Metabolomic-Based Comparison of Daphnia magna and Japanese Medaka Responses After Exposure to Acetaminophen, Diclofenac, and Ibuprofen.

Pharmaceuticals are found in aquatic environments due to their widespread use and environmental persistence. To date, a range of impairments to aquatic organisms has been reported with exposure to pharmaceuticals; however, further comparisons of their impacts across different species on the molecular level are needed. In the present study, the crustacean Daphnia magna and the freshwater fish Japanese medaka, common model organisms in aquatic toxicity, were exposed for 48 h to the common analgesics acetaminophen (ACT), diclofenac (DCF), and ibuprofen (IBU) at sublethal concentrations. A targeted metabolomic-based approach, using liquid chromatography-tandem mass spectrometry to quantify polar metabolites from individual daphnids and fish was used. Multivariate analyses and metabolite changes identified differences in the metabolite profile for D. magna and medaka, with more metabolic perturbations for D. magna. Pathway analyses uncovered disruptions to pathways associated with protein synthesis and amino acid metabolism with D. magna exposure to all three analgesics. In contrast, medaka exposure resulted in disrupted pathways with DCF only and not ACT and IBU. Overall, the observed perturbations in the biochemistry of both organisms were different and consistent with assessments using other endpoints reporting that D. magna is more sensitive to pollutants than medaka in short-term studies. Our findings demonstrate that molecular-level responses to analgesic exposure can reflect observations of other endpoints, such as immobilization and mortality. Thus, environmental metabolomics can be a valuable tool for selecting sentinel species for the biomonitoring of freshwater ecosystems while also uncovering mechanistic information. Environ Toxicol Chem 2024;00:1-13. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Semirational Design Strategy To Enhance the Thermostability and Catalytic Activity of Cytochrome P450 105D7 for the Degradation of the Pharmaceutically Active Compounds: Diclofenac.

Pharmaceutically active compounds are an important category of emerging pollutants, and their biological transformation processes in the environment are crucial for understanding and evaluating the migration, transformation, and environmental fate of emerging pollutants. The cytochrome P450 105 enzyme family has been proven to play an important role in the degradation of exogenous environmental pollutants. However, its thermostability and catalytic activity still need to be improved to better adapt to complex environmental conditions. This work elucidates the key mechanisms and important residues of the degradation reaction through multiple computational strategies, establishes a mutation library, and obtains 21 single-point mutation designs. Experimental verification showed that 16 single mutants had enhanced thermostability, with the R89F and L197Y mutants showing the highest increases in thermostability at 135 and 119% relative to the wild-type enzyme, respectively. Additionally, as a result of the higher specific activity of D390Q, it was selected for combination mutagenesis, ultimately resulting in three combination mutants (R89F/L197Y, R89F/D390Q, and R89F/L197Y/D390Q) with enhanced thermostability and catalytic activity. This study provides a modification approach for constructing efficient enzyme variants through semirational design and can contribute to the development of control technologies for emerging pollutants.

Antagonistic effects of a COX1/2 inhibitor drug in human HepG2 cells exposed to an environmental carcinogen.

Understanding interactions between legacy and emerging environmental contaminants has important implications for risk assessment, especially when mutagens and carcinogens are involved, whose critical effects are chronic and therefore difficult to predict. The current work aimed to investigate potential interactions between benzo[a]pyrene (B[a]P), a carcinogenic polycyclic aromatic hydrocarbon and legacy pollutant, and diclofenac (DFC), a non-steroidal anti-inflammatory drug and pollutant of emerging concern, and how DFC affects B[a]P toxicity. Exposure to binary mixtures of these chemicals resulted in substantially reduced cytotoxicity in human HepG2 cells compared to single-chemical exposures. Significant antagonistic effects were observed in response to high concentrations of B[a]P in combination with DFC at IC50 and ⅕ IC50. While additive effects were found for levels of intracellular reactive oxygen species, antagonistic mixture effects were observed for genotoxicity. B[a]P induced DNA strand breaks, γH2AX activation, and micronuclei formation at ½ IC50 concentrations or lower, whereas DFC induced only low levels of DNA strand breaks. Their mixture caused significantly lower levels of genotoxicity by all three endpoints compared to those expected based on concentration additivity. In addition, antagonistic mixture effects on CYP1 enzyme activity suggested that the observed reduced genotoxicity of B[a]P was due to its reduced metabolic activation as a result of enzymatic inhibition by DFC. Overall, the findings further support the growing concern that co-exposure to environmental toxicants and their non-additive interactions may be a confounding factor that should not be neglected in environmental and human health risk assessment.

Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates - Harnessing the potential in the construction of materials for skin regeneration processes.

This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling healthy and chronic wound skin. These oligomers were used to make P(3HO) blends, forming patches for drug delivery. Their preparation used the solvent casting/porogen leaching (SCPL) method. The patches' properties like porosity, roughness, and wettability were thoroughly analysed. Antimicrobial assays showed that Dic-oligo(3HAs) exhibited antimicrobial activity against reference (S. aureus, S. epidermis, S. faecalis) and clinical (Staphylococcus spp.) strains. Human keratinocytes (HaCaT) cell line tests, as per ISO 10993-5, showed no toxicity. A clear link between material roughness and HaCaT cell adhesion was found. Deep cell infiltration was verified using DAPI and phalloidin staining, observed under confocal microscopy. SEM also confirmed HaCaT cell growth on these scaffolds. The strong adhesion and proliferation of HaCaT cells on these materials indicate their potential as wound dressing layers. Additionally, the successful diclofenac release tests point to their applicability in treating both normal and chronic wounds.

Renoprotective effect of diacetylrhein on diclofenac-induced acute kidney injury in rats via modulating Nrf2/NF-κB/NLRP3/GSDMD signaling pathways.

Diclofenac (DF)-induced acute kidney injury (AKI) is characterized by glomerular dysfunction and acute tubular necrosis. Due to limited treatment approaches, effective and safe drug therapy to protect against such AKI is still needed. Diacetylrhein (DAR), an anthraquinone derivative, has different antioxidant and anti-inflammatory properties. Therefore, the aim of the current study was to investigate the renoprotective effect of DAR on DF-induced AKI while elucidating the potential underlying mechanism. Our results showed that DAR (50 and 100 mg/kg) markedly abrogated DF-induced kidney dysfunction decreasing SCr, BUN, serum NGAL, and serum KIM1 levels. Moreover, DAR treatment remarkably maintained renal redox balance and reduced the levels of pro-inflammatory biomarkers in the kidney. Mechanistically, DAR boosted Nrf2/HO-1 antioxidant and anti-inflammatory response in the kidney while suppressing renal TLR4/NF-κB and NLRP3/caspase-1 inflammatory signaling pathways. In addition, DAR markedly inhibited renal pyroptosis via targeting of GSDMD activation. Collectively, this study confirmed that the interplay between Nrf2/HO-1 and TLR4/NF-κB/NLRP3/Caspase-1 signaling pathways and pyroptotic cell death mediates DF-induced AKI and reported that DAR has a dose-dependent renoprotective effect on DF-induced AKI in rats. This effect is due to powerful antioxidant, anti-inflammatory, and anti-pyroptotic activities that could provide a promising treatment approach to protect against DF-induced AKI.

Optimized design of quaternary amino-functionalized chitosan fibers for ultra-high diclofenac adsorption from wastewater.

The extraction of non-steroidal anti-inflammatory drugs (NSAIDs) from water bodies is imperative due to the potential harm to humans and the ecosystem caused by NSAID-contaminated water. Quaternary amino-functionalized epichlorohydrin cross-linked chitosan fibers (QECFs), an economical and eco-friendly adsorbent, were successfully prepared using a simple and gentle method for efficient diclofenac (DCF) adsorption. Additionally, the optimized factors for the preparation of QECFs included epichlorohydrin concentration, pH, temperature, and (3-chloro-2-hydroxypropyl) trimethylammonium chloride (CHTAC) concentration. QECFs demonstrated excellent adsorption performance for DCF across a broad pH range of 7-12. The calculated maximum adsorption capacity and the amount of adsorbed DCF per adsorption site were determined to be 987.5 ± 20.1 mg/g and 1.2 ± 0.2, respectively, according to the D-R and Hill isotherm models, at pH 7 within 180 min. This performance surpassed that of previously reported adsorbents. The regeneration of QECFs could be achieved using a 0.5 mol/L NaOH solution within 90 min, with QECFs retaining their original fiber form and experiencing only a 9.18% reduction in adsorption capacity after 5 cycles. The Fourier transform infrared spectrometer and X-ray photoelectron spectroscopy were used to study the characterization of QECFs, the preparation mechanism of QECFs, and the adsorption mechanism of DCF by QECFs. Quaternary ammonium groups (R4N+) were well developed in QECFs through the reaction between amino/hydroxyl groups on chitosan and CHTAC, and approximately 0.98 CHTAC molecule with 0.98 R4N+ group were immobilized on each chitosan monomer. Additionally, these R4N+ on QECFs played a crucial role in the removal of DCF.

Supramolecular Hydrogel Dexamethasone-Diclofenac for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) severely affects patients' quality of life and is commonly treated with glucocorticosteroids injections, like dexamethasone, which may have side effects. This study aimed to create a novel low dose of twin-drug hydrogel containing dexamethasone and diclofenac and explore its potential as a drug delivery system for an enhanced anti-inflammatory effect. Its characterization involved rheology, transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Furthermore, the hydrogel demonstrated thixotropic properties. The hydrogel exhibited no cytotoxicity against RAW 264.7 macrophages. Furthermore, the hydrogel demonstrated a significant anti-inflammatory efficacy by effectively downregulating the levels of NO, TNF-α, and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The co-delivery approach, when intra-articularly injected in adjuvant-induced arthritis (AIA) rats, significantly alleviated chronic inflammation leading to reduced synovitis, delayed bone erosion onset, and the downregulation of inflammatory cytokines. The biocompatibility and adverse effect evaluation indicated good biological safety. Furthermore, the hydrogel demonstrated efficacy in reducing NF-κB nuclear translocation in LPS-induced RAW 264.7 macrophages and inhibited p-NF-kB, COX-2, and iNOS expression both in RAW 264.7 macrophages and the joints of AIA rats. In conclusion, the findings indicate that the hydrogel possesses potent anti-inflammatory activity, which effectively addresses the limitations associated with free forms. It presents a promising therapeutic strategy for the management of RA.

Design and engineering of logic genetic-enzymatic gates based on the activity of the human CYP2C9 enzyme in permeabilized Saccharomyces cerevisiae cells.

Gene circuits allow cells to carry out complex functions such as the precise regulation of biological metabolic processes. In this study, we combined, in the yeast S. cerevisiae, genetic regulatory elements with the enzymatic reactions of the human CYP2C9 and its redox partner CPR on luciferin substrates and diclofenac. S. cerevisiae cells were permeabilized and used as enzyme bags in order to host these metabolic reactions. We engineered three different (genetic)-enzymatic basic Boolean gates (YES, NOT, and N-IMPLY). In the YES and N-IMPLY gates, human CYP2C9 was expressed under the galactose-inducible GAL1 promoter. The carbon monoxide releasing molecule CORM-401 was used as an input in the NOT and N-IMPLY gates to impair CYP2C9 activity through inhibition of the Fe+2- heme prosthetic group in the active site of the human enzyme. Our study provides a new approach in designing synthetic bio-circuits and optimizing experimental conditions to favor the heterologous expression of human drug metabolic enzymes over their endogenous counterparts. This new approach will help study precise metabolic attributes of human P450s.

Synthesis of recyclable and light-weight graphene oxide/chitosan/genipin sponges for the adsorption of diclofenac, triclosan, and microplastics.

Emerging micropollutants, such as pharmaceuticals and microplastics (MPs), have become a pressing water environmental concern. The aim of this study is to synthesize chitosan sponges using graphene oxide (GO) and genipin (GP) for the removal of pharmaceuticals (diclofenac (DCF) and triclosan (TCS)) and MPs, verify their adsorption mechanisms, evaluate the effects of temperature, pH, and salinity on their adsorption capacities, and determine their reusability. The GO5/CS/GP sponge exhibited a macroporous nature (porosity = 95%, density = 32.6 mg/cm3). GO and cross-linker GP enhanced the adsorption of DCF, TCS, and polystyrene (PS) MPs onto the CS sponges. The adsorption of DCF, TCS, and PS MPs involved multiple steps: surface diffusion and pore diffusion of the sponge. The adsorption isotherms demonstrated that Langmuir model was the most fitted well model to explain adsorption of TCS (qm = 7.08 mg/g) and PS MPs (qm = 7.42 mg/g) on GO5/CS/GP sponge, while Freundlich model suited for DCF adsorption (qm = 48.58 mg/g). DCF adsorption was thermodynamically spontaneous and endothermic; however, the adsorption of TCS and PS MPs was exothermic (283-313 K). The optimal pH was 5.5-7 due to the surface charge of the GO5/CS/GP sponge (pHzpc = 5.76) and ionization of DCF, TCS, and PS MPs. As the salinity increased, DCF removal efficiency drastically decreased due to the weakening of electrostatic interactions; however, TCS removal efficiency remained stable because TCS adsorption was mainly caused by hydrophobic and π-π interactions rather than electrostatic interaction. The removal of PS MPs was enhanced by the electrostatic screening effects of high Na+ ions. PS nanoplastics (average size = 26 nm) were removed by the GO5/CS/GP sponge at a rate of 73.0%, which was better than that of PS MPs (41.5%). In addition, the GO5/CS/GP sponge could be recycled over five adsorption-desorption cycles.

Exploring monocarboxylate transporter inhibition for cancer treatment.

Cells are separated from the environment by a lipid bilayer membrane that is relatively impermeable to solutes. The transport of ions and small molecules across this membrane is an essential process in cell biology and metabolism. Monocarboxylate transporters (MCTs) belong to a vast family of solute carriers (SLCs) that facilitate the transport of certain hydrophylic small compounds through the bilipid cell membrane. The existence of 446 genes that code for SLCs is the best evidence of their importance. In-depth research on MCTs is quite recent and probably promoted by their role in cancer development and progression. Importantly, it has recently been realized that these transporters represent an interesting target for cancer treatment. The search for clinically useful monocarboxylate inhibitors is an even more recent field. There is limited pre-clinical and clinical experience with new inhibitors and their precise mechanism of action is still under investigation. What is common to all of them is the inhibition of lactate transport. This review discusses the structure and function of MCTs, their participation in cancer, and old and newly developed inhibitors. Some suggestions on how to improve their anticancer effects are also discussed.

NSAID (nonsteroidal anti-inflammatory drugs) Induced Stevens Johnson Syndrome in a 50-year-old woman: A case study.

Stevens-Johnson Syndrome (SJS) is a severe and rare adverse drug reaction associated with significant morbidity and mortality. Although SJS is commonly triggered by multiple drugs, non-steroidal anti-inflammatory drugs (NSAIDs), including diclofenac, have been frequently implicated. A middle-aged woman, who is 50 years old, has a prior medical record of high blood pressure, type 2 diabetes, and has recently suffered from a pulmonary embolism. She was later admitted to the intensive care unit (ICU), where she was ultimately diagnosed with Steven Johnson syndrome. Careful drug selection, close monitoring of patients with predisposing factors, and prompt identification of adverse events are crucial to prevent severe drug reactions.

Fasting potentiates diclofenac-induced liver injury via inductions of oxidative/endoplasmic reticulum stresses and apoptosis, and inhibition of autophagy by depleting hepatic glutathione in mice.

Diclofenac, a widely used non-steroidal anti-inflammatory drug, can cause liver damage via its metabolic activation by hepatic CYP450s and UGT2B7. Fasting can affect drug-induced liver injury by modulating the hepatic metabolism, but its influence on diclofenac hepatotoxicity is unknown. Thus, we investigated diclofenac-induced liver damage after fasting in mice, and the cellular events were examined. Male ICR mice fasted for 16 h showed the elevation of CYP3A11, but the decreases of UGT2B7, glutathione (GSH), and GSH S-transferase-µ/-π levels in the livers. Diclofenac (200 mg/kg) injection into the mice after 16-h fasting caused more significant liver damage compared to that in the diclofenac-treated fed mice, as shown by the higher serum ALT and AST activities. Diclofenac-promoted hepatic oxidative stress (oxidized proteins, 4-hydroxynonenal, and malondialdehyde), endoplasmic reticulum (ER) stress (BiP, ATF6, and CHOP), and apoptosis (cleaved caspase-3 and cleaved PARP) were enhanced by fasting. Autophagic degradation was inhibited in the diclofenac-treated fasting mice compared to that of the corresponding fed mice. The results suggest that fasting can make the liver more susceptible to diclofenac toxicity by lowering GSH-mediated detoxification; increased oxidative/ER stresses and apoptosis and suppressed autophagic degradation may be the cellular mechanisms of the aggravated diclofenac hepatotoxicity under fasting conditions.

Inhibitory effect of diacerein on diclofenac-induced acute nephrotoxicity in rats via modulating SIRT1/HIF-1α/NF-κB and SIRT1/p53 regulatory axes.

The aim of this study is to explore the potential of repurposing the antiarthritic drug diacerein (DCN) against diclofenac (DCF)-induced acute nephrotoxicity in rats. Rats were divided into four groups: Group I (CTRL) served as the negative control; Group II (DCF) served as the positive control and was injected with DCF (50 mg/kg/day) for three consecutive days (fourth-sixth) while being deprived of water starting on day 5; Group III (DCF + DCN50) and Group IV (DCF + DCN100) were orally administered DCN (50 and 100 mg/kg/day, respectively) for six days and injected with DCF, while being deprived of water as described above. Changes in kidney function biomarkers were assessed. Levels of MDA and GSH along with NO content in kidney tissues were measured as indicators of oxidative stress status. Histopathological changes of the renal cortex and medulla were evaluated. Changes in renal NF-κB and SIRT-1 levels were immunohistochemically addressed. Western blotting was used to estimate the relative expressions of HIF-1α, p53, and active caspase-3. Our results showed that DCN inhibited kidney dysfunction and suppressed oxidative stress, which were reflected in improved kidney architecture, including less tubular degeneration and necrosis in the cortex and medulla. Interestingly, DCN reduced renal HIF-1α, p53, and active caspase-3 expression and NF-κB activation while increasing renal SIRT1 expression. In conclusion, for the first time, DCN counteracts acute kidney injury induced by DCF in rats by its anti-oxidative, anti-inflammatory, antinecrotic, and anti-apoptotic effects in a dose-dependent manner, which are mainly via targeting SIRT1/HIF-1α/NF-κB and SIRT1/p53 regulatory axes.

Topical Immunotherapy for Actinic Keratosis and Field Cancerization.

This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.

An Analytical Target Profile for the Development of an In Vitro Release Test Method and Apparatus Selection in the Case of Semisolid Topical Formulations.

This study focuses on how to define an Analytical Target Profile (ATP) which is intended for use in practice and on facilitating the selection of in vitro release test (IVRT) technology for diclofenac sodium topical hydrogel and cream. The implementation involves incorporating the new draft guidelines of the International Council for Harmonisation (ICH Q14) and USP (United States Pharmacopeia) Chapter 1220. Four IVRT apparatuses were compared (USP Apparatus II with immersion cell, USP Apparatus IV with semisolid adapter, static vertical diffusion cell, and a new, in-house-developed flow-through diffusion cell) with the help of the ATP. Performance characteristics such as accuracy, precision, cumulative amount released at the end of the IVRT experiment, and robustness were investigated. We found that the best apparatus for developing IVRT quality control (QC) tests in both cases was USP II with an immersion cell. All four different IVRT apparatuses were compared with each other and with the data found in the literature.

Development and Evaluation of Two-Phase Gel Formulations for Enhanced Delivery of Active Ingredients: Sodium Diclofenac and Camphor.

The formulation of biphasic gels as potential semi-solid carriers for hydrophilic and lipophilic active substances is promising for the development of pharmaceutical preparations. The aim of this study was to design a stable bigel composition and to determine the influence of the organogel/hydrogel ratio on the gel's physical-chemical and structural-mechanical properties. The investigated compositions of organogel/hydrogel remained stable at ratios ranging from 5/95 to 40/60. After texture and microstructure analysis, bigels with 20/80 and 25/75 ratios were selected as carriers for the active ingredients, sodium diclofenac and camphor, for use as topical preparations for the treatment of muscle-joint inflammation and pain. Although other researchers have published data on the preparation and evaluation of bigels, there are no scientific results on the development of a two-phase gel with our proposed combination of APIs. Sodium diclofenac release was found to be higher when combined with camphor, which revealed the advantages of the biphasic formulation. The pseudoplastic behavior, thixotropy, and thermal stability of flow of the studied bigel samples was investigated by rheological analysis. Ongoing stability studies confirmed the minimal 6-month period.

DIFUCOSIN: DIclofenac sodium salt loaded FUCOidan-SericIN nanoparticles for the management of chronic inflammatory diseases.

The current investigation emphasizes the use of fucoidan and sericin as dual-role biomaterials for obtaining novel nanohybrid systems for the delivery of diclofenac sodium (DS) and the potential treatment of chronic inflammatory diseases. The innovative formulations containing 4 mg/ml of fucoidan and 3 mg/ml of sericin showed an average diameter of about 200 nm, a low polydispersity index (0.17) and a negative surface charge. The hybrid nanosystems demonstrated high stability at various pHs and temperatures, as well as in both saline and glucose solutions. The Rose Bengal assay evidenced that fucoidan is the primary modulator of relative surface hydrophobicity with a two-fold increase of this parameter when compared to sericin nanoparticles. The interaction between the drug and the nanohybrids was confirmed through FT-IR analysis. Moreover, the release profile of DS from the colloidal systems showed a prolonged and constant drug leakage over time both at pH 5 and 7. The DS-loaded nanohybrids (DIFUCOSIN) induced a significant decrease of IL-6 and IL-1ß with respect to the active compound in human chondrocytes evidencing a synergistic action of the individual components of nanosystems and the drug and demonstrating the potential application of the proposed nanomedicine for the treatment of inflammation.

Removal of diclofenac sodium from aqueous solution using different ionic liquids functionalized tragacanth gum hydrogel prepared by radiation technique.

Diclofenac sodium (DCF) was reported as an important emerging environmental pollutant and its removal from wastewater is very urgent. In this study, different alkyl substituted ionic liquids (1-alkyl -3-vinyl- imidazolium bromide [CnVIm]Br, n = 4, 6, 8, 10, 12) functionalized tragacanth gum (TG-CnBr) are prepared by radiation induced grafting and crosslinking polymerization. The adsorption behaviors of ionic liquids functionalized tragacanth gum for diclofenac sodium from aqueous solutions are examined. The adsorption capacity of TG-CnBr for diclofenac sodium increases with the increasing of alkyl chain length of the imidazolium cation and the hydrophobicity of the hydrogels. The maximum adsorption capacity by TG-C12Br for diclofenac sodium at 30, 40 and 50 °C were 327.87, 310.56 and 283.29 mg/g, respectively. The adsorption of TG-C12Br towards diclofenac sodium was little decreased with NaCl increasing. The removal efficiency was still remained 94.55 % within 5 adsorption-desorption cycles by 1 M HCl. Also, the adsorption mechanism including electrostatic attraction, hydrophobic interaction, hydrogen bonding, and π - π interaction was proposed.

Investigating the teratogenic potential of diclofenac sodium on chick embryos: A warning for pregnant women.

Teratogenic and embryotoxic effect of diclofenac sodium (DS) on different developmental stages of the chick-embryos was investigated by examining different parameters such as its mortality rate, hatching, morphological measurements, weighing its internal organs and calculation of different indices. Experiment was divided into four trials with different dose (0.1 mL, 0.2 mL, 0.3 mL in groups A, B, and C, respectively and group D received 0.3 mL saline solution (0.9% NaCl) and group E remained un-injected) administration and observation. Results of first and second trial showed statistically (p<0.01) significant difference in bodyweight, body-length, forelimb and hindlimb length between experimental and control groups. In third trial, diclofenac sodium administration showed a statistically (p<0.01) significant difference in the bodyweight, body-length, forelimb, hindlimb length, liver weight, egg weight (EE ratio) and kidney somatic index (KSI). The beak-size, heart weight, kidney weight, cardiac somatic index (CSI) and hepato somatic index (HSI) were not significant (p>0.05) when compared with the control groups. In trial 4, forelimb, hindlimb length, heart weight, CSI and HSI were statistically (p<0.01) significant. Body-length and liver weight were significant (p<0.05). While bodyweight, beak size, kidney weight and KSI were non-significant (p>0.05). The mortality rate was increased with increase dose of DS and also affected the hatching. DS effect on chick embryos can be applied to humans because the early development of mammals and birds are closely related. So, it was concluded that DS should be used with caution during pregnancy especially during first trimester of pregnancy.

Anaphylactic Shock After Intramuscular Diclofenac Sodium: A Case Report.

Diclofenac sodium is a commonly used nonsteroidal anti-inflammatory drug. It is widely used for acute and chronic pain management. Side effects, such as fixed drug eruption, asthmatic attack, and vasospastic angina, are commonly seen after the use of diclofenac sodium. However, anaphylaxis and anaphylactic shock secondary to injection of diclofenac sodium are rare. Our main aim in reporting this adverse event is to alert healthcare professionals to this potentially life-threatening adverse effect of diclofenac sodium and prompt use of adrenaline for treatment.