Toxicity Of Ibuprofen Research Articles

Transient vertical diplopia following ibuprofen intake: a case report.

Ibuprofen, a commonly used over-the-counter medication, is widely recognized for its effective pain relief properties but is also associated with various adverse effects, including rare ocular and neurological manifestations. We report a case of a 27-year-old male who experienced transient vertical diplopia following a standard ibuprofen dosage for back pain. Symptoms resolved promptly upon discontinuation of the drug, with normal findings on extensive clinical and laboratory evaluations. The clinical presentation, suggestive of skew deviation, implies central toxicity. This case underscores the potential for diplopia associated with NSAIDs like ibuprofen to be underdiagnosed and offers valuable insights into the central toxicity of ibuprofen. Further research is warranted to elucidate the underlying mechanisms and optimize patient care in similar scenarios.

Effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems with two filling modes: Performance and toxic response mechanism

To investigate the effect of ibuprofen (IBU) on the sulfur-based and calcined pyrite-based autotrophic denitrification (SCPAD) systems, two individual reactors with the layered filling (L-SCPAD) and mixed filling (M-SCPAD) systems were established via sulfur and calcined pyrite. Effluent NO3−-N concentration of the L-SCPAD and M-SCPAD systems was first increased to 6.44, 0.93 mg/L under 0.5 mg/L IBU exposure and gradually decreased to 1.66 mg/L, 0 mg/L under 4.0 mg/L IBU exposure, indicating that NO3−-N removal performance of the M-SCPAD system was better than that of the L-SCPAD system. The variation of extracellular polymeric substances (EPS) characteristics demonstrated that more EPS was secreted in the M-SCPAD system compared to the L-SCPAD system, which contributed to forming a more stable biofilm structure and protecting microorganisms against the toxicity of IBU in the M-SCPAD system. Moreover, the increased electron transfer impedance and decreased cytochrome c implied that IBU inhibited the electron transfer efficiency of the L-SCPAD and M-SCPAD systems. The decreased adenosine triphosphate (ATP) and electron transfer system activity (ETSA) content showed that IBU inhibited metabolic activity, but the M-SCPAD system exhibited higher metabolic activity compared to the L-SCPAD system. In addition, the analysis of the bacterial community indicated a more stable abundance of nitrogen removal function bacteria (Bacillus) in the M-SCPAD system compared to the L-SCPAD system, which was conducive to maintaining a stable denitrification performance. The toxic response mechanism based on the biogeobattery effect was proposed in the SCPAD systems under IBU exposure. This study provided an important reference for the long-term toxic effect of IBU on the SCPAD systems.

Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism

AimIbuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen metabolism in a Chinese population. MethodsFirst, 31 CYP2C19 and 12 CYP3A4 microsomal enzymes were identified using an insect expression system. Then, variants were evaluated using a mature incubation system. Moreover, ibuprofen metabolite content was determined via ultra-performance liquid chromatography-tandem mass spectrometry analysis. Finally, kinetic parameters of CYP2C19 and CYP3A4 genotypes were determined via Michaelis-Menten curve fitting. ResultsMost variants exhibited significantly altered intrinsic clearance compared to the wild type. In the CYP2C19 metabolic pathway, seven variants exhibited no significant alterations in intrinsic clearance (CLint), six variants exhibited significantly high CLint (121–291%), and the remaining 15 variants exhibited substantially reduced CLint (1–71%). In the CYP3A4 metabolic pathway, CYP3A4*30 was not detected in the metabolite content due to the absence of activity, and 10 variants exhibited significantly reduced CLint. ConclusionTo the best of our knowledge, this is the first study to assess the kinetic characteristics of 31 CYP2C19 and 12 CYP3A4 genotypes on ibuprofen metabolism. However, further studies are needed on poor metabolizers as they are more susceptible to drug exposure. Our findings suggest that the kinetic characteristics in combination with artificial intelligence to predict the toxicity of ibuprofen and reduce any adverse drug reactions.

Hydroxyl radical dominated ibuprofen degradation by UV/percarbonate process: Response surface methodology optimization, toxicity, and cost evaluation

Ibuprofen (IBP) is a typical nonsteroidal anti-inflammatory drug with a wide range of applications, large dosages, and environmental durability. Therefore, ultraviolet-activated sodium percarbonate (UV/SPC) technology was developed for IBP degradation. The results showed that IBP could be efficiently removed using UV/SPC. The IBP degradation was enhanced with prolonged UV irradiation time, with the decreasing IBP concentration and the increasing SPC dosage. The UV/SPC degradation of IBP was highly adaptable to pH ranging from 4.05 to 8.03. The degradation rate of IBP reached 100% within 30 min. The optimal experimental conditions for IBP degradation were further optimized using response surface methodology. IBP degradation rate reached 97.3% under the optimal experimental conditions: 5 μM of IBP, 40 μM of SPC, 7.60 pH, and UV irradiation for 20 min. Humic acid, fulvic acid, inorganic anions, and natural water matrix inhibited the IBP degradation to varying degrees. Scavenging experiments of reactive oxygen species indicated that hydroxyl radical played a major role in the UV/SPC degradation of IBP, while carbonate radical played a minor role. Six IBP degradation intermediates were detected, and hydroxylation and decarboxylation were proposed as the primary degradation pathways. An acute toxicity test, based on the inhibition of luminescence in Vibrio fischeri, indicated that the toxicity of IBP during UV/SPC degradation decreased by 11%. An electrical energy per order value of 3.57 kWh m−3 indicated that the UV/SPC process was cost-effective in IBP decomposition. These results provide new insights into the degradation performance and mechanisms of the UV/SPC process, which can potentially be used for practical water treatment in the future.

Assessment of ibuprofen toxicity and removal potential of Chlorella vulgaris

Ibuprofen, a most widely used anti-inflammatory drug, is frequently detectable in surface water, which might negatively affect the ecosystem. The present research investigated acute toxicity of ibuprofen to Chlorella vulgaris, and ibuprofen removal by C. vulgaris was also evaluated via a first order kinetic model. The results showed that ibuprofen in water has certain freshwater ecological risks, and ibuprofen-contaminated water can be effectively treated by C. vulgaris. The growth and the photosynthetic activity of C. vulgaris were decreased with the increase in ibuprofen exposure concentration, while superoxide dismutase and catalase activities were markedly promoted. The dry weight of C. vulgaris exposed to 100 mg/L ibuprofen was determined as 0.238 ± 0.008 g/L, which was 60.82% of the control group (without added ibuprofen in medium). The capacity of C. vulgaris to ibuprofen removal was decreased with the increase in ibuprofen concentration. The removal efficiency reached to 67.25% after 10-day treatment at ibuprofen concentration of 25 mg/L, while that was just 32.77% when the ibuprofen concentration increased to 100 mg/L. The ibuprofen removal by C. vulgaris accorded with the first-order kinetic model, and the removal rate constants of C. vulgaris to different ibuprofen concentrations (25, 50, 75 and 100 mg/L) were determined as 0.115, 0.097, 0.093 and 0.043 d−1, respectively.

The use of Gammarus pulex as a model organism for ecotoxicological assessment of ibuprofen and propranolol at environmental relevant concentrations

ABSTRACT The aim of this study is to assess the toxicity of ibuprofen (IBU) and propranolol (PRO) drugs usingGammarus pulex as a model organism. Firstly, the 96 h LC50 values of IBU and PRO were determined and then three sublethal concentrations of the drugs were exposed to G. pulex . The activities of superoxide dismutase (SOD), catalase (CAT) and acetylcholinesterase (AChE) were evaluated. SOD activity decreased in G. pulex exposed to IBU and PRO compared to control. In all groups exposed to IBU, CAT activity increased at different concentrations at 24 and 96 h. In the groups exposed to different PRO concentrations, CAT activities increased after 24 h compared to the control group (p < 0.05). AChE activities increased in all application groups exposed to IBU for 96 hours (p < 0.05). In conclusion, exposure to IBU and PRO resulted in increased oxidative damage. PRO has been found to cause neurotoxicity.

Antioxidant markers in gills, liver and muscle tissue of the African Sharptooth Catfish (Clarias gariepinus) exposed to subchronic levels of Ibuprofen and Dibutyl phthalate

The increasing influx of various emerging pollutants into the aquatic environment has become topical in recent times. This study was carried out to investigate the sublethal toxicity of ibuprofen (IBP) and dibutyl phthalate (DBP) on antioxidant markers in Clarias gariepinus exposed for 30 days. The results showed that SOD activity was significantly induced in the exposed fishes throughout the study period for both toxicants. CAT activity was induced significantly in the liver throughout the study period. In contrast, in the gill, there was an initial significant increase, followed by a significant inhibition as the study progressed for both toxicants. The GST activity was significantly induced in the liver and the gills of fishes exposed to both toxicants.In contrast, there was a significant increase in the GST activity in the muscle tissue of fish exposed to both toxicants in the first 15 days; afterward, there was a significant decrease in fish exposed to 0.2 mg/L of DBP. The GSH activity was significantly reduced in all sampled organs exposed to both toxicants at the end of the study period, although there was a significant increase in the GSH activity in fishes exposed to both toxicants at 15 days. The LPO in all sampled organs was significantly inhibited at 15 days of exposure to both toxicants. It was then followed by a significant increase at the end of the study period. This study's findings have shown that IBP and DBP at very low concentrations can elicit oxidative stress by altering antioxidant markers, leading to a high incidence of lipid peroxidation, thus, disrupting the normal functioning of the cell membranes.

Chronic levels of ibuprofen induces haematoxic and histopathology damage in the gills, liver, and kidney of the African sharptooth catfish (Clarias gariepinus).

Numerous active pharmaceutical ingredients (APIs) have been detected in various environmental matrices. Thus, their potential to elicit their toxic effect on non-target organisms is a growing concern, especially in the aquatic environment. This study aimed to investigate the potential toxicity of ibuprofen (IBU) at environmentally relevant concentration on the haematology and histology of the gill, liver, and kidney over 30days. The 96-h acute toxicity data showed that IBU was moderately toxic to C. gariepinus with an LC50 value of 3.78mg/L. After 15 and 30days of exposure, there was a significant alteration in haematological indices in the treated fishes when compared to the control group. Throughout the experimental duration, the level of the mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) were consistently lower significantly, in contrast to the control group. IBU induced histopathological deformities in the gills, liver, and kidney of the exposed fishes, with alterations such as showing severe secondary lamella necrosis (SLN), epithelial lifting (EL), mild deformity of the secondary lamella (DSL), mild secondary lamella necrosis (MLN), and mild vascular congestion in the liver and kidney, respectively. This study has demonstrated that IBU at environmentally relevant concentrations can significantly impact the haematology, gills, liver, and kidney of C. gariepinus. This study's results can provide baseline info for regulatory agencies to set safe limits for NSAIDs as a safeguard for the aquatic environment.

Influence of ibuprofen and its biotransformation products on different biological sludge systems and ecosystem

Ibuprofen (IBU) is one of the frequently detected non-steroidal anti-inflammatory drugs (NSAIDs) in wastewater treatment plants (WWTPs) and aquatic environment. However, little is known about the effect of IBU and its biotransformation products (TPs) on different biological sludge systems and aquatic environment. The effects and toxicity of IBU and TPs on three biological sludge systems (i.e., activated sludge (AS), sulfate-reducing bacteria (SRB)-enriched sludge and anaerobic methanogenic (AnM) sludge systems) and aquatic environment were comprehensively evaluated through a long-term operation of three bioreactors and a series of batch experiments. Both of the SRB-enriched sludge and AnM sludge systems were not affected under a long-term exposure to IBU, based on removing organic carbon and sulfur and producing methane. This could be attributed to the high tolerance of functional microbes in the SRB-enriched sludge (e.g., genus Desulfobacter) and AnM sludge systems (e.g., genus Candidatus Methanomethylicus) for IBU. In contrast, IBU had some apparently inhibitory effects on the AS system, such as reduced organic removal efficiency and poor sludge settling. The analysis on microbial community revealed that IBU significantly inhibited the genera involved in organic degradation (e.g., genus Candidatus Competibacter) and also stimulated those genera (e.g., genus Brachymonas) to secret excess extracellular polymeric substances (EPS), which thus caused sludge bulking in the AS system. The toxicity of IBU and its TPs in the effluent of the AS system was also investigated with Vibrio fischeri bioluminescence inhibition tests and quantitative structure activity relationship (QSAR) analysis by ecological structure-activity relationship (ECOSAR) program. The results indicated that the AS system could effectively eliminate the acute toxicity of both IBU and TPs, but a potential chronic toxicity of IBU could still existed, which could be more harmful to aquatic organisms than that of its TPs. These findings provide an insight into the toxic effects of IBU and its TPs on biological sludge systems and ecosystem.

Ibuprofen Increases the Hepatotoxicity of Ethanol through Potentiating Oxidative Stress.

Over 30 million prescriptions of NSAIDs (non-steroidal anti-inflammatory drugs) are issued every year. Considering that these drugs are available without a prescription as over the counter (OTC) drugs, their use will be astronomical. With the increasing use of NSAIDs, their adverse effects are drawing attention. Especially, stomach bleeding, kidney toxicity, liver toxicity, and neurological toxicity are reported as common. Ibuprofen, one of the extensively used NSAIDs along with aspirin, can also induce liver toxicity, but few studies are addressing this point. Here we examined the liver toxicity of ibuprofen and investigated whether co-exposure to ethanol can manifest synergistic effects. We employed 2D and 3D cultured human hepatoma cells, HepG2 to examine the synergistic hepatotoxicity of ibuprofen and alcohol concerning cell viability, morphology, and histology of 3D spheroids. As a result, ibuprofen and alcohol provoked synergistic hepatotoxicity against hepatocytes, and their toxicity increased prominently in 3D culture upon extended exposure. Oxidative stress appeared to be the mechanisms underlying the synergistic toxicity of ibuprofen and alcohol as evidenced by increased production of ROS and expression of the endogenous antioxidant system. Collectively, this study has demonstrated that ibuprofen and EtOH can induce synergistic hepatotoxicity, providing a line of evidence for caution against the use of ibuprofen in combination with alcohol.

Preparation, characterization and improved release profile of ibuprofen-phospholipid association

Ibuprofen is a widely prescribed non-steroidal and anti-inflammatory drug, which is practically insoluble in water and causes gastrointestinal (GI) side effects. Ibuprofen-phosphathidylcholine association (IPA) was prepared by refluxing ibuprofen and phosphathidylcholine in three different molar ratios (1:0.25, 1:0.5 and 1:1) in aim to induce the amorphous nature of ibuprofen and increase its solubility. The characteristics of IPA were evaluated by H1-NMR, FT-IR spectra, X ray diffraction (XRD), differential scanning calorimetry (DSC), drug content, photon correlation spectroscopy, computational molecular simulation, solubility and in vitro dissolution study. Computational molecular simulation, DSC, FT-IR, H1-NMR and XRD patterns confirmed the reaction between carboxyl group of ibuprofen and polar moiety of phosphathidylcholine. IPAs showed an increase in solubility in phosphate buffer medium (pH 7.2) and a decrease in solubility in HCl medium (pH 1.2). The IPA dissolution rate increased in the simulated intestinal medium, whereas the dissolution rate of the IPA decreased in the simulated gastric medium. It is concluded that the phosphatidylcholine association of ibuprofen may be of potential use for improving the ibuprofen solubility and hence its bioavailability. Furthermore, considering decrease of dissolution rate of IPA in acidic medium, it may also reduce GI toxicity of ibuprofen. Moreover, comparing different molar ratios of IPA, there is no significant difference in their characteristics and dissolution profiles.

Treatment of ibuprofen intoxication with charcoal haemoperfusion in two dogs

ABSTRACTCase history: Two dogs presented separately to the Small Animal Hospital, University of Florida (Gainsville, FL, USA) for ingestion of ibuprofen. The first dog ingested 561.8 mg/kg ibuprofen in addition to paracetamol and caffeine and vomited prior to admission. This patient also received fluid therapy for 8 hours prior to charcoal haemoperfusion. The second dog ingested 500 mg/kg of ibuprofen and the owners induced vomiting with hydrogen peroxide prior to presentation. Due to the severity of clinical signs, both patients were treated with charcoal haemoperfusion.Clinical findings: The concentrations of ibuprofen in the blood of the dogs prior to treatment were 478 and 301 mg/L. During the treatment ibuprofen concentrations were reduced by 95.8% and 45.5%, respectively, with no treatment side effects and minimal clinical signs after treatment.Diagnosis: Toxicity due to ingestion of ibuprofen toxicity that was successfully treated with charcoal haemoperfusion.Clinical relevance: In the cases described here minimal benefit was seen after 3 hours of treatment using one haemoperfusion cartridge. This is in contrast to a previously published report in which dogs were treated for 6 hours with two charcoal haemoperfusion cartridges. This suggests that one cartridge may be sufficient. The amount of ibuprofen ingested was not a reliable predictor of the concentration in blood at the initiation of treatment. Charcoal haemoperfusion is an effective means of reducing plasma concentrations of ibuprofen, however, its use may be limited by its cost and availability.

Amphibian embryos as an alternative model to study the pharmaceutical toxicity of cyclophosphamide and ibuprofen

Pharmaceuticals are becoming potentially ubiquitous pollutants because of their extensive use by man. One of the most frequent groups of pharmaceuticals that have been identified as particularly concerning is that of nonsteroidal anti-inflammatory and chemotherapeutic drugs. In Albania, studies to determine the risk of pharmaceuticals in conjunction with their occurrence in water bodies and their adverse effects on living organisms, including humans, are scarce. The purpose of this study was to elucidate the possible toxic effects of ibuprofen (IBU) and cyclophosphamide (CP) on cellular physiology of frog tadpoles. For this purpose, individuals of Pelophylax shqipericus belonging to stage 21 Gosner were exposed to sub-lethal concentration (5 μg/L) of IBU and CP for 48 hours, and erythrocyte abnormalities and micronucleated cell frequency were evaluated as endpoints. Blood smears from tadpoles exposed to CP for 48 hours showed a pronounced decrease in the number of red blood cells and an increase in the percentage of micronucleated erythrocytes through chromatin fragmentation, while abnormalities like cellular and nuclear vacuolization, collapse and rupture of the cell membrane were caused by IBU toxicity. Understanding the biological effects of these drugs on frog tadpoles can help in using these animals as reliable bio-indicator organisms in monitoring aquatic environments health.

Biochemical alterations in plasma total bile acid, creatinine, sodium, potassium, chloride, and bicarbonate in rabbits overdosed with ibuprofen and supplemented with guava leaf (Psidium guajava) extracts

STUDY BACKGROUND: Ibuprofen is an analgesic and a nonsteroidal anti-inflammatory drug while Psidium guajava leaf has antioxidative, antimicrobial, anti-inflammatory, and analgesic activities. AIM AND OBJECTIVE: The aim of the study is to evaluate plasma total bile acids (TBAs), creatinine, and electrolytes in rabbits overdosed with ibuprofen and supplemented with guava leaf (P. guajava) extracts. JUSTIFICATION: There exists a little information on the change in the plasma levels of TBA and electrolytes in ibuprofen toxicity supplemented with guava leaf extract. MATERIALS AND METHODS: Fifteen rabbits (weight – 0.8–1.4 kg; age – 1.5 ± 0.4 years, n = 5/group) were grouped into control (a); rabbits administered 1600 mg/KgBW of ibuprofen (B1) before being fed with 400 mg/KgBW of guava leaf aqueous extract (B2) and rabbits administered 1600 mg/KgBW of ibuprofen administration (C1) before being fed with 400 mg/KgBW of guava leaf methanolic extract (C2). Plasma creatinine, sodium, potassium, chloride, and bicarbonate levels were determined using COBAS C111 chemistry autoanalyzer while TBA was determined by spectrophotometry. RESULTS: The results showed a significant increase in the plasma level of TBA, potassium, and creatinine in the rabbits following the administration of 1600 mg/KgBW of ibuprofen (P CONCLUSION: There was a significant increase in the plasma values of TBA, creatinine, and potassium following the administration of ibuprofen possibly due to ibuprofen toxicity which was significantly reduced upon the administration of 400 mg/KgBW of guava leaf extract.

A Very Rare Case of Ibuprofen—Induced Acute Liver Failure

iDILI due to ibuprofen is quite rare, occurring in approximately 1 per 100,000 patients. The patient will typically have a hypersensitivity reaction as well, such as toxic epidermal necrolysis or Stevens Johnson syndrome. While chronic ibuprofen use may cause transaminitis, it is typically no more than the low 100s. Ibuprofen overdose (greater than 5—10 grams) is typically associated with altered mental status, respiratory depression, coma and lactic acidosis, which may prove fatal. Most cases have not been associated with liver injury. A 29yo F was admitted for altered mental status. She was lethargic and not answering questions. Per her mother, she had taken around 300 tabs of 200mg ibuprofen. Medical history included depression, asthma, alcohol abuse and past drug abuse. She was tachycardic and hypotensive. Initial CBC and BMP were normal. She was intubated and dialyzed for ibuprofen overdose. Mental status returned to normal and she was extubated. She developed transaminitis and elevation of INR, so GI was consulted. Differentials included ischemic liver from her initial hypotension and ibuprofen toxicity. Her transaminitis worsened, but transplant hepatology stated she was not a candidate for emergent transplant. With supportive care, her transaminitis began to downtrend. She still required intermittent dialysis due to acute renal failure. She was discharged to the psych unit for further monitoring, where her transaminitis eventually resolved. In this patient, the initial thought process revolved around ischemic shock liver, while ibuprofen toxicity was a secondary differential. However, once her LFTs did not begin to downtrend as expected, ibuprofen toxicity quickly became the leading differential. While it is exceedingly rare in general, it is even more rare in this case because it was not accompanied by any systemic signs or symptoms. Overall, when it comes to acute liver failure, iDILI ranks second to acetaminophen toxicity (11% compared to 46%). Only about 10% of those with iDILI will progress to acute liver failure, but about 60% of those will require liver transplant. The severity of the liver injury is typically unpredictable and the main therapies are withdrawal of the suspected agent along with supportive care. Of note, corticosteroids have not been shown to play a major role in therapy. N—acetyl cysteine may be administered, but the most important prognostic factors are not only early detection but timely evaluation for liver transplant.3046_A.tif Figure 1: Trend of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and platelets.3046_B.tif Figure 2: Trend of international normalized ratio (INR), total bilirubin, and albumin.

Evaluation of tumor necrosis factor alpha (TNFα), interleukin 4, interleukin 6, aspartate aminotransferase, and alanine aminotransferase in rabbits overdosed with ibuprofen and supplemented with guava leaf (Psidium guajava) extract

Introduction: Guava leaf contains low calorie, vitamins, minerals antioxidants, polyphenolic, and flavonoid compounds which may play important role in prevention of cancers, aging, cell differentiation, apoptosis and may also have immune enhancing properties while ibuprofen is a nonsteroidal anti inflammatory drug commonly used to relief pain. It reduces hormones that cause inflammation and pain in the body.This project work was therefore designed to evaluate the plasma level of pro (tumor necrosis factor alpha (TNFα)) and anti inflammatory (interleukin 4 [IL 4] and 6) cytokines, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in rabbits overdosed with ibuprofen and supplemented with guava leaf extract. Methods: Fifteen rabbits grouped into three experimental groups labeled A–C (with subgroups B1, B2, C1, and C2) with A as control were investigated. An overdose of ibuprofen of 1600 mg/kgBW was administered to Group B and C rabbits to induce toxicity, while 400 ml/kgBW guava leaf extract was used to reduce and treat ibuprofen toxicity. Plasma tumor necrosis factor alpha (TNFα), IL-4 and 6, AST, and ALT were analyzed biochemically by spectrophotometry and enzyme-linked immunosorbent assay. Results: The result obtained showed a significant increase in the plasma value of TNF-α, IL-4, IL-6, ALT, and AST in rabbits induced with 1600 mg/kgBW of ibuprofen per oral fed with normal meal for 7 days (Group B1 and C1) compared with normal rabbits fed with normal meal and water only for 7 days (Group A) (P

Abiotic degradation and environmental toxicity of ibuprofen: Roles of mineral particles and solar radiation

The growing medical and personal needs of human populations have escalated release of pharmaceuticals and personal care products into our natural environment. This work investigates abiotic degradation pathways of a particular PPCP, ibuprofen, in the presence of a major mineral component of soil (kaolinite clay), as well as the health effects of the primary compound and its degradation products. Results from these studies showed that the rate and extent of ibuprofen degradation is greatly influenced by the presence of clay particles and solar radiation. In the absence of solar radiation, the dominant reaction mechanism was observed to be the adsorption of ibuprofen onto clay surface where surface silanol groups play a key role. In contrast, under solar radiation and in the presence of clay particles, ibuprofen breaks down to several fractions. The decay rates were at least 6-fold higher for irradiated samples compared to those of dark conditions. Toxicity of primary ibuprofen and its secondary residues were tested on three microorganisms: Bacillus megaterium, Pseudoaltermonas atlantica; and algae from the Chlorella genus. The results from the biological assays show that primary PPCP is more toxic than the mixture of secondary products. Overall, however, biological assays carried out using only 4-acetylbenzoic acid, the most abundant secondary product, show a higher toxic effect on algae compared to its parent compound.

Activation of intestinal GR-FXR and PPARα-UGT signaling exacerbates ibuprofen-induced enteropathy in mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200mg/kg) in the small intestine of mice, which was not due to the pregnane-X-receptor pathway. Instead, glucocorticoid receptor (GR) mediated the effect of DEX (5mg/kg) on both the acute (200mg/kg) and 7-day repeated-dose (50mg/kg) toxicity of IBU in the small intestine. Combined treatment of DEX (5mg/kg) and IBU (50mg/kg) synergistically repressed the intestinal farnesoid X receptor (FXR)-cystathionine-γ-lyase signaling, which was accompanied with an elevation in the biliary excretion of bile acids, especially the FXR antagonist tauro-β-muricholic acid. DEX (5mg/kg) also activated intestinal peroxisome proliferator-activated receptor α (PPARα)-UDP-glucuronosyltransferase (UGT) pathway, which increased the formation and enterohepatic circulation of IBU-acyl glucuronide. Furthermore, DEX (5mg/kg) and IBU (50mg/kg) altered the intestinal microbial composition, characterized with a marked decrease in Actinobacteria. To conclude, the present study for the first time suggests that glucocorticoids play vital roles in control of IBU enteropathy via intestinal GR-FXR and PPARα-UGT signaling.

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen

Background: Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. Methods: A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. Results: The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Conclusion: Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity.

Toxicological interactions of ibuprofen and triclosan on biological activity of activated sludge

The growing use of pharmaceutical and personal care products increases their concentrations in the wastewater entering treatment plants and their levels into biological reactors. The most extended biological wastewater treatment is the activated sludge process. The toxicity of ibuprofen and triclosan, individually and combined, was studied by tracking the biological activity of the activated sludge measuring oxygen uptake rate and the inhibition of the esterase activity. Short-term exposure produced significant inhibition in oxygen uptake, with lower damage to enzymatic activity. Median effect values for oxygen uptake inhibition were 64±13mgL−1 and 0.32±0.07mgL−1 for ibuprofen and triclosan respectively using 125mgL−1 activated sludge. For the inhibition of enzymatic activity values were 633±63mgL−1 for ibuprofen and 1.94±0.32mgL−1 for triclosan. Results indicated that oxygen uptake, related to primary activity of microorganisms, was more strongly affected than the enzymatic activity associated to energy consumption. Toxicity interactions were determined using the Combination Index-isobologram method. Results showed antagonism at lower values of affected population, after which the mixtures tended to additivity and synergism. For the case of enzymatic activity, the antagonism was less marked and the additivity range was higher.