Dose Of Diclofenac Research Articles

Assessment of use and Awareness of Diclofenac in Syria

Diclofenac, known as diclone in Syria, is the most widely used drug in multiple medical conditions. This research was conducted to assess the use and awareness of diclofenac in Syria through a survey. 601 responses were included in this research.Most participants were female (67.7%), between the ages of 18 and 30 years (82.9%), and did not have a chronic disease (86.3%). More than half of the participants were university students (53.4%). A high proportion of the participants had a university education level (87.7%). The most commonly used dosage form for diclofenac was tablets among participants(70.9%). 43.8% chose 50mg as the dose of diclofenac. Most participants improved after using diclofenac (73.7%). Participants were satisfied after diclofenac treatment (66.56%). Most had no side effects after treatment with diclofenac (79.5%). 81.3% of the participants who experienced side effects suffered from stomach pain. Fortunately, 84.4% of the participants did not use the injection combining diclofenac with cortisone and an antibiotic. 56.38% used this combination to treat respiratory infections. A minority of the participants experienced allergic reactions after taking this medication (4%). More than two-thirds of the participants will continue to use diclofenac for pain management in the future (65.9%).77.9% of the participants used diclofenac without a prescription. Most participants used this medicine after a meal (82%). 36.6% of the participants recorded half an hour as the onset of diclofenac. The participants reported an action duration of 6 hours (24.5%) and 8 hours (31%). This study confirmed the high use of diclofenac among the Syrians. A good level of awareness was observed among the surveyed participants.

Anti-inflammatory and anti-arthritic activities of ethanolic extract of Myxopyrum serratulum A.W. Hill

BackgroundRheumatoid arthritis (RA) is a debilitating inflammatory disorder characterized by an overactive immune system targeting joints, leading to inflammation and intense pain. While current RA therapies effectively alleviate symptoms, they are often associated with significant side effects. This study aimed to assess the anti-inflammatory and anti-arthritic properties of an Ethanolic Extract of Myxopyrum serratulum A.W. Hill (EEMS) using animal models.ResultsThe acute toxicity study with EEMS (2000 mg/kg, p.o.) on rats showed no toxicity or mortality up to the highest dose. Inflammation was induced using carrageenan, and rats were treated with varying doses of EEMS (100, 200, and 400 mg/kg, p.o.) and diclofenac to assess anti-inflammatory effects. Anti-arthritic efficacy was evaluated using Complete Freund’s adjuvant (CFA)-induced inflammation, comparing EEMS to methotrexate. The results revealed dose-dependent anti-inflammatory effects of EEMS and a reversal of arthritic-induced weight loss in treated groups. Paw volume reduction was significant in both EEMS and methotrexate groups. Biochemical analyses showed elevated markers in the arthritic control group, which were normalized by EEMS and methotrexate. Notably, EEMS (400 mg/kg) significantly reduced cathepsin-D levels compared to the positive control. EEMS administration also lowered hepatic lipid peroxidation and increased endogenous antioxidants (SOD, GSH, and GPX). The 200 and 400 mg/kg doses reduced the iNOS/GADPH ratio, while the 400 mg/kg dose restored cellular and joint structure and significantly decreased IL1 levels.ConclusionsIn conclusion, EEMS demonstrated substantial protective effects, mitigating health risks associated with chronic inflammation such as arthritis. These findings underscore the ethnomedical potential of Myxopyrum serratulum as a promising anti-inflammatory and anti-arthritis agent. The study suggests that EEMS could be a viable alternative or complementary therapy for RA, offering therapeutic benefits with potentially fewer side effects than current treatments.

The Clinical Effectiveness of Transcutaneous Electrical Nerve Stimulation on Enhancing Recovery after Cesarean Section: A Systematic Review and Meta-Analysis

Background: The transcutaneous electrical nerve stimulation TENS was used following several surgical procedures involving gynecological ones and has shown a successful pain reduction rate. TENS was proposed to enhance recovery after cesarean section CS. Objective: This systematic review and meta-analysis were conducted to evaluate the clinical effectiveness of Transcutaneous electrical nerve stimulation TENS in enhancing recovery after a cesarean section. Methods: We performed the Meta-analyses using RevMan software. Data were pooled as mean difference (MD) if continuous and risk ratio (RR) if dichotomous, and the 95% confidence interval (CI) as calculated. Results: This systematic review included 12 RCTs, with a total of 1,116 women studied. The TENS effectively reduced the intensity of pain just by following its application (SMD=-0.61; 95% CI [-0.82, -0.39], P<0.00001), one day after (SMD=-0.25; 95% CI [-0.47, -0.04], P=0.02), and two days after (SMD=-0.27; 95% CI [-0.50, -0.03], P=0.03). Conclusion: The TENS effectively reduces the pain intensity following its application and after one or two days. TENS has no effect on the cumulative dose of diclofenac. Because of the inadequacy of safety data, we recommend conducting further RCTs.

Experimental study of the anti-inflammatory activity of diclofenac in ultra-low doses on a model of acute carrageenan inflammation

Experimental study of the anti-inflammatory activity of diclofenac in ultra-low doses on a model of acute carrageenan inflammation

Protective role of melatonin against diclofenac-induced acute kidney injury

Diclofenac (DF), a non-steroidal anti-inflammatory drug, is commonly used to relieve pain and inflammation. High doses of DF might induce acute kidney injury (AKI), particularly in elderly, a known vulnerable population. AimWe aimed to assess the protective role of melatonin (Mel) on DF-induced AKI in aged rats and to highlight the underpinning mechanisms include, oxidative stress and inflammation focusing on microRNA-34a (miR-34a), nuclear factor erythroid-2-related factor-2/hemeoxygenase-1 (Nrf2/HO-1) and NLR family-pyrin domain containing-3 (NLRP3) inflammasome pathways, and to elucidate the possibility of epithelial sodium channel (ENaC) involvement. Materials and methodsThirty old male Wistar rats were allocated randomly into 3 groups: Control, DF and Mel-DF groups. Key findingsMelatonin provided nephroprotective effects against DF-induced AKI via attenuating the expression of renal miR-34a and subsequently promoting the signaling of Nrf2/HO-1 with elevation of the antioxidant defense capacity and suppressing NLRP3 inflammasomes. Melatonin alleviated DF-induced hypernatremia via decreasing the ENaC expression. Renal histopathological examination revealed significant reduction in vascular congestion, mononuclear infiltration, glomerulo-tubular damage, fibrosis and TNF-α optical density. SignificanceIt can be assumed that melatonin is a promising safe therapeutic agent in controlling DF-induced AKI in elderly.

Self-induced Anuria with Diclofenac: An Interesting Case of “Quadruple Whammy” Acute Kidney Injury

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of drugs widely prescribed and used worldwide. Patients taking NSAIDs, including diclofenac, should be aware of its potential nephrotoxic effects. However, the rapid onset of acute kidney injury (AKI) after a single dose of diclofenac is considered a very rare side effect. Case Presentation: We present a 66-year-old woman with habitual self-induced anuria with the chief complaint of shoulder pain due to falling down. The patient presented with various co-morbid conditions, including hypertension, type 2 diabetes, tricuspid valve repair, and aortic valve replacement. She rapidly developed anuria after receiving a single dose of diclofenac over the previous two days of admission. Creatinine and BUN exhibited a significant rise in laboratory tests. During hospitalization, the consumption of NSAIDs was prohibited and losartan and furosemide were discontinued. Moreover, phenacetin was used to relieve pain instead. Luckily, after two days of hospitalization, urine output returned to normal levels. Additionally, creatinine and BUN levels gradually decreased to baseline values. Conclusion: To the best of our knowledge, we described a rare case of diclofenac-induced AKI presenting with anuria, a complete cessation of urine flow, in a patient with no previous kidney complications. This case can be explained by the phenomenon known as “quadruple Whammy,” which involves the concurrent use of NSAIDs, ARBs, and diuretics in the setting of hypovolemia.

Histological study on the effect of açai berry extract in the treatment of fundic mucosal injury in adult male albino rat

Background Gastric injury is a worldwide medical problem. It is caused by many factors. Açai berry is a fruit with many potential medical properties that gained much international interest. Aim To evaluate the possible role of açai berry extract in the treatment of fundic mucosal injury in adult male albino rats. Materials and methods This work was done on 40 adult male albino rats that were divided into; group I (control) (10 rats), group II (10 rats) which were given açai berry extract orally at a dose of 300 mg/kg once per day for 14 days, group III (10 rats) which were given a single dose of diclofenac orally at a dose of 100 mg/kg for induction of gastric injury, and group IV (10 rats) that were given single oral dose of diclofenac then received açai berry extract for 14 days. Specimens from the fundus were processed and stained by hematoxylin and eosin. Results Group III showed exfoliation of surface epithelial cells and gastric glands, infiltration of lamina propria with inflammatory cells, and congestion of the blood vessels. Cytoplasmic vacuolations were detected in different cells. Group IV revealed improved changes that were detected in group III. Conclusion Açai berry extract is effective in the treatment of gastric injury.

Enhancing Awareness of Diclofenac as an Over-the-Counter Analgesic in the Northern Border Region of Saudi Arabia

Introduction: Diclofenac was identified by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency as a high-risk NSAID in terms of its effects on the heart and circulation when administered systemically, i.e. capsules, tablets or injections.
 Objective: To evaluate the knowledge and awareness about over the counter analgesic medication (Diclofenac) among people living in northern border region – Saudi Arabia.
 Methodology: Self-administered cross-sectional study conducted during a period of two months (October and November 2023) on random sample of 430 Saudi people living in the Northern Border Region. The data was analyzed by Microsoft excel program by means of Descriptive statistics.
 Results: Toothache and headache were the most worried pain among participants (32%) and (31%) respectively, majority (72%) of participants buy OTC medication for pain from community pharmacy on the advice of pharmacist. Small percentage (20%) thought that medications containing diclofenac have very few side effects, 76% didn’t know any side effect of diclofenac, 47% didn’t know that diclofenac in high dose has adverse effects on kidney, 71% didn’t know that diclofenac cause gastrointestinal adverse effects. About one fifth of participants (21%) didn’t know the maximum dose of diclofenac when they use it, tablet is the preferred dosage form of diclofenac (27%) followed by granules (16%), dosage of 100 mg is the most frequently used (36%) followed by 50 mg (16%). 
 Conclusion: Saudi people’s knowledge about diclofenac as one member of non-steroidal anti-inflammatory drugs was insufficient. Knowledge about related adverse effects of diclofenac was lacked which exposes to misusage that may carry accidents and severe side effects especially among high-risk population.

α-Tocopherol Ameliorates Redox Equilibrium Disorders and Reduces Inflammatory Response Caused by Diclofenac-Induced Nephrotoxicity in Male Wistar Rats.

Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be nephrotoxic. Vitamin E (α-tocopherol) has been shown to protect against renal toxicity caused by various agents, including NSAIDs. This study aims to evaluate the pathophysiology of renal damage and the nephroprotective effect of vitamin E against DCF-induced renal damage in male Wistar rats. Animal and methods Twenty-four male Wistar rats, divided into six equal groups, were used for the study. Group 1 (control group) was treated with distilled water only, while the other groups received either high or low doses of DCF with or without a fixed dose of vitamin E. Renal function was assessed by measuring serum urea, creatinine, and kidney injury molecule-1 (KIM-1). Oxidative damage and renal antioxidant levels were also assessed. Additionally, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), renal cytokine tumor necrosis factor-α (TNF-α), and histopathological changes were evaluated. Results DCF caused a significant increase in serum urea, creatinine, KIM-1, TNF-α, NF-κB, and malondialdehyde levels compared to the control group. However, in the groups treated with DCF plus vitamin E, a significant reduction (P<0.05) in the levels of pro-inflammatory cytokines and malondialdehyde was observed, along with improvement in renal function indices, superoxide dismutase, catalase, and glutathione peroxidase levels comparable to the control group. The observed renal histopathological changes were consistent with the results of the biochemical parameters between the treated groups and the normal control rats. Conclusion Findings from this investigation suggested that DCF can be nephrotoxic at a certain dose when used for a prolonged duration. Co-administration of vitamin E suppressed the elevated inflammatory cytokines and led to changes in the cell redox-sensitive signaling pathways induced by DCF, with eventual amelioration of the nephrotoxicity.

Encapsulation of Jeruju Leaves Ethanol Extract (Acanthus ilicifolius L.) and It's Antiinflammatory Activities Against Carrageenan-Induced Mice

Jeruju (Acanthus ilicifolius) leaves ethanol extract contains flavonoids that function as an antiinflammatory source. So it is necessary to research to increase the utilization of ethanol extract of Acanthus ilicifolius leaves (A. ilicifolius L.) in encapsulations to increase the stability of antiinflammatory chemical compounds. Concentrated dyestuff extracts are often unstable, so they need to be converted into solid form, and one technique that can be done is encapsulation. Encapsulation aims to protect sensitive components of the material and reduce the degradation of active compounds in the material. The research method begins with preparing samples to be extracted with ethanol solvent, extract phytochemical screening tests, validation determination tests for the analysis method of ethanol extract levels of jeruju leaves, encapsulated formulations, encapsulated physics and chemical properties test and anti-inflammatory tests. In this research, the secondary metabolite compounds contained in the ethanol extract of Jeruju Leaves were flavonoids, phenolics, steroids, and saponins. The determination of the validation of the analysis method of ethanol extract levels of jeruju leaves was obtained by measurement using a UV-vis spectrophotometer and obtained extract levels of 1367,831 mg/g. This research used maltodextrin coating material for encapsulation formulation because it has low viscosity in many ratios, high solubility, has no taste. The freeze-dryer method was used in this study because it produces better drying quality than other drying methods. The physical property test was carried out by analysis using FTIR and SEM while the chemical properties of encapsulation obtained the highest yield proportion of 58.81%, and the highest solubility proportion of 98.76%. Anti-inflammatory testing is carried out using male mice as test animals. Anti-inflammatory testing in mice based on the Rat hind paw oedema method. The average percent inhibition of each dose administered is calculated based on the data results. The high average percent inhibition obtained for Diclofenac Na is 80%. In the research Encapsule 1:12, the 120 mg/KgBW dose had a significant percentage of inhibition of 75.55%, with Na Diclofenac dose of 10 mg/KgBW being 80%.

Determination of Prostaglandins (Carboprost, Cloprostenol, Dinoprost, Dinoprostone, Misoprostol, Sulprostone) by UHPLC-MS/MS in Toxicological Investigations.

Prostaglandins have stimulative influence on the human uterus and therefore were introduced to medical treatment in reproductive healthcare as labor inductors or abortifacients. The UHPLC-ESI-QqQ-MS/MS method was developed for six prostaglandins: carboprost, cloprostenol, dinoprost (PGF2α), dinoprostone (PGE2), misoprostol and sulprostone (substances for pregnancy termination) in pharmaceutical samples and was applied for the toxicological examination of pills containing misoprostol (collected during gynecological examination). There were used two internal standards: misoprostol-d5 and PGF2α-d4. The quantification of analytes was performed in the MRM mode. The linearity of method was in the range from 0.1 to 10 µg/mL, with a coefficient of determination above 0.997 (R2) for each compound. The precision and accuracy values did not exceed ±5.0%. Analysis of the pills revealed the presence of two substances: misoprostol and diclofenac. Misoprostol and diclofenac dose per sample were as follows: 608.8 ng (sample 1), 708.4 ng (sample 2), 618.8 ng (sample 3) and 67.7 mg (sample 1), 65.3 mg (sample 2) 67.3 mg (sample 3), respectively. A simple, precise and reliable method can be applied for routine examinations in terms of clinical and forensic toxicology examinations as well as in quality control of drugs for pharmaceutical purposes (original drugs and counterfeit medications).

Diclofenac and metformin synergistic dose dependent inhibition of hamster fibrosarcoma, rescued with mebendazole

We examined whether combinig diclofenac and metformin in doses equivalent to human doses would synergize their anticancer activity on fibrosarcoma inoculated to hamsters and in vitro. Rescue experiment was performed to examine whether the prosurvival NF-κB stimulation by mebendazole can reverse anticancer effects of the treatment. BHK-21/C13 cell culture was subcutaneously inoculated to Syrian golden hamsters randomly divided into groups (6 animals per group): 1) untreated control; treated daily with 2) diclofenac; 3) metformin; 4) combinations of diclofenac and metformin at various doses; 5) combination of diclofenac, metformin and mebendazole; 6) mebendazole. Dose response curves were made for diclofenac and metformin combination. Tumor growth kinetics, biophysical, pathological, histological and immunohistochemical characteristics of excised tumors and hamster organs as well as biochemical and hematological blood tests were compared among the groups. Single treatments had no anticancer effects. Diclofenac (60 mg/kg/day) exhibited significant (P < 0.05) synergistic inhibitory effect with metformin (500 mg/kg/day) on all tumor growth parameters, without toxicity and influence on biochemical and hematological blood tests. The same results were obtained with double doses of diclofenac and metformin combination. The addition of mebendazole to the diclofenac and metformin combination rescued tumor expansion. Furthermore, diclofenac with metformin demonstrated antiproliferative effects in hamster fibrosarcoma BHK-21/C13, human lung carcinoma A549 (CCL-185), colon carcinoma HT-29 (HTB-38) and cervical carcinoma HeLa (CCL-2) cell cultures, with markedly lower cytotoxicity in the normal fetal lung MRC-5 cells. In conclusion, diclofenac and metformin combination may be recommended for potential use in oncology, due to synergistic anticancer effect in doses achievable in humans.

Evaluation of in vitro antioxidant, anti-inflammatory and antibacterial activities of chloroform leaf extracts of Conocarpus lancifolius Engl

Introduction and Aim: Antibacterial substances are abundant in medicinal herbs, which are used in many extremely effective traditional medical therapies. Conocarpus lancifolius Engl. a plant species, has a wide range of therapeutic uses for the handling of haemophilia, inflammation, illness, eye ailments, fever, diabetes and headache. The study's goal was to assess the antibacterial efficacy, in vitro antioxidant, anti-inflammatory properties of the solvent-based extract of C. lancifolius leaf material. Methodology: The investigation started in March 2023 and C. lancifolius leaves were collected in Tamil Nadu, India. To make the extracts, the maceration technique was employed. The phytochemical constitutions were identified by phytochemical test results. Using the agar diffusion method, the antibacterial capacity of C. lancifolius extracted from leaves was evaluated. Results: At the concentration of 100 microgram/mL level of probability, Gram-positive bacteria including Staphylococcus aureus in addition to Bacillus cereus, respectively (18 and 21 mm) and Gram-negative microorganisms Escherichia coli combined with Klebsiella pneumoniae (23 and 20 mm) were considerably inhibited. Additionally, it has the strongest antifungal activity (20 mm) against Candida albicans. While the ethanol extract of the leaves significantly inhibited both Gram-negative bacteria like Escherichia coli as well as the pneumonia-causing bacteria Klebsiella pneumoniae (22 and 19 mm) and Gram-positive bacteria like Staphylococcus aureus and the yeast Bacillus cereus (18 and 20 mm). Conclusion: When compared to normal ascorbic acid, which had an antioxidant activity of 87.96 percent, C. lncifolius extract with chloroform exhibited a substantial antioxidant activity of 62.96 percent inhibition. When compared to a larger dose of normal diclofenac (84.11 percent), the more potent quantity of C. lncifolius extract with chloroform significantly inhibited inflammation by 75.12 percent under similar circumstances. Because there are biologically active compounds in the herbal preparation, the current investigation found that C. lancifolius may be a good therapeutic candidate.

Fractal-like kinetic modelling for sorption of diclofenac onto graphene oxide/polypyrrole composite: Mechanism analysis and response surface methodology for optimization

Graphene oxide/polypyrrole (GO/PPy) composite material was prepared to explore its utility in the removal of diclofenac from aqueous system. The characterization was achieved using Fourier transform infrared spectroscopy, X-ray powder diffraction analysis, thermogravimetry-differential thermal analyses, scanning electron microscopy coupled with energy dispersive X-ray analysis and transmission electron microscopy analysis. Response surface methodology was exploited to optimize the process variables for the sorption of diclofenac onto GO/PPy. Three variables such as contact time, adsorbent dose and initial concentration of diclofenac were selected for optimization to achieve maximum removal of diclofenac. All experiments were conducted at pH 5. The contact time, adsorbent dose and initial concentration of diclofenac were examined in the ranges of 03–37 min, 13–147 mg/25 mL and 10–110 mg/L, respectively. The optimum values obtained were: contact time: 20 min; GO/PPy dose: 80 mg/25 mL and initial diclofenac concentration: 60 mg/L. The maximum sorption capacity and percent removal of diclofenac were found to be 29.50 mg/g and 98.50 %, respectively. The measured data (at equilibrium) were investigated using different isotherm models and best described by Freundlich model (R2 = 0.9943–0.9952, χ2 = 0.0062–0.0077, APE = 1.45–1.61). The experimental kinetic data were analyzed with the help of fractal-like kinetic models. The kinetic data are best fitted by fractal-like mixed 1,2 order (R2 = 0.9830–0.9886, χ2 = 0.0014–0.0036, APE = 0.6780–1.1059). Adsorption mechanism has been discussed based on kinetic, FTIR and molecular docking studies which indicated the participation of π-π interactions and hydrogen bonding on energetically heterogeneous surface. The adsorption/desorption test demonstrated that GO/PPy had excellent reusability performance up to 15 cycles.

Some Anatomical and Histological effects of Diclofenac Sodium to the Stomach, Kidney and Liver in rats.

Diclofenac sodium (DS) is one of Non-steroidal anti-inflammatory drugs (NSAIDs).It is commonly used to relief pain and treats several disorders like renal diseases, inflammation and fever. This study was designed to show the effects of over dose of diclofenac sodium75ml/kg B.W in 5 days anatomically and histologically to the stomach, kidney and liver. 24 experimental rats were used,femal ages range between 8-10 weeks. The anatomical change include increase weight and grossly change in surface of these organs and mucosa of stomach but histological change in these tissue include damages which can form mucosal erosions in stomach. However, in kidney it causes infraction in the same area of cortex. Moreover, medulla causes congestion, and in liver occur hepatocyte inflammation and increase fibrous tissue.

Evaluation of the role of transcutaneous electrical nerve stimulation for postoperative pain relief in laparoscopic cholecystectomy: a prospective comparative study

BackgroundPostoperative pain after laparoscopic cholecystectomy still remains a fairly common challenge for the anesthesiologist. Commonly used drugs such as NSAIDs and opioids have their own side effects requiring a need to substantially evaluate the use of non-pharmacological methods like TENS as adjuvants to conventional methods of pain control. We studied the effect of transcutaneous electrical nerve stimulation (TENS) on postoperative pain in laparoscopic cholecystectomy. The primary objective was to compare postoperative analgesia between TENS and placebo groups using visual analog scale (VAS). The secondary objectives were to compare the requirement and dosage of rescue analgesia, hemodynamic parameters (blood pressure and heart rate), and incidence of nausea and emesis between placebo and TENS groups. A total of 64 patients of age group 18 years to 60 years of either gender posted for elective laparoscopic cholecystectomy were randomly allocated into two groups using a computer-generated sequence of random numbers: Group P (n= 32): placebo TENS and Group A (n= 32): active TENS. Statistical analysis was performed by the SPSS program for Windows, version 17.0 (SPSS, Chicago, Illinois). Unpaired t test, Mann-Whitney U test, chi-square test, and Fisher’s exact test were used for statistical analysis.ResultsThe two groups were statistically similar in terms of age, gender, and weight. The VAS scores were significantly lower in patients in the active TENS group for up to 2 h after surgery, and the total weighted dose of diclofenac consumed over 8 h in the active TENS group was significantly lower as compared to the placebo TENS group. Patients who received TENS showed significantly less rise in blood pressure and heart rate and remained hemodynamically stable. Total episodes of nausea and emesis though less in the active TENS group were statistically insignificant.ConclusionWe conclude that TENS is an effective adjuvant non-pharmacologic modality for postoperative pain relief after laparoscopic cholecystectomy.

Subchronic effect of different doses ofDiclofenac Sodium on female reproductive system in rats.

NSAIDs are widely utilized drugs in today's world. These medications are well-known for their anti-inflammatory and analgesic properties. The goal of this study was to suggest and explain the subchronic effects of low and high doses of diclofenac on female reproductive system in rats. A total of 24 female rats were divided into 4 groups, six rats in each. The first group was given distilled water as a control, the second and third groups were given diclofenac (1 mg/kg) and(5 mg/kg) respectively. The fourth group was given a combination of diclofenac and mefenamic acid for 35 days. Hormonal, biochemical, and hematological tests were performed. Low dose diclofenac showed no significant change regarding PGE2, LH, progesterone, prolactin, and glutathione, but an increase in FSH, and decrease in estrogen compared to control group were documented. In contrast, high dose diclofenac alone or combined with mefenamic acid showed significant impact on female reproductive system documented by biochemical and histopathological evaluations. At hematological levels diclofenac decrease RBC,HGB, and platelet account but no change in the total WBC were found. Sub-chronic use of DS alone or in combination with mefenamic acid have a deleterious impact on the female reproductive system, oxidative stress and hematological parametersKeywords:NSAIDs, diclofenac sodium, female reproductive toxicity, hematologic.

Systemic Diclofenac Sodium Reduces Postoperative rhBMP-2 Induced Neuroinflammation: A Rodent Model Study.

This is a basic science, animal research study. This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation. rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis. Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups. The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant ( P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively ( P < 0.05). This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2-induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2-induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2-induced inflammation.

Effective bioremediation of clarithromycin and diclofenac in wastewater by microbes and Arundo donax L

Bioremediation of pharmaceuticals has gained large research efforts, but there is still a need to improve the performance of bioremediation systems by selecting effective organisms. In this study, we characterized the capability to remove clarithromycin (CLA) and diclofenac (DCF) by the bacterium Streptomyces rochei, and the fungi Phanerochaete chrysosporium and Trametes versicolor. The macrolide antibiotic CLA and the non-steroid anti-inflammatory DCF were selected because these are two of the most frequently detected drugs in water bodies. Growth and content of the PhCs and a DCF metabolite (MET) by the energy crop Arundo donax L. were also evaluated under hydroponic conditions. The removal rate (RR) by S. rochei increased from 24 to 40% at 10 and 100 µg CLA L−1, respectively, averaged over incubation times. At 144 h, the RR by P. chrysosporium was 84%, while by T. versicolor was 70 and 45% at 10 and 100 CLA µg L−1. The RR by S. rochei did not exceed 30% at 1 mg DCF L−1 and reached 60% at 10 mg DCF L−1, whereas approached 95% and 63% by P. chrysosporium and T. versicolor, respectively, at both doses. Root biomass and length of A. donax were strongly affected at 100 µg CLA L−1. CLA concentration in roots and shoots increased with the increase of the dose and translocation factor (TF) was about 1. DCF severely affected both shoot fresh weight and root length at the highest dose and concentration in roots and shoots increased with the increase of the dose. DCF concentrations were 16–19 times higher in roots than in shoots, and TF was about 0.1. MET was detected only in roots and its proportion over the parent compound decreased with the increase of the DCF dose. This study highlights the potential contribution of A. donax and the tested microbial inoculants for improving the effectiveness of bioremediation systems for CLA and DCF removal.

Anti-inflammatory activity of novel derivatives of pyrazolo [3,4d] pyridazine against digestive system inflammation.

The digestive system is exposed to severe inflammation as a result of taking some medications that have gastrointestinal side effects. Sixty Swiss-albino male mice were randomly distributed into six groups to treat inflammations of the colon, stomach, and small intestine caused by taking high doses of diclofenac (D), with two novel synthesized compounds, pyrazolo [3,4 d] pyridazine derivatives (Co1 and Co2). Myeloperoxidase enzyme activity was determined in the colon and small intestinal tissues. Serum contents of TNF-α, IL-22, IgG, and IgM were determined by ELISA. Histopathological examinations of the colon, small intestinal, and stomach tissues were microscopically analyzed. TNF-α, IL-22, and TNFSF11 gene expression were measured in the colon, intestinal, and spleen using qRT-PCR. Diclofenac caused surface columnar epithelial cell loss, focal necrosis of the gastric mucosa, inflammatory cell infiltration, and congested blood vessels in the stomach, colon, and small intestinal tissues. Co1 component was found to be better than Co2 component in reducing the focal necrosis of gastric mucosa and improving the histological structures of the stomach, colon, and small intestinal tissues. After 14days, the activity of the myeloperoxidase enzyme was increased in group D and decreased in groups DCo1, DCo2, Co1, and Co2. Serum concentrations of TNF-α and IgG were increased, while IL-22 and IGM were reduced in the D, DCo1, and DCo2 groups compared with the Co1 and control groups. TNF-α gene was upregulated in the D group and downregulated in the Co1 group, while the IL-22 gene was downregulated in the D group and upregulated in the Co1 group compared with the control group. The CO1 component may be useful in reducing digestive system inflammation.