine whether EGCG can support epithelial proliferation during homeostasis; and (2) investigate what epithelial cells are protected by EGCG from IR injury. Ex vivo mouse SG were treated with EGCG from 7.5–30 µg/mL for up to 72 h. Next, SG epithelial branching morphogenesis was evaluated by bright-field microscopy, immunofluorescence, and gene expression arrays. To establish IR injury models, linear accelerator (LINAC) technologies were utilized, and radiation doses optimized. EGCG epithelial effects in these injury models were assessed using light, confocal and electron microscopy, the Griess assay, immunohistochemistry, and gene arrays. SG pretreated with EGCG 7.5 µg/mL promoted epithelial proliferation and the development of pro-acinar buds and ducts in regular homeostasis. Furthermore, EGCG increased the populations of epithelial progenitors in buds and ducts and pro-acinar cells, most probably due to its observed antioxidant activity after IR injury, which prevented epithelial apoptosis. Future studies will assess the potential for nanocarriers to increase the oral bioavailability of EGCG.

scholarly journals The Arabidopsis mediator complex subunit 8 regulates oxidative stress responses

2021 ◽  
Author(s):  
Huaming He ◽  
Jordi Denecker ◽  
Katrien Van Der Kelen ◽  
Patrick Willems ◽  
Robin Pottie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Salicylic Acid ◽  
Jasmonic Acid ◽  
Stress Responses ◽  
Negative Regulator ◽  
Mediator Complex ◽  
Defense Gene Expression ◽  
A Genome ◽  
Oxidative Stress Responses

Abstract Signaling events triggered by hydrogen peroxide (H2O2) regulate plant growth and defense by orchestrating a genome-wide transcriptional reprogramming. However, the specific mechanisms that govern H2O2-dependent gene expression are still poorly understood. Here, we identify the Arabidopsis Mediator complex subunit MED8 as a regulator of H2O2 responses. The introduction of the med8 mutation in a constitutive oxidative stress genetic background (catalase-deficient, cat2) was associated with enhanced activation of the salicylic acid pathway and accelerated cell death. Interestingly, med8 seedlings were more tolerant to oxidative stress generated by the herbicide methyl viologen (MV) and exhibited transcriptional hyperactivation of defense signaling, in particular salicylic acid- and jasmonic acid-related pathways. The med8-triggered tolerance to MV was manipulated by the introduction of secondary mutations in salicylic acid and jasmonic acid pathways. In addition, analysis of the Mediator interactome revealed interactions with components involved in mRNA processing and microRNA biogenesis, hence expanding the role of Mediator beyond transcription. Notably, MED8 interacted with the transcriptional regulator NEGATIVE ON TATA-LESS, NOT2, to control the expression of H2O2-inducible genes and stress responses. Our work establishes MED8 as a component regulating oxidative stress responses and demonstrates that it acts as a negative regulator of H2O2-driven activation of defense gene expression.

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