Analgesic-antipyretic Drug Research Articles

Analisa mutu tablet ibuprofen generik berlogo dan generik bermerek yang diproduksi industri X di Gresik

Ibuprofen tablets are one of the most widely used antipyretic analgesic drugs for self-medication in pharmacies. According to the Biopharmaceutical Classification System (BCS), Ibuprofen is included in Class II or drugs with low solubility, but high permeability. This study was carried out to determine the physical quality of branded generic and branded generic ibuprofen drugs. This research was carried out by dissolution testing on ibuprofen tablets. The results obtained from the physical quality test met the specified requirements. The dissolution test showed that Q30 had dissolved more than 70%. The conclusion is that the drug meets the requirements and there is no difference between generic drugs with the logo and branded generics.

Differences In Destruction Time and Determination of Generic and Trademark Paracetamol Tablets Using UV Spectrophotometry Method

Paracetamol is one of the most widely used antipyretic analgesic drugs in the community. Paracetamol in circulation, both generic and trademarked, is generally given in the form of tablets containing 500 mg of the active ingredient. At this time people prefer to use trademarked paracetamol tablets with the assumption that trademarked drugs are more efficacious than generic drugs. This study aims to determine the difference in disintegration time and content of generic paracetamol tablets with trademarks. The study was conducted on 2 samples of generic paracetamol tablets with 2 samples of paracetamol tablets of different brands. The results of the disintegration time test showed that the average of generic A paracetamol tablets was 8.41 minutes, generic B 1.2 minutes, trademark A 2.14 minutes, trademark B 1.2 minutes. While the results of the average level test obtained paracetamol tablets generic A 109.87% generic B 105.95% trademark A 103.28% trademark B 92.49% with categories according to the standards set in the literature. The results of the Paired Sample T-test on disintegration time obtained a value of 0.006 and the results on the level test of 1.00 so that it can be concluded that between generic and trademarked paracetamol tablets only have differences in disintegration time with the same concentration.

Analgesic and Antipyretic Activity of Sweet Orange Peel Methanol Extract

An analgesic-antipyretic drug widely used is paracetamol, which has various health benefits and several adverse effects. Therefore, various natural products have been extensively studied as alternative analgesic-antipyretics, one of which is sweet orange peel. This study aimed to investigate sweet orange peel's analgesic and antipyretic activity by in vivo methods. This experimental study evaluated the analgesic and antipyretic effects of sweet orange peel extract extracted by the maceration method. The analgesic effect was evaluated by tail immersion (Maximum Possible Analgesia) and acetic acid-induced writhing method (total abdominal writhing). Meanwhile, the antipyretic effect was evaluated by the brewer yeast-induced hyperpyrexia (body temperature) method. This study showed that sweet orange peel methanol extract significantly increased the maximum possible analgesia value (132.79%) and reduced the number of abdominal writhing (44.05%) at the highest dose of 750 mg/kg BW. It indicated analgesic activity from sweet orange peels. Meanwhile, the antipyretic effect of sweet orange peel methanol extract was observed from 1-4 hours after administration, and the highest percentage inhibition of body temperature 4 hours after administration was found in a moderate dose, that was 5.98% (P value: 0.042). Therefore, it can be concluded that sweet orange peel methanol extract has analgesic and antipyretic effects with an optimal dose range of 500-750 mg/kg BW.

EVALUASI UPAYA PENGOBATAN SENDIRI (SWAMEDIKASI) MENGGUNAKAN OBAT ANALGETIKA-ANTIPIRETIKA PADA MASYARAKAT DESA JERUJU BESAR KALIMANTAN BARAT

Self-medication requires a good knowledge in order to run well. This study was conducted to determine the relationship and strength of the relationship in the selection of antipyretic analgesic drugs associated with age, education and occupation by the people of Jeruju Besar Village. This type of research is non-experimental with a questionnaire tool. Sampling using purposive sampling method. Respondents in this study were 378 respondents. The results showed that the people of Jeruju Besar Village were right in choosing the medicine for fever, headache and pain. Respondents received information on drug selection through health workers by 58.7% and the reasons for self-medication to recover quickly were 74%. The majority of respondents aged 40 years 52.6%, while the level of education is moderate - high 52.4%. Based on the Multiple Correlation test the strength of the relationship was obtained Perfect Correlation or perfect knowledge (0.981) and education (0.872), Strong Correlation occupation (0.698) and age (0.633). The conclusion of this study is that there is a relationship between the level of education, knowledge, on the use of antipyretic analgesic drugs.

Investigation of the Protective Effects of Urtica dioica, Capsella bursa-pastoris and Inula racemosa on Acetaminophen-Induced Nephrotoxicity in Swiss Albino Male Mice

Acetaminophen (APAP) is the most commonly used nonprescription antipyretic-analgesic drug. This medication is thought to be safe at the suggested dosage (4 g/24 h), but its overdose (up to 2.5 g/kg) can cause severe injuries to the human body, including renal injury. APAP has various toxic effects on nephrons, as it leads to an excessive free radical generation that, in turn, results in a disturbance in the redox homeostasis of cells, causing oxidative stress. To replenish this oxidative stress, there is an ultimate urge for natural therapies that can retain the cellular homeostasis of nephrons by diminishing the overdose impression of acetaminophen. The principle objective of this work is to appraise nephrotoxicity due to APAP and its amelioration through the antioxidant properties of aqueous extracts of selected medicinal plants: Urtica dioica, Capsella bursa-pastoris, and Inula racemosa (UD, CBP, and IR, respectively). The pH stability of the nutraceuticals used was examined by determining the impact of pH 4, pH 7 and pH 9 on the DPPH radical scavenging activity of aqueous plant extracts. Gas chromatography-Mass spectroscopy (GC–MS) analytical technique was performed to determine the volatile organic phytochemical profiles of all three medicinal plants. Male Swiss albino mice were used for the present investigation. The animals were distributed into five groups of (n = 6), a total of 30 mice, for in vivo analysis. Group 1 served as the control group; group 2 received a single IP dose of APAP (600 mg/kg); group 3 received APAP pretreated with UD (300 mg/kg); group 4 received APAP pretreated with CBP (300 mg/kg); and group 5 received APAP pretreated with IR (300 mg/kg). Overdose of the APAP- induced a significant (p < 0.05) alterations in the total protein concentration, weight and the nephrological architecture in renal tissue, as observed through biochemical assays and histopathological examinations. Due to nephrotoxicity, there was a substantial (p < 0.05) drop in body weight and total protein contents in the APAP alone group when compared to the treatment groups. There was remarkable protection against APAP-induced alterations in the total protein of renal homogenate in the treatment groups. Histopathological analysis (H&E staining) of the mice kidneys indicated severe deterioration in the APAP alone group, whereas the therapy groups showed considerable nephroprotection towards APAP-induced abnormalities. The biochemical findings and histopathological study of the kidneys revealed that the herbal extracts (UD, CBP, and IR) have a nephroprotective potential against APAP-induced nephropathy. The trend of efficacy was observed as UD > CBP > IR. However, extensive study is needed to determine the likely ameliorative mechanism of these nutraceuticals.

Pengaruh Variasi Konsentrasi Chitosan Sebagai Bahan Penghancur Terhadap Sifat Fisik Sediaan Orally Disintegrating Tablet (ODT) Paracetamol

An antipyretic analgesic drug called paracetamol is used in children to treat mild to moderate pain and fever. Orally Disintegrating Tablet (ODT), a medicine that dissolves in seconds, was created to help children who have difficulty swallowing tablets. The purpose of this study was to determine the effect of changes in the concentration of chitosan as a disintegrant in the formulation of ODT paracetamol. These ODT tablets are made using a wet granulation process. Paracetamol ODT tablets were produced in three formulations with 3.5% chitosan concentration; 7% and 14%. The findings showed that the optimal concentration of chitosan was 3.5%, which had an impact on the physical characteristics and dissolution of tablets. The results showed that paracetamol F1 ODT preparation with 3.5% chitosan concentration was the best formula. This was caused by chitosan with an average weight uniformity test value of 202.65±2.00 mg; uniformity of diameter and thickness 0.831±0.008 cm and 0.343±0.008 cm, hardness 5.4±0.34 kg; brittleness 0.23±0.02; disintegration time 24 seconds; da dissolution 99.56%. The findings for hardness (p= 0.011), friability (p= 0.046), and disintegration time (p= 0.000) all showed significant variation (p 0.05). It was concluded that the disintegration time of the tablets increased with the increase in the chitosan content. It is recommended that further research be conducted for analgesic and antipyretic tests to determine whether the tablets have an effective analgesic and antipyretic effect.

Ulva fasciata, a green alga, attenuates the kidney and liver dysfunctions in rats induced by acetaminophen

Acetaminophen (AAP) is an analgesic–antipyretic drug which is considered safe at recommended dose, but its overuse may induce renal and hepatic injuries. Marine macro algae have great potential against drug-induced renal and hepatic dysfunctions. The present study described the reno-protective and hepato-protective effects of the ethanol extract of an edible green alga Ulva fasciata and its fractions (n-hexane, chloroform and methanol) against AAP toxicity. In the 1st set of experiment, rats were divided into five groups. Of which two were treatment groups beside three controls, the first treatment group was given ethanol extract of U. fasciata alone and the second group was given the same extract with AAP. In the 2nd set of experiment, rats were divided into nine groups, of which three treatment groups administered n-hexane, chloroform and methanol fractions of ethanol extract of U. fasciata respectively while other three treatment groups received the same fractions individually with AAP. On the 11th day, rats were decapitated after 12 h of fasting from both sets, blood samples were collected for assessment of biochemical parameters and kidney tissues were used for determination of oxidants and antioxidants. Histopathological assessment was also done in kidney tissues. A single dose of AAP (600 mg/kg) affected kidney markers including creatinine, urea and blood urea nitrogen (BUN) and hepatic enzymes. Ethanolic extract of U. fasciata normalized kidney and liver markers in AAP intoxicated rats. AAP also reduced glutathione (GSH) in kidney tissues and altered kidney architecture, which were improved by ethanolic extract and chloroform soluble fraction of U. fasciata. A total of 14 polyunsaturated fatty acids were identified from chloroform soluble fraction of U. fasciata by GC-MS and assumed these may be involved in protective activities of U. fasciata.

Validated HPLC–PDA methodology utilized for simultaneous determination of Etoricoxib and Paracetamol in the presence of Paracetamol toxic impurities

Etoricoxib (ETO), Paracetamol (PCM), and two toxic impurities for Paracetamol impurity K (4-aminophenol (PAP)) and impurity E (para-hydroxy acetophenone (PHA)) were separated using a simple and selective HPLC method that was tested for the first time. PCM is a commonly used analgesic and antipyretic medication that has recently been incorporated into COVID-19 supportive treatment. Pharmaceuticals containing PCM in combination with other analgesic-antipyretic drugs like ETO help to improve patient compliance. The studied drugs and impurities were separated on a GL Sciences Inertsil ODS-3 (250 × 4.6) mm, 5.0 µm column, and linear gradient elution was performed using 50 mM potassium dihydrogen phosphate adjusted to pH 4.0 with ortho-phosphoric acid and acetonitrile as mobile phase at 2.0 mL/min flow rate at 25 °C and UV detection at 220 nm. The linearity range was 1.5–30.0 µg/mL for ETO and PCM while 0.5–10.0 µg/mL for PAP and PHA, with correlation coefficients (r) for ETO, PCM, PAP, and PHA of 0.9999, 0.9993, 0.9996, and 0.9998, respectively. The proposed method could be used well for routine analysis in quality control laboratory.

Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway.

Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is a traditional nonsteroidal antipyretic analgesic and anti-inflammatory drug commonly used in clinic, which has inhibitory effect on colorectal cancer, gastric cancer, and other malignant tumors. This study showed that Celecoxib could significantly reverse the invasion and metastasis of gastric cancer and improved the pathological changes due to GC. We collected the clinical specimens to analyze the correlation between the expression of Lnc_AC006548.28, miR-223, and LAMC2. In the mouse model, Celecoxib can slowdown the growth of GC tumor and the occurrence of this effect may depend on Lnc_AC006548.28-miR-223-LAMC2 pathway, in vitro transfection, RT-PCR, western blot, CCK8, small chamber assay, flow cytometry, and immunohistochemistry to retest the protective effect of celecoxib. Our results showed that Celecoxib could reverse invasion and metastasis of gastric cancer through Lnc_AC006548.28-miR-223-LAMC2 pathway.

THE IDENTIFICATION AND STUDY OF HERBAL MEDICINE (JAMU) FRAGMENTATION PATTERNS CONFIRMED ACETAMINOPHEN BY USING LIQUID CHROMATOGRAPHY MASS SPECTROSCOPY (LCMS)


 In the last twenty years, many of jamu or herbal medicine were adulterated with chemical drugs. One of the chemical drugs that is commonly added to herbal medicine is acetaminophen. Acetaminophen is generally considered as an analgesic-antipyretic drug. The sample of this study consisted of 6 samples of jamu or herbal medicine with different brands. Qualitative analysis was conducted by TLC method using the mobile phase n-hexane: ethyl acetate (1:1), it was obtained three positive samples containing acetaminophen, namely sample D, E, and F. The three positive samples containing acetaminophen were calculated using the LCMS method. Quantitative analysis was conducted with LCMS using a reversed-phase with a mobile phase of acetonitrile: water (15%>: 85%> v/v) at a flow rate of 0.2 mL/min and an injection volume of 5 gL, it was obtained the levels of acetaminophen in sample D as much as 0.16 g/2 g of sample, in sample E of 0.63 g/7 g of sample, and in sample F of 0.56 g/7 g of sample. Although the content of acetaminophen in herbal medicine is relatively small, but according to the Regulation of the Minister of Health of Indonesia No. 007 of 2012, traditional medicine or herbal medicine should not contain synthetic chemicals.

Profil Penggunaan Obat dalam Swamedikasi pada Ibu-Ibu PKK di Kecamatan Garut Kota

Self-medication is an independent treatment that carried out to deal with minor complaints by only using over-the-counter drugs that are limited. Self-medication is commonly used by the mothers to treat their families when they suffering from pain. If self-medication done properly, it can be a big contribution to the government, especially to maintaining national health. However, self-medication will be at risk if the treatment is done incorrectly. The study was conducted using a descriptive observational study method by giving a posttest questionnaire and pretest to assess medicine use and habits in self-medication to 50 PKK mothers in Garut sub-district, Garut Regency. The results of the study showed that the highest number of self-medication was fever and ulcer (26%), the type of drug that they used was modern medicine (70%), the choice of drugs used were antipyretic analgesic drugs (44%). Wilcoxon test indicates that there is a significant influence after giving counseling to the choice of habitual answers in self-medication for respondent (p<0.05).

Hepatoprotective activity against acetaminophen-induced liver dysfunction and GC-MS profiling of a brown algae Sargassum ilicifolium

BackgroundDrug-induced hepatotoxicity is one of the most important causes of liver dysfunction. Acetaminophen (paracetamol) an analgesic-antipyretic drug is generally considered safe but its overdose may cause liver toxicity. Marine macro-algae (seaweeds) especially brown seaweeds possess unique biological activities including hepatoprotective potential. The current study focused on the hepatoprotective effect of different solvent fractions of Sargassum ilicifolium and characterization of its n-hexane soluble fraction.MethodsThe ethanol extract (20 g) of S. ilicifolium was mixed with solvents of increasing polarity, starting with n-hexane followed by chloroform and methanol. All three (n-hexane, chloroform and methanol) soluble fractions were administered to the rats at dose of 150 mg/kg, b.w. Intraperitoneal administration of acetaminophen (600 mg/kg b.w.) to rats was used to cause liver injury. The hepatic damage was evaluated by liver markers enzymes; aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin along with other metabolites i.e., triglycerides, cholesterol, urea, glucose and creatinine. Lipid peroxidation and glutathione and were estimated in liver tissue. n-Hexane fraction was subjected to GC-MS analysis in order to identify potent compounds.ResultsThe oral administration of n-hexane and methanol soluble fractions reduced the acetaminophen-augmented liver marker enzymes ALT, AST, ALP, LDH, along with bilirubin, urea, creatinine, glucose and triglycerides. The n-hexane and methanol soluble fractions also improved hepatic antioxidant level via enhancing hepatic glutathione and reversing lipid peroxidation. GC-MS spectroscopy of n-hexane fraction of S. ilicifolium revealed the presence of some new compounds. Among them, fatty acids were found to be in highest concentration followed by halogenated hydrocarbons, benzene derivatives, and sterols. Fatty acid in seaweed may be one of the factors for hepatoprotection from drug-induced hepatotoxicity.ConclusionFrom the results, it is evident that n-hexane and methanol soluble fractions of S. ilicifolium have the ability to protect the liver against toxicity, which is comparable with silymarin used as a standard drug. Sargassum ilicifolium contains bioactive compounds with pharmaceutical importance.

AMELIORATIVE EFFECTS OF HESPERIDIN AND MELATONIN AGAINST ACETAMINOPHEN-INDUCED NEPHROTOXICITY IN ADULT ALBINO RATS

ABSTRACT Background: Acetaminophen (APAP) is the most widely used analgesic antipyretic drug, either by prescription or over the counter. APAP overdose can damage multiple organs, especially the liver and kidney due to the formation and clearance of its toxic metabolites. Aim: To investigate and compare the ameliorative effects of hesperidin (HSP) and melatonin (MEL) in rats with APAP-induced nephrotoxicity. Methodology: This comparative experimental study was carried out on 72 adult male Wistar albino rats were divided into nine groups (eight/each): groups (1-5): controls “negative, solvent, N-acetyl cysteine (NAC), MEL and HSP respectively; group (6): APAP-nephrotoxicity “rats were given a single dose (900 mg/kg) of APAP intraperitoneally (i.p.); group (7): APAP+NAC (150mg/Kg); group (8): APAP+MEL (10mg/Kg) and group (9): APAP+HSP (200mg/Kg). All treated drugs (NAC, MEL, and HSP) were given i.p. 30 minutes before APAP administration. Renal blood flow (RBF), blood urea, serum creatinine, tissue malondialdehyde (MDA), reduced glutathione (GSH), tumor necrotic factor alfa (TNF-α), and interleukin-6 (IL-6) were estimated by colorimetric methods. Immunohistochemical expression of inducible nitric oxide synthase (iNOS) was detected and histopathological examination of renal tissue specimens was performed. Results: HSP; MEL and NAC partially improved APAP-induced nephrotoxicity, evidenced by biochemical, histopathological, and immunohistochemical findings. Conclusion: Both HSP and MEL alleviated APAP-induced nephrotoxicity, however, HSP was superior to MEL and it was as equal as NAC (which was also superior to MEL) as regards the tested parameters. The ameliorative effects of HSP and MEL may be at least in part due to their antioxidant and anti-inflammatory properties.

Ethenzamide Exerts Protective Effects against Ibuprofen-Induced Gastric Mucosal Damage in Rats by Suppressing Gastric Contraction.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage, in which gastric hypermotility has been reported to play a primary role. The antipyretic analgesic drug ethenzamide (ETZ) is widely used in combination with other NSAIDs and, in a recent study, was found to possess 5-hydroxytriptamine (5HT)2B receptor antagonistic activity. Therefore, the inhibition of gastric contraction via 5HT2B receptor blockade by ETZ might contribute to ETZ's protective effect against NSAIDs-induced gastric mucosal damage. In the present study, we examined the effects of ETZ on gastric contraction and ibuprofen (IBP)-induced gastric mucosal damage in rats. We found that ETZ suppressed both 5HT- and α-methyl-5HT (5HT2 receptor agonist)-induced contractions of rat-isolated gastric fundus in a concentration-dependent manner. This suppressive effect of ETZ was not seen for either high-KCl- or acetylcholine-induced contractions. Furthermore, ETZ was confirmed to decrease ibuprofen-induced gastric mucosal damage in a dose-dependent manner in rats. Similarly, clonidine is known to reduce gastric motility, and methysergide (a 5HT2 receptor antagonist) is known to inhibit 5HT-induced contractions of the gastric fundus, which also decreases IBP-induced gastric mucosal damage, respectively. Although further research on other possible sites or mechanisms of action would be needed, these results suggest that ETZ exerts a protective effect against IBP-induced gastric mucosal damage and that suppressing the gastric contraction may play an important role in the gastroprotective effect of ETZ.

The role of topical therapy in the treatment of acute otitis media in children

Acute otitis media is a common disease in children and accounts for about 2% of the total child morbidity. In the largest percentage of cases, acute otitis is usually successfully resolved, but its relapses increase the possibility of complications and lead to higher treatment costs, as well as lower quality of life for both the patient and his or her family in general. Therapy of acute otitis media depends on the stage of disease development and clinical manifestations and is aimed at early resolution of inflammatory process and prevention of disease progress and complications development. Pathogenetic therapy is shown at the 1 st and 2 nd stages of development of acute otitis media and is based on restoration of auditory tube function and normalization of nasal breathing (unloading – intranasal therapy). As a local analgesic therapy for acute otitis media in children, ear drops containing non-opioid analgesic antipyretic drug phenazone and lidocaine, consisting of a combination of phenazone (40 mg) and lidocaine hydrochloride (10 mg), are most commonly used. Phenazone is a nonsteroidal anti-inflammatory drug and has an anti-inflammatory effect, typical for non-selective inhibitors of cyclooxygenase, while lidocaine has a local analgesic effect. Based on the clinical trials conducted, it was recommended to include combined topical drugs as a local analgesic and anti-inflammatory drug with effective action and good tolerability in all age groups into the combined therapy of acute preperforative otitis media.

Analysis of three antipyretic analgesic drugs by open-tubular capillary electrochromatography

The advantages of capillary electrophoresis, such as small sample consumption, high separation efficiency, and multiple separation modes, have been known for decades. However, exploring unique capillary electrophoresis techniques for the analysis of fluid drugs in living bio-systems remains an important and urgent task. Owing to the similar structures and mass-to-charge ratios of antipyretic analgesic drugs, efficient baseline separation of these analytes by capillary zone electrophoresis method cannot be easily achieved. Micellar electrokinetic chromatography can improve the baseline separation of these drugs, but the substantial amounts of non-volatile surfactants (such as sodium dodecyl sulfate, sodium dodecyl sulfonate, sodium deoxycholate and cetylammonium bromide) in running buffer solutions would pollute the ion source during mass spectrometric analysis. For this reason, it is difficult to analyze unknown drugs by capillary electrophoresis-electrospray ionization-mass spectrometry. To overcome these drawbacks, much attention has been paid to capillary electrochromatography (CEC) because combines the high separation efficiency of capillary electrophoresis with the high selectivity of high performance liquid chromatography (HPLC). Recent challenges encountered in open-tubular capillary electrochromatography (OT-CEC) expanding the range of suitable functional polymer monomers and improvement of the separation efficiency by tuning the characteristics of the polymer coatings without using any organic solvent additives. In this study, a protocol based on OT-CEC using a block co-polymer coating is proposed for the analysis of three test antipyretic analgesic drugs (4-aminoantipyrine, antipyrine and phenacetin), without adding organic solvents and surfactants in the running buffer solutions. First, an amphiphilic block co-poly(styrene-co-glycidyl methacrylate) (P(St-GMA)), was synthesized by reversible addition-fragmentation chain transfer polymerization under mild conditions. Then, P(St-GMA) was coated onto the capillary surface, and an OT-CEC analysis was performed. Next, the effect of some key factors, including the polymerization time for obtaining P(St-GMA) with different molecular weights, coating concentrations of the block copolymer, the species of the running buffer solutions, pH and concentrations of the running buffer solutions, and organic solvent additives, on the OT-CEC separation efficiency were investigated. Under the optimized conditions with 50.0 mmol/L NaAc-HAc as the running buffer solution at pH 5.7, the three test antipyretic analgesic drugs were base-line separated by the constructed OT-CEC system. Good linear relationships between peak area and concentration of the test analytes in the range of 8.0-2.5×103 μmol/L were obtained (R2 ≥ 0.995). The limits of detection (LODs) were 1.0-2.5 μmol/L. Furthermore, the reason for the OT-CEC separation efficiency was clarified based on the decreased electro-osmotic flow in the coated capillary compared with that in the uncoated capillary. Finally, the proposed OT-CEC assay without using any organic solvents and surfactants as additives was applied for analysis of the three test antipyretic analgesic drugs in rat serum samples. Importantly, it was found that despite peak tailing, the OT-CEC separation efficiency of the drugs was dramatically enhanced because the block co-polymer could self-assemble in the solution and form pseudo-micelles, which further increased the interactions between the P(St-GMA) and these drugs. Our results not only reveal the great potential of block co-polymer coatings in OT-CEC for the analysis of drugs in real biological samples, but also serve asa platform for the preparation of diverse block co-polymers to be used in OT-CEC analysis. We believe that in the near future, the peak tailing problem in OT-CEC analysis can be resolved by using the designed unique block co-polymers, which possess a greater number of functional sites, as coatings and by appropriately tuning the interactions between the analytes and the coatings.

Detoxification and bioaugmentation potential for acetaminophen and its derivatives using Ensifer sp. isolated from activated sludge

Acetaminophen (APAP), a widely used analgesic–antipyretic drug, is frequently detected in the environment and may pose ecological risks to aquatic communities. In this work, an APAP-degrading organism, designated as Ensifer sp. POKHU, was isolated from activated sludge (AS) enriched with APAP. POKHU degraded up to 630 mg/L of APAP without substrate inhibition. The bacterium metabolized APAP to hydroquinone (HQ) via 4-aminophenol (4-AP). APAP derivatives, 4AP, HQ, and 1,4-benzoquinone (BQ), frequently detected in the environment, were found to inhibit nitrogen metabolism (ammonium oxidation) to a greater extent than APAP. POKHU had the ability to degrade varying levels (0.4–40 mg/L) of 4-AP, HQ, and BQ, which indicated a great potential for detoxification in environments contaminated with both APAP and its derivatives. The addition of POKHU to fresh AS samples taken from a wastewater treatment plant greatly increased the biotransformation rates of APAP from 5.6 d−1 (no POKHU augmentation) to >20.0 d−1 (5% POKHU). Bioaugmentation with POKHU reduced 400 μg/L of APAP to levels below its ecotoxicity threshold within 4 h, which is shorter than the typical hydraulic retention times for full-scale AS processing. Overall, this study identified a new auxiliary biological agent for APAP detoxification, which could degrade both APAP and its metabolic derivatives (those that can be more toxic than the parent contaminant, APAP). The results have practical implications for developing a biological means (detoxification and bioaugmentation) of treating high-strength pharmaceutical waste streams, such as wastewater from hospitals and drug manufactures, and of landfill leachates.

Omega-3 fatty acids protect against acetaminophen-induced hepatic and renal toxicity in rats through HO-1-Nrf2-BACH1 pathway

Although acetaminophen (APAP) is a commonly used analgesic antipyretic drug, hepatotoxicity and nephrotoxicity are common after the overdose. The main mechanism of APAP toxicity is oxidative stress based. Stress may induce the production of heme oxygenase 1 (HO)-1 which is regulated by interleukin (IL)-10 and inhibit the production of tumor necrosis factor-alpha (TNF-α). HO-1 expression is further regulated by nuclear factor erythroid 2–related factor 2 (Nrf2) and the transcription factor BTB and CNC homology 1 (BACH1). Drug-induced toxicity can be relieved by several natural products, which are preferred due to their dietary nature and less adverse reactions. Of these natural products, omega-3 (ω-3) fatty acids are known for anti-inflammatory and antioxidant actions. However, effects of ω-3fatty acids on APAP-induced hepatic and renal toxicity are not well addressed. We designed this study to test the potential protecting actions of ω-3 fatty acids (270 mg/kg Eicosapentaenoic acid and 180 mg/kg docosahexaenoic acid, orally, for 7 days) in hepatotoxicity and nephrotoxicity induced by APAP (2 g/kg, once orally on day 7) in rats. Moreover, we focused on the molecular mechanism underlying APAP hepatotoxicity and nephrotoxicity. Pre-treatment with ω-3 fatty acids enhanced liver and kidney functions indicated by decreased serum aminotransferases activities and serum creatinine and urea concentrations. These results were further confirmed by histopathological examination. Moreover, ω-3 fatty acids showed antioxidant properties confirmed by decreased malondialdehyde level and increased total antioxidant capacity. Antioxidant Nrf2, its regulators (HO-1 and BACH1) and the anti-inflammatory cytokine (IL-10) were up-regulated by APAP administration as a compensatory mechanism and they were normalized by ω-3 fatty acids. ω-3 fatty acids showed anti-inflammatory actions through down-regulating nuclear factor kappa B (NF-ĸB) and its downstream TNF-α. Moreover, Western blot analysis showed that ω-3 fatty acids promoted Nrf2 translocation to the nucleus; BACH1 exit from the nucleus and inhibited NF-ĸB nuclear translocation. These findings suggested the protecting actions of ω-3 fatty acids against APAP-induced hepatic and renal toxicity through regulation of antioxidant Nrf2 and inflammatory NF-ĸB pathways.

Structural modification of aspirin to design a new potential cyclooxygenase (COX-2) inhibitors.

Aspirin (Asp) is one of the most important and ancient member of nonsteroidal anti-inflammatory drugs (NSAID), commonly used in medication of fever, pain and inflammation. It can inhibit the synthesis of prostaglandin by blocking the cyclooxygenase (COX). Attempts have been taken to analyze aspirin together with some of its modified derivatives applying quantum mechanical calculations in order to compare their physicochemical and biochemical properties. Density functional theory (DFT) with B3LYP/6-31G (d, p) basis set has been employed to elucidate their thermal, molecular orbital, equilibrium geometrical properties in gas phase. Molecular docking and nonbonding interactions have been performed against human cyclooxygenase-2 protein 5F1A to investigate the binding affinity and mode(s) of newly designed aspirin derivatives. ADMET prediction has been utilized to compare the absorption, metabolism, and carcinogenic properties of new derivatives with parent drug (Asp). Thermal and geometrical results support the thermochemical stability and equilibrium geometry of all the structures. From the molecular docking simulation, most of the derivatives exhibited better binding affinity than parent drug (Asp) with the receptor protein (5F1A). ADMET prediction disclosed the improved pharmacokinetic properties with lower acute oral toxicity of some derivatives. Based on quantum chemical, molecular docking and ADMET analysis, this investigation can be useful to understand the physicochemical and biochemical/biological activities of Asp and its modified derivatives to search a new antipyretic analgesic drug.

JNK Signaling Pathway Mediates Acetaminophen-Induced Hepatotoxicity Accompanied by Changes of Glutathione S-Transferase A1 Content and Expression.

Acetaminophen (APAP) is an analgesic–antipyretic drug and widely used in clinics. Its overdose may cause serious liver damage. Here, we examined the mechanistic role of c-Jun N-terminal kinase (JNK) signaling pathway in liver injury induced by different doses of APAP. Male mice were treated with APAP (150 and 175 mg·kg−1), and meanwhile JNK inhibitor SP600125 was used to interfere APAP-induced liver damage. The results showed that JNK signaling pathway was activated by APAP in a dose-dependent manner. C-Jun N-terminal kinase inhibitor decreased JNK and c-Jun activation significantly (P < 0.01) at 175 mg·kg−1 APAP dose, and phosphorylation levels of upstream proteins of JNK were also decreased markedly (P < 0.05). In addition, serum aminotransferases activities and hepatic oxidative stress increased in a dose-dependent manner with APAP treatment, but the levels of aminotransferases and oxidative stress decreased in mice treated with JNK inhibitor, which implied that JNK inhibition ameliorated APAP-induced liver damage. It was observed that apoptosis was increased in APAP-induced liver injury, and SP600125 can attenuate apoptosis through the inhibition of JNK phosphorylation. Meanwhile, glutathione S-transferases A1 (GSTA1) content in serum was enhanced, while GSTA1 content and expression in liver reduced significantly with administration of APAP (150 and 175 mg·kg−1). After inhibiting JNK, GSTA1 content in serum decreased significantly (P < 0.01); meanwhile, GSTA1 content and expression in liver enhanced. These findings suggested that JNK signaling pathway mediated APAP-induced hepatic injury, which was accompanied by varying GSTA1 content and expression in liver and serum.