OBJECTIVETo investigate the toxic effects of decabromodiphenyl ethane (DBDPE), used as an alternative to decabromodiphenyl ether in vitro.

METHODSHepG2 cells were cultured in the presence of DBDPE at various concentrations (3.125-100.0 mg/L) for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied.

RESULTSAs evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species (ROS). Furthermore, N-acetyl-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability.

CONCLUSIONDBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important role.

Apoptosis ; drug effects ; Bromobenzenes ; toxicity ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Hep G2 Cells ; Humans ; Reactive Oxygen Species ; Time Factors

Information regarding decabromodiphenyl ethane (DBDPE) effects on hepatotoxicity and metabolism is limited. In the present study, Wistar rats were given oral DBDPE at different doses. DBDPE induced oxidative stress, elevated blood glucose levels, increased CYP2B2 mRNA, CYP2B1/2 protein, 7-pentoxyresorufin O-depentylase (PROD) activity, and induced CYP3A2 mRNA, CYP3A2 protein, and luciferin benzylether debenzylase (LBD) activity. UDPGT activity increased with its increasing exposure levels, suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway. The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates, including thyroid hormones, which may, in turn, alter glucose metabolism.
Animals ; Bromobenzenes ; toxicity ; Chemical and Drug Induced Liver Injury ; enzymology ; etiology ; Female ; Flame Retardants ; toxicity ; Liver ; drug effects ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Toxicity Tests

Decabromodiphenylethane (DBDPE) has been widely used as an alternative flame retardant due to the restriction or phase-out of traditional polybrominated diphenyl ethers (PBDEs), and is of increasing concern regarding its ubiquity, persistence, and potential adverse effects. In the present study, the toxicological effects of DBDPE were evaluated using zebrafish as an in vivo model. Upon being exposed to DBDPE-polluted sediments for a short term, it was found that the mortality and malformation of zebrafish (including edema, bent notochord, and bent tail) were not affected even at the highest concentration tested (1000.0 µg/kg dry sediment). Regarding behavioral responses, it was found that zebrafish larvae of 48 hours post fertilization (hpf) in all groups escaped successfully with a touch to the dorsal fin. However, when exposed to the highest DBDPE concentration, the larvae of 120 hpf exhibited significantly smaller distances as compared to the control. Moreover, the results of the acetylcholinesterase (AChE) activity, the expression levels of two important nerve-related genes, and the cell apoptosis all indicated that DBDPE posed low neurotoxicity in embryo-larval zebrafish. The results in this study shed some light on the potential risks of DBDPE in the real environment and highlight the application of the sediment exposure route in the future.
Abnormalities, Drug-Induced ; etiology ; Animals ; Apoptosis ; drug effects ; Behavior, Animal ; drug effects ; Bromobenzenes ; toxicity ; Geologic Sediments ; analysis ; Larva ; drug effects ; Neurotoxicity Syndromes ; etiology ; Water Pollutants, Chemical ; toxicity ; Zebrafish ; embryology

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*toxicity ; Benzophenones/administration & dosage/toxicity ; Benzopyrans/administration & dosage/toxicity ; Bromobenzenes/administration & dosage/toxicity ; Cell Movement/drug effects ; Cells, Cultured ; Diclofenac/administration & dosage/toxicity ; Epithelial Cells/drug effects/metabolism/ultrastructure ; Epithelium, Corneal/cytology/*drug effects/metabolism ; Fluorometholone/administration & dosage/toxicity ; Humans ; L-Lactate Dehydrogenase/metabolism ; Microscopy, Electron, Transmission ; Ophthalmic Solutions ; Propionates/administration & dosage/toxicity

PURPOSE: To compare the additive effects of two types of non-steroidal anti-inflammatory drugs (NSAIDs), bromfenac 0.1% or ketorolac 0.45%, relative to topical steroid alone in cataract surgery. MATERIALS AND METHODS: A total 91 subjects scheduled to undergo cataract operation were randomized into three groups: Group 1, pre/postoperative bromfenac 0.1%; Group 2, pre/postoperative preservative-free ketorolac 0.45%; and Group 3, postoperative steroid only, as a control. Outcome measures included intraoperative change in pupil size, postoperative anterior chamber inflammation control, change in macular thickness and volume, and ocular surface status after operation. RESULTS: Both NSAID groups had smaller intraoperative pupil diameter changes compared to the control group (p<0.05). There was significantly less ocular inflammation 1 week and 1 month postoperatively in both NSAID groups than the control group. The changes in central foveal subfield thickness measured before the operation and at postoperative 1 month were 4.30+/-4.25, 4.87+/-6.03, and 12.47+/-12.24 microm in groups 1 to 3, respectively. In the control group, macular thickness and volume increased more in patients with diabetes mellitus (DM), compared to those without DM. In contrast, in both NSAID groups, NSAIDs significantly reduced macular changes in subgroups of patients with or without DM. Although three ocular surface parameters were worse in group 1 than in group 2, these differences were not significant. CONCLUSION: Adding preoperative and postoperative bromfenac 0.1% or ketorolac 0.45% to topical steroid can reduce intraoperative miosis, postoperative inflammation, and macular changes more effectively than postoperative steroid alone.
Aged ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/pharmacology ; Benzophenones/*administration & dosage/pharmacology ; Bromobenzenes/*administration & dosage/pharmacology ; *Cataract ; *Cataract Extraction ; Female ; Humans ; Inflammation/prevention & control ; Ketorolac/*administration & dosage/pharmacology ; Lens Implantation, Intraocular ; Macular Edema/*prevention & control ; Male ; Middle Aged ; Miosis/*prevention & control ; Phacoemulsification ; Postoperative Complications/drug therapy ; Postoperative Period ; Premedication ; Treatment Outcome

OBJECTIVEThe purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats.

METHODSAnimals were divided into five groups of six rats and treated as follows: Group I was a normal control and received no treatment, Group II received only bromobenzene (10 mmol/kg), Groups III and IV received bromobenzene and Triphala (250 and 500 mg/kg, respectively), Group V received Triphala alone (500 mg/kg), and Group VI received bromobenzene and silymarin (100 mg/kg). Antioxidant status and serum kidney functional markers were analyzed.

RESULTSBromobenzene treatment resulted in significant (P< 0.05) decreases in the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase as well as total reduced glutathione. There was a significant (P< 0.05) increase in lipid peroxidation in kidney tissue homogenates. There were significant (P< 0.05) reductions in the levels of serum total protein and albumin as well as significant (P< 0.05) increases in serum creatinine, urea and uric acid. The oral administration of two different doses (250 and 500 mg/kg) of Triphala in bromobenzene-treated rats normalized the tested parameters. The histopathological examinations of kidney sections of the experimental rats support the biochemical observations.

CONCLUSIONTriphala treatment alleviated the nephrotoxic effects of bromobenzene by increasing the activities of antioxidant enzymes and reducing the levels of lipid peroxidation and kidney functional markers.

Acute Kidney Injury ; chemically induced ; diagnosis ; metabolism ; prevention & control ; Animals ; Antioxidants ; pharmacology ; Bromobenzenes ; pharmacology ; Disease Models, Animal ; Female ; Kidney ; metabolism ; pathology ; Kidney Function Tests ; Medicine, Ayurvedic ; Phyllanthus emblica ; Plant Preparations ; chemistry ; pharmacology ; Plant Structures ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Silymarin ; pharmacology ; Terminalia ; Treatment Outcome