Administration Of Diclofenac Sodium Research Articles

Exploring the hepatoprotective effects of silymarin in experimentally induced- diclofenac sodium toxicity in rabbits

The study was aimed to investigate the hepatoprotective effects of varying doses of silymarin against liver damage caused by diclofenac sodium in rabbits. Silymarin, extracted from the Silybum marianum plant, is known for its antioxidant properties and is used to treat liver diseases. The rabbits (n=40) were divided into 4 groups. Group A served as the control (with vehicle solution), group B, as toxin control with diclofenac sodium (50mg/kg intra-peritoneally), group C received both diclofenac sodium and protective dose of silymarin (50mg/kg orally), while group D was administered diclofenac sodium along with higher dose of silymarin (100mg/kg orally). At the study's conclusion, rabbits were humanely euthanized and blood samples were collected for analysis. Enzymes such as Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), direct bilirubin, serum urea, and total bilirubin were measured. The study revealed that higher dose of silymarin (100mg/kg) was more effective in reducing serum enzyme levels compared to lower dose, indicating stronger hepatoprotective effect. This suggests silymarin's potential as the therapeutic agent against liver damage and toxicity induced by substances like diclofenac sodium

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

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

Drug release from Pluronic F68 hydrogels

The evaluation of drug percutaneous absorption plays a pivotal role in assessing the efficacy of dermal/transdermal drug delivery systems. Drug therapies rely on biomedical systems capable of precisely regulating drug dosage, controlling the rate of drug release, and mitigating the common side effects associated with many drug delivery formulations. Pluronics are being broadly used as amphiphilic excipients in many drug delivery systems due to their capacity to create supramolecular assemblies in water, exhibiting significant potential for sustained drug delivery. We herein report on the release kinetics of diclofenac sodium contained in novel biocompatible drug delivery systems consisting of aqueous solutions of Pluronic F68. The latter is tested as a release vehicle for percutaneous administration of diclofenac sodium. Its release from Pluronic F68 nanoassemblies in water was experimentally examined by means of a static Franz-type diffusion cell, equipped with a porous membrane simulating the skin absorption, and supported by rheology. Furthermore, the drug release process was modeled through a mass balance for the diclofenac sodium describing its diffusion in pseudostationary conditions through the porous membrane.

TEST ANTINFLAMMATION CAPSULE COMBINATION OF MORINGA LEAVES (Moringa oleifera L) AND KARUK LEAVES (Piper sarmentosum Roxb. Ex. Hunter) EXTRACT TEST AGAINST MICE (Mus musculus)

Empirically utilized medicinal plants include Moringa leaves (Moringa oleifera L) and Karuk leaves (Piper sarmentosum Roxb. Ex. Hunter). Moringa leaves contain active compounds, such as vitamins, carotenoids, polyphenols, phenolic acids, flavonoids, alkaloids, glucosinolates, isothiocyanates, tannins, saponins, and oxalates. The leaves of karuk contain polyphenols, flavonoids, saponins, and tannins. This study aimed to assess the anti-inflammatory activity of combination capsules of Moringa and Karuk leaf extracts in mice (Mus musculus). Anti-inflammatory agents are drugs that can suppress or reduce inflammation. The aim of the experimental method used in this study was to determine the optimal concentration for anti-inflammatory activity. Carrageenan as an inflammatory mediator in mouse paws. The anti-inflammatory test involved five groups of animals, each consisting of five mice. The negative control group received Na-CMC, the positive control group was administered diclofenac sodium, and the test samples involved a combination capsule of Moringa and Karuk leaf extract at doses of 350, 700, and 1,050 mg. Measurements were performed every hour for 6 hours after carrageenan induction. Data analysis employed the One-way ANOVA method to ascertain whether variations in the dose of the combination capsule of Moringa and Karuk leaf extracts affected anti-inflammatory activity in mice. The results indicate that the greatest inflammation inhibition occurs with the 1,050 mg dose, resulting in 23% inhibition, followed by 22% at 700 mg and 13% at 350 mg. Statistical analysis yielded a p-value of 0.048, which was less than 0.05. This suggests a significant difference in the anti-inflammatory activity among the test groups ...

Novel gastroprotective activity of basella alba mucilage-based hydrogel beads on diclofenac sodium induced gastric ulcer

Natural polysaccharides are emerging gastro-protective agents that need extensive characterization and subsequent commercialization. Diclofenac sodium, a non-steroidal anti-inflammatory drug, is generally used as a model drug to induce gastric ulcers experimentally. Therefore, in the present study, Basella alba mucilage is modified to form hydrogel beads, and its gastro-protective potential is judged by incorporating Diclofenac sodium in it and administered orally to Swiss albino rats at an equivalent weight of 50mg Diclofenac sodium/ kg bw for ten days. The results were compared with the rats administered Diclofenac sodium (50 mg/kg bw) and with the group of rats administered Diclofenac sodium (50mg/kg bw) and Pantoprazole (10mg/kg bw). Another group of rats were administered blank hydrogel beads, and another group served as control. The gastro-protective property was evaluated from the gastric secretory parameters, ulcer index, biochemical tests, and histopathology studies. The administration of Basella alba mucilage-based hydrogel beads in rats decreased the ulcer index, total and free acidity, lipid peroxidation, hydrogen peroxide level, and myeloperoxidase activity. It elevated the level of enzymic antioxidants and increased gastric juice's pH significantly compared to the Diclofenac-treated rats. All the evaluated parameters showed similar results for the rats treated with Diclofenac sodium-loaded Basella alba mucilage beads and those treated with Diclofenac sodium and Pantoprazole, with no significant differences. The histopathology analysis also supports the gastro-protective property of the beads. Thus, Basella alba mucilage-based hydrogel beads can be a promising gastro-protective agent against Diclofenac sodium-induced gastric ulcers.

Fabrication and In vitro Evaluation of Carbopol/Polyvinyl Alcohol-based pH-sensitive Hydrogels for Controlled Drug Delivery.

Diclofenac sodium has a short half-life (about 1.5 hours), requiring repeated administration, and as a result, serious complications, such as GI bleeding, peptic ulcer, and kidney and liver dysfunction, are generated. Hence, a sustained/controlled drug delivery system is needed to overcome the complications caused by the administration of diclofenac sodium. This study aimed to fabricate and evaluate carbopol/polyvinyl alcohol-based pH-sensitive hydrogels for controlled drug delivery. pH-sensitive carbopol/polyvinyl alcohol graft-poly(acrylic acid) hydrogels (Cp/PVA-g-PAa hydrogels) were developed for the controlled delivery of diclofenac sodium. The combination of carbopol/polyvinyl alcohol, acrylic acid, and ethylene glycol dimethacrylate was used as polymer, monomer, and cross-linker, respectively. The effects of the formulation's composition on porosity, swelling index, and release pattern of diclofenac sodium from the developed hydrogels were investigated. An increase in porosity and swelling was observed with the increasing amounts of carbopol and acrylic acid, whereas polyvinyl alcohol showed the opposite effect. Due to the formation of a highly viscous system, the drug release decreased with the increasing concentrations of carbopol and polyvinyl alcohol while increased with increasing acrylic acid concentration. The pH-responsive properties of the fabricated hydrogels were demonstrated by dynamic swelling and drug release studies at three different pH values. Higher dynamic swelling and diclofenac sodium (model drug) release were found at high pH values compared to low pH values, i.e., pH 7.4 > 4.6 > 1.2, respectively. Cytotoxicity studies reported no toxic effect of the prepared hydrogels, thus indicating that the prepared hydrogels are safe to be used on clinical basis. The prepared carbopol/polyvinyl alcohol crosslinked hydrogel can be used as a promising carrier for the controlled release of drugs.

Haematological Changes Following Intramuscular and Per- Rectal Diclofenac Sodium Administration in Dogs undergoing Orchiectomy

A total of 30 Nigerian indigenous male dogs aged 1-2 years (1.65±0.47) and 11-15kg (13.4±1.27) body weight were used for the study. They were randomly allocated into 6 groups of 5 dogs each. Groups A1, B1 and C1 for intramuscular at 2mg/kg, 3mg/kg and 4mg/kg respectively and Groups A2, B2 and C2 for per-rectal at 2mg//kg, 3mg/kg and 4mg/kg. Haematological values of Packed cell volume (PCV), haemoglobin (Hb), Red blood cell (RBC), White blood cell (WBC) and Differential leucocyte counts (DLC) of Lymphocyte (LYM), Neutrophils (NEU), Monocyte (MON) and Eosinophils (EOS) were determined. Statistical Package for Social Sciences Software Version 22.0 (SPSS Inc. Chicago. Illinois). General Linear Model (GLM) using repeated measures Analysis of Variance (RM-ANOVA), to compare the mean of different groups at a 95% confidence interval and a 5% level of significance was used. The PCV, Hb and Rbc values of the dogs castrated were within normal range when compared with specie corresponding values. The PCV value was lowest 38.6±1.9 at 2nd hour 2mg/kg for per rectum and highest of 44.1±1.9 at the 9th hour for per rectum at 4mg/kg dose. The Hb value was lowest at 12.9±0.5 at 1st hour for per rectum at 4mg/kg dose and the highest of 15.3±0.8 at 0 hour for intramuscular at 2mg/kg. The Rbc value was lowest at 4.0±1.5 at 4th hour, 2mg/kg for per rectum and the highest of 6.6±0.3 at 7th hour, 2mg/kg. The Total leucocyte count (TLC) values of WBC and DLC also recorded significant differences. There was significant difference (P&lt;0.05) between routes but values remain within normal range of values. This finding shows that the use of Diclofenac as a short term analgesic caused no significant changes on the haematocrit values of dogs when used after castration. This finding has also indicated that short-term use of diclofenac through the per rectum route may be safe and had no deleterious effect on haematological value of Nigerian indigenous male dogs

The effect of tilmicosin and diclofenac sodium combination on cardiac biomarkers in sheep.

The aim of this study was to investigate the cardiotoxic effect of the combination of tilmicosin and diclofenac sodium in sheep. Thirty-two sheep were used and were randomly divided into four equal groups as tilmicosin (T), diclofenac sodium (D), tilmicosin+diclofenac sodium (TD) and control (C) group. Group T received a single dose of tilmicosin, Group D was administered diclofenac sodium once a day for 3 days, and group TD was administered diclofenac and tilmicosin at the same doses as group T and D. Group C received NaCl in a similar way. The blood samples were taken before dosing and at 4th, 8th, 24th and 72nd hour post-dosing for measurement of cardiac markers such as H-FABP, cTn-I, CK-MB. H-FABP level of group TD was found to be significantly (p⟨0.05) higher than of group C at the 8th, 24th and 72nd hour and group D and T at the 72nd hour. cTn-I and CK-MB levels of group TD were found significantly (p⟨0.05) higher compared with other groups. In conclusion, the combined use of tilmicosin and diclofenac in sheep causes an increase in cardiac biomarkers and it can be stated that this combination of drugs may cause cardiac damage.

Chondroprotective Effects of Grapefruit (Citrus paradisi Macfad.) Juice in a Complete Freund’s Adjuvant Rat Model of Knee Osteoarthritis

Osteoarthritis (OA) is a common disorder that can affect any joint in the human body. This study aimed to examine the anti-arthritic properties of high and low doses of grapefruit juice (GFJ), as grapefruit appears to contain anti-inflammatory biochemicals. Forty male Sprague-Dawley rats weighing 170-180 g were divided into five groups. These groups comprised the untreated control group and osteoarthritic (Osteo) rats administered intra-articular injections of Freund's complete adjuvant (CFA; 0.5 mL; 1 mg/mL) as follows: OA rats administered low doses of GFJ (Osteo+GFJ (low); 5 mL/kg body weight (BW)); OA rats administered high doses of GFJ (Osteo+GFJ (high); 27 mL/kg BW); and OA rats administered diclofenac sodium (Osteo+Diclo) as a reference drug. Injections of CFA induced OA, as indicated by a significant increase in the serum levels of the inflammatory biomarkers C-reactive protein (CRP), interleukin-1β (IL-1β), and (prostaglandin (PGE2), as well as matrix metalloproteinases (MMP-1) and cathepsin K. The synovial levels of glycosaminoglycans (GAGs), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6) also increased, with a concomitant reduction in osteocalcin levels. The administration of either high or low doses of GFJ reduced CRP, IL-1β, PGE2, MMP-1, cathepsin K, and osteocalcin while increasing the synovial levels of GAGs, TNF-α, and IL-6, slowing cartilage degradation and boosting joint function. The results showed comparable histopathological and biochemical responses. A comparison of the treatments showed that high-dose GFJ had a greater chondroprotective effect than low-dose GFJ.

Mandarin peel ethanolic extract attenuates diclofenac sodium induced hepatorenal toxicity in rats by mitigating oxidative stress and inflammation

Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute approximately one-third of the global pharmaceutical market and are the first drugs of choice when treating fever and pain. Furthermore, among NSAIDs, the use of diclofenac sodium (DS) is preferred as it is a strong inhibitor of cyclooxygenase enzyme. However, despite its strong efficacy, DS is known for its potential to cause hepatorenal damage. Currently, to mitigate the adverse effects of certain drugs, medically effective agricultural products are often preferred as they are inexpensive, effective and safe. One such agricultural product—mandarin—is noteworthy for its high phenolic contents. The purpose of the present study was to assess the efficacy of mandarin peel ethanolic extract (MPEE) in protecting against hepatorenal damage induced by DS. Four groups (six/group) of adult male albino rats received oral administration of physiological saline (control group), DS (10 mg/kg body weight), MPEE (200 mg/kg body weight), and DS + MPEE for 7 days. Rats in the DS group showed increased serum levels of ALT, AST, ALP, BUN, CRE, and UA. Furthermore, the hepatic and renal tissue levels of MDA, TNF-α and IL-1β increased, whereas those of GSH, SOD, GP-x and IL-10 decreased (p < 0.05). Investigation of MPEE in terms of its effects on biochemical, oxidative and inflammatory parameters, it exerted protective and healing effects. Therefore, MPEE can be used to ameliorate DS-induced hepatorenal damage.

Dissolvable Carboxymethylcellulose Microneedles for Noninvasive and Rapid Administration of Diclofenac Sodium.

The aim of this study is to prepare dissolvable biopolymeric microneedle (MN) patches composed solely of sodium carboxymethylcellulose (CMC), a water-soluble cellulose derivative with good film-forming ability, by micromolding technology for the transdermal delivery of diclofenac sodium salt (DCF). The MNs with ≈456µm in height displayed adequate morphology, thermal stability up to 200 °C, and the required mechanical strength for skin insertion (>0.15 N needle-1 ). Experiments in ex vivo abdominal human skin demonstrate the insertion capability of the CMC_DCF MNs up to 401µm in depth. The dissolution of the patches in saline buffer results in a maximum cumulative release of 98% of diclofenac after 40min, and insertion in a skin simulant reveals that all MNs completely dissolve within 10min. Moreover, the MN patches are noncytotoxic toward human keratinocytes. These results suggest that the MN patches produced with CMC are promising biopolymeric systems for the rapid administration of DCF in a minimally invasive manner.

Synergistic Effect of Diclofenac Sodium and Sulfamethoxazole in Pure form, Microparticle Formulation and in Carbopol Incorporated Gel Containing Microparticle Formulation

As infectious diseases are connected with pain and infections, treating pain and infection should be prioritized. Patients suffering from bacterial infection may need diclofenac sodium (DS) during the regular use of sulfamethoxazole (SM) treatment. So, simultaneous or following administration of DS and SM may be needed. The goal of this study was to prepare six microparticle formulations (MF-1-MF-6) made up of Polyethylene glycol-6000 (PEG-6000) with and without chitosan and that was loaded with two drugs (DS and SM) by cold/hot (melt) dispersion method. The formulated microparticle was then mixed with carbopol gel (0.75 and 1.00% w/v) and evaluated. The percentage yield for all the formulated microparticles was found to be between 94.13% and 97.18%. The drug content for both DS and SM is within the prescribed limits. The microparticle size studies revealed that microparticles prepared without chitosan had smaller particles than those prepared with chitosan. The in vitro drug release results illustrate that the release of DS and SM from prepared microparticles is increased for the preparation containing chitosan compared to without chitosan preparation. When compared to microparticles alone, the microparticles in gel formulations demonstrated slow drug release. Based on the obtained results of the work, it may be concluded that chitosan increases particle size, and subsequently, drugs are released more rapidly. The research also suggests that DS and SM produce synergistic drug release when administrated together in pure, microparticle, and gel form.

Nicolau’s syndrome following intramuscular administration of Diclofenac sodium

Nicolau’s syndrome, also known as embolia cutis medicamentosa or livedo-like dermatitis, is an uncommon rare cutaneous adverse reaction occurring at the site of intramuscular, intra-articular, or rarely subcutaneous injection of particular drugs, leading to necrosis of skin and underlying tissues. We, hereby, report two fatal cases of this syndrome after taking intramuscular injection of diclofenac sodium.

Histological and Immunohistochemical Study on the Effect of Prenatal Administration of Diclofenac Sodium on Maternal and Neonatal Organs in albino rat

Histological and Immunohistochemical Study on the Effect of Prenatal Administration of Diclofenac Sodium on Maternal and Neonatal Organs in albino rat

An Experimental Study of the Cryopreserved Placenta Extract Effect On the Sodium Diclofenac Anti-Inflammatory Activity

Background. As a means of correcting the ulcerogenic effect of nonsteroidal anti-inflammatory drugs, our attention was attracted by a cryopreserved extract of the human placenta, which has a multivector spectrum of biological activity. To date, there is no information about its effect on the specific activity of this class of medicines (anti-inflammatory, analgesic, etc.) in published sources. Objective. We are aimed to characterize the effect of cryopreserved placenta extract on the anti-inflammatory activity of diclofenac sodium when administered separately in a model of acute exudative inflammation. Methods. Experimental studies in vivo were conducted on 28 nonlinear male laboratory rats. The model of acute exudative inflammation was reproduced by subplantar injection of 0.1 ml of 1.0% aqueous solution of λ-karagenin into the right hind limb of rats. Cryopreserved placenta extract was administered intramuscularly at a dose of 0.16 ml/kg 60 minutes before diclofenac sodium (8 mg/kg). Results. Preventive administration of diclofenac sodium caused an antiexudative effect as early as 30 minutes after administration of λ-karagenin – its anti-inflammatory activity was 11.0%, which is 4.6 times higher than similar indicators at the same time in rats injected with placental cryoextract. At 60 minutes of observation, diclofenac sodium was comparable in anti-inflammatory activity with cryopreserved placenta extract: 28.6% and 22.2%, respectively, but at 120 and 180 minutes, diclofenac sodium exceeded the studied cryoextract in antiphlogistic effect by 1.6 times in both periods of observation. The anti-inflammatory effect of the combined separate administration of placenta cryoextract and diclofenac sodium before λ-karagenin for 30 and 60 minutes was 12.7% and 32.3%, respectively, which is comparable with analogous indicators against the background of diclofenac sodium monotherapy. However, at 120 minutes of observation, the group of combined use of placenta cryoextract and diclofenac sodium showed the greatest anti-inflammatory effect among rats of all the studied groups – 52.6%, which was 2.2 times higher than the indicators of the placenta cryoextract monotherapy group and 1.4 times lower than the indicators of the rats of the diclofenac sodium monotherapy group. Conclusions. 4 hours after administration, placental cryoextract had a suppressive effect on kinins like diclofenac sodium, and in the prostaglandin period of caragenin-induced inflammation against the background of combined use of the studied cryoextract and diclofenac sodium, the anti-inflammatory activity was 46.4 %. This suggests a suppressive effect on the production of prostaglandins as a possible mechanism of anti-exudative action of cryopreserved placenta extract.

A Novel Carbon Dots/Thermo-Sensitive In Situ Gel for a Composite Ocular Drug Delivery System: Characterization, Ex-Vivo Imaging, and In Vivo Evaluation.

We developed a potential composite ocular drug delivery system for the topical administration of diclofenac sodium (DS). The novel carbon dot CDC-HP was synthesized by the pyrolysis of hyaluronic acid and carboxymethyl chitosan through a one-step hydrothermal method and then embedded in a thermosensitive in situ gel of poloxamer 407 and poloxamer 188 through swelling loading. The physicochemical characteristics of these carbon dots were investigated. The results of the in vitro release test showed that this composite ocular drug delivery system (DS-CDC-HP-Gel) exhibited sustained release for 12 h. The study of the ex vivo fluorescence distribution in ocular tissues showed that it could be used for bioimaging and tracing in ocular tissues and prolong precorneal retention. Elimination profiles in tears corresponded to the study of ex vivo fluorescence imaging. The area under the curve of DS in the aqueous humor in the DS-CDC-HP-Gel group was 3.45-fold that in the DS eye drops group, indicating a longer precorneal retention time. DS-CDC-HP with a positive charge and combined with a thermosensitive in situ gel might strengthen adherence to the corneal surface and prolong the ocular surface retention time to improve the bioavailability. This composite ocular delivery system possesses potential applications in ocular imaging and drug delivery.

EFFECT OF CRYOPRESERVED PLACENTA EXTRACT ON SOME BIOCHEMICAL INDICES OF THERAPEUTIC EFFICIENCY AND TOXICITY OF DICLOFENAC SODIUM IN ADJUVANT-INDUCED EXPERIMENTAL ARTHRITIS

Non-steroidal anti-inflammatory drugs are among the top requested ones in the clinic of internal medicine. However, these drugs are associated with a wide range of adverse reactions involving a number of organs and systems, in particular the gastrointestinal tract, cardiovascular system and kidneys. The aim of the study is to characterize the effect of the combined use of cryopreserved placenta extract and diclofenac sodium on the prooxidant-oxidative system, the activity of inflammatory, destructive and cytolytic processes, as well as protein and lipid metabolism in rats with experimental rheumatoid arthritis. Results. The administration of diclofenac sodium and cryopreserved placenta extract to rats with adjuvant arthritis normalized the level of active products of thiobarbituric acid and hence was indicative of the neutralization of an arthritis-induced oxidative stress. A statistically significant (p=0.01) increase of in a superoxide dismutase activity (by 30.6% relative as compared with rats of the control group) has also been established. An increase in the anti-inflammatory properties of diclofenac sodium in the combined use of diclofenac sodium with a cryopreserved placenta extract has been found out. The level of C-reactive protein decreased (p&lt;0.001) by 61.1% as compared with the untreated rats, and the level of seromucoid has been significantly (p&lt;0.01) decreased by 17.1% as compared with the rats of the monotherapy group treated with the studied NSAIDs. It was shown that alanine aminotransferase and aspartate levels were significantly lower (by 38.9%, p&lt;0.01 and by 37.9%, p&lt;0.01, respectively) as compared with those of the animals that had been administrated with diclofenac sodium. Their indices were by 16.7% (p=0.02) and 17.2% (p&lt;0.001) lower than the indices of the control group rats with untreated adjuvant arthritis. The established changes of aminotransferases levels indicate the ability of a cryopreserved placenta extract to level not only an arthritis-induced cytolytic syndrome, but also a diclofenac-induced one. The combined use of cryopreserved placenta extract and diclofenac sodium was accompanied by the normalization of the total lipids level and phospholipids in the blood serum of rats against the background of experimental rheumatoid arthritis. Thus, the content of phospholipids in the lipid pool statistically significantly (p=0.02) increased by 22.6% as compared with the indices of the animals with adjuvant arthritis without treatment. Conclusion. The study showed that the combined use of diclofenac sodium and cryopreserved placenta extract leads to the restoration of the balance of the prooxidant-antioxidant system that is more pronounced than monotherapy with diclofenac sodium. A decrease in the activity of inflammatory, destructive and cytolytic processes, as well as the restoration of lipid metabolism in the rats with experimental rheumatoid arthritis, has also been observed.

Protective effect of three developed gel formulations: Chitosan, Chitosan with Taurine and Chitosan with Dexpanthenol, on the acute overdose of Diclofenac sodium in preclinical studies

Objectives: To investigate the tissue-protective effects of three gel formulations (chitosan, chitosan with taurine or chitosan with dexpanthenol) as active substances against an acute overdose of diclofenac sodium. Methods: White outbred conventional male rats were allocated to five experimental groups: the first is an intact group that did not receive any drug, the second group is a control group that received 50mg/kg of diclofenac sodium once orally, the third, fourth and fifth groups are an experimental group that received our studied drugs at a dose of 0.16ml/100mg b.w. once orally 1 hr. before diclofenac sodium, the third group received chitosan-based gel 1%, the fourth group received chitosan-based gel 1% with 4% taurine and the fifth group chitosan-based gel 1% with 0.43% dexpanthenol. Blood samples were taken for biochemical, hematological and blood coagulation system tests on day 7th after administration of diclofenac sodium. Results: An acute overdose of diclofenac sodium caused marked extensive tissue necrosis in the liver, bleeding in the gastrointestinal tract and inflammatory process, these marks were evidenced by different changes in the test of the blood samples. Significantly 73.6% of the blood indicators were improved by the administration of chitosan-based gel 1% with 0.43% dexpanthenol, while 57.8% were improved by chitosan-based gel 1% with 4% taurine and 68.4% by chitosan-based gel 1%. Conclusion: Chitosan-based gel 1% with dexpanthenol 0.43% can help in mitigating hepatic injury, gastrointestinal bleeding, and systemic and local intestinal inflammation caused by an acute overdose of diclofenac sodium.

Effects of Mast Cells Induced by NSAIDs Impair Intestinal Epithelial Barrier Function In Vivo and In Vitro

To explore the correlation between altered expression of mast cells and PAR-2 and impaired mucosal barrier in NSAIDs enteropathy through animal and cell experiments, and to elucidate the role of mast cells and PAR-2 in the pathogenesis of NSAIDs enteropathy and the regulatory mechanism of the tight junction of intestinal epithelium. Animal experiments: the NSAIDs-related small intestine injury model was established by intragastric administration of diclofenac sodium, and mast cells were detected by toluidine blue staining. Cell experiments: Intestinal epithelial cell line (IEC-6) was applied with diclofenac sodium and its activity was detected by CCK-8.IEC-6 and RBL-2H3 were co-cultured to evaluate the permeability of intestinal epithelial cells by detecting the concentration of potassium ion and LDH. The expressions of tight junction proteins (zo-1, claudin-1, occludin), cytoskeletal components (actin, tubulin, keratin) and par-2 were analyzed by Western Blot. In animal experiments, the number of mast cells was significantly increased after 24 h of action of diclofenac sodium. In cell experiments, the survival rate of IEC-6 cells decreased significantly when the concentration of diclofenac sodium is more than 50 μg/mL; after 24 h of co-culture, the potassium and LDH concentration in the co-culture group were significantly higher, and the expression of ZO-1, claudin-1, occludin, tubulin, and keratin was decreased. Mast cells activate PAR-2 in intestinal epithelial cells, downregulate the related proteins of cell tight junctions and cytoskeletal proteins, and increase the permeability of intestinal epithelial cells.

Cinnamon Aqueous Extract Attenuates Diclofenac Sodium and Oxytetracycline Mediated Hepato-Renal Toxicity and Modulates Oxidative Stress, Cell Apoptosis, and Inflammation in Male Albino Rats.

Among commonly consumed anti-inflammatory and antimicrobial drugs are diclofenac sodium (DFS) and oxytetracycline (OTC), especially in developing countries because they are highly effective and cheap. However, the concomitant administration of anti-inflammatory drugs with antibiotics may exaggerate massive toxic effects on many organs. Cinnamon (Cinnamomum zeylanicum, Cin) is considered one of the most broadly utilized plants with various antioxidant and anti-inflammatory actions. This study aimed to evaluate the possible protective effects of cinnamon aqueous extract (Cin) against DFS and OTC hepato-renal toxicity. Eight groups (8/group) of adult male albino rats were treated orally for 15 days with physiological saline (control), Cin aqueous extract (300 mg/kg b.w.), OTC (200 mg/kg b.w.), single dose of DFS at the 14th day (100 mg/kg b.w.), DFS + OTC, Cin + DFS, Cin + OTC, and Cin + DFS + OTC. The administration of DFS and/or OTC significantly increased (p < 0.05) the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, creatinine, and uric acid. Serum levels of pro-inflammatory cytokines, as well as hepatic and renal malondialdehyde and nitric oxide metabolites, were also raised following DFS and OTC administration. Meanwhile, the activities of reduced glutathione, superoxide dismutase, and catalase in liver and kidney were significantly suppressed in DFS, OTC, and DFS + OTC treated rats. Moreover, hepatic and renal tissue sections from these rats exhibited overexpression of caspase-3 and cyclooxygenase-II on immunohistochemical investigation. The administration of Cin aqueous extract ameliorated the aforementioned deteriorations caused by DFS, OTC, and their combination. Conclusively, Cin is a promising protective plant extract capable of attenuating the oxidative damage, apoptosis, and inflammation induced by DFS and OTC either alone or combined, on hepatic and renal tissues.