Diclofenac In Rats Research Articles

Comparative clinicopathological studies on the anti-inflammatory effect of ashwagandha and diclofenac in rats

Comparative clinicopathological studies on the anti-inflammatory effect of ashwagandha and diclofenac in rats

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

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

Comparative Clinicopathological studies on the anti-inflammatory effect of Ashwagandha and Diclofenac in rats

Comparative Clinicopathological studies on the anti-inflammatory effect of Ashwagandha and Diclofenac in rats

Analgesic effect of externally applied and/or intraperitoneal hemantane and diclofenac in rats with postoperative pain

Analgesic effect of externally applied and/or intraperitoneal hemantane and diclofenac in rats with postoperative pain

Diclofenac and eugenol hybrid with enhanced anti-inflammatory activity through activating HO-1 and inhibiting NF-κB pathway in vitro and in vivo

A series of diclofenac hybrid molecules were synthesized and evaluated for their NO-inhibitory ability in LPS-induced RAW 264.7 macrophage cells. Among them, compound 1 showed the highest NO-inhibitory ability (approximately 66%) and no significant cytotoxicity. Compound 1 exhibited superior NF-κB-inhibitory ability compared to diclofenac through the activation of Nrf2/HO-1 signaling pathway in RAW 264.7. 20 mg/kg compound 1 resulted in remarkable colitis improvement in dextran sulfate sodium (DSS)-induced mice model by up-regulating HO-1 and down-regulating phosphorylation level of NF-κB p65. Moreover, 50 mg/kg dose of compound 1 showed a lower ulcerogenic potential compared to diclofenac in rats. The diclofenac-eugenol hybrid (compound 1) may serve as a novel anti-inflammatory agent based on its role in inhibiting the NF-κB signaling pathway and activating HO-1 expression with no toxicity in vitro and in vivo.

Ameliorative Effect of Cannabidiol against Gastric Ulcer Induced by Diclofenac in Rats

Purpose: The aim of his study is to examine the effect of using cannabidiol upon gastric ulcer induced by diclofenac in rats. Method: The experiment was conducted on four groups, with normal rats serving as a control in group one. A single oral dose of diclofenac was administered to Group 2 rats in order to induce a stomach ulcer. The rats in the third group were given a single oral dosage of diclofenac sodium, followed by a 5-day therapy with cannabidiol, which began three days before the diclofenac administration. Drug control on cannabidiol-treated rats in the final group (Group 4). Results: The investigation showed that when cannabidiol was administered, the levels of acidity from diclofenac use decreased, significantly. Conclusion: The investigation resulted in a decrease in overall acidity levels among the rats treated with diclofenac, indicating that cannabidiol was effective in treating the condition.

Effect of rutin on pharmacokinetic modulation of diclofenac in rats

Diclofenac is an extensively used nonsteroidal anti-inflammatory drug, but gastrointestinal liabilities and cardiovascular complications take the shine away from such a widely prescribed drug. On the other hand, rutin, a dietary bioflavonoid, has quite a few pharmacological attributes to improve the efficacy and reduce the dose-related toxicities of diclofenac through the intended food-drug/herb-drug interaction. The aim of the present research work was to investigate the role of rutin on pharmacokinetic modulation and the consequent efficacy of diclofenac. At first, pharmacodynamics and pharmacokinetics of diclofenac as alone and in the presence of rutin were investigated orally in a rat model. Then, mechanistic studies were performed to explain the effect of rutin on improvement in oral exposure as well as the efficacy of diclofenac using a battery of in-vitro/in-situ/in-vivo studies. Results displayed that rutin enhanced efficacy as well as oral bioavailability of diclofenac in rats. A marked increase in permeability of diclofenac by rutin was displayed that is linked to inhibition of Breast Cancer Resistance Protein (BCRP) transporters. There was no significant effect of rutin on the modulation of intestinal transit, CYP2C9 inhibition in human liver microsomes, and CYP2C9/CYP2C11 expression in rat liver tissues to boost the oral exposure of diclofenac. Rutin is found to be an inhibitor for BCRP transporters and can act as an oral bioavailability enhancer for a drug like diclofenac.

Effect of probiotic supplementation on oxidative stress markers in rats with diclofenac-induced hepatotoxicity.

In this study, we have investigated the effect of an antioxidant probiotic pretreatment toward an overdose of diclofenac in rats (100mg/kgbw). Rats were treated daily with the probiotic Streptococcus salivarius St.sa (109CFU) during seven successive days and then received a single treatment with diclofenac overdose in distilled water. Liver transaminases (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), histology, glutathione (GSH) and malondialdehyde (MDA) level were investigated. In addition, both antioxidant enzyme activity and its mRNA gene expression were studied to evaluate diclofenac hepatotoxicity. The results indicated that probiotic pretreatment reduced diclofenac-induced hepatotoxicity through enhancement of the studied hepatic markers and regulation of antioxidant enzyme expression and activity. These findings indicate that the probiotic pretreatment protects rat liver against the oxidative stress induced by diclofenac overdose.

Evaluation of the modulatory effects of Piper guineense leaves and seeds on egg albumin-induced inflammation in experimental rat models

Ethnopharmacological relevanceInflammation processes are implicated in many degenerative diseases. Piper guineense, a West African spice belonging to the Piperaceae family has been reported to contain anti-inflammatory agents. Aim of studyThis study determined the modulatory effects of methanolic extracts of Piper guineense leaves and seeds on egg albumin-induced inflammation in rats.Study design and methods: Inflammation in the hind paw was induced by injecting 0.1ml egg albumin subcutaneously. Treatments including diclofenac were given orally. Rectal temperature and paw size were monitored hourly for the first 3 h’ post-induction of inflammation and then at the 6th and 24th hour. Serum levels of CRP, MDA, LDH and GGT activities were determined at these hours. ResultsResults showed that egg albumin-induced inflammation caused a significant (p < 0.05) increase in paw size and rectal temperature. It further showed that treatment with the leaves and seed extracts reversed the effect of inflammation on serum levels of CRP and MDA, and on LDH and GGT activities similar to diclofenac in rats. ConclusionExtracts of the Piper guineense seed and leaves have potentials of being used as an anti-inflammatory agent but further studies need to be done to determine their toxicity and effects on immunological markers of inflammation.

Kolaviron Diminishes Diclofenac-Induced Liver and Kidney Toxicity in Wistar Rats Via Suppressing Inflammatory Events, Upregulating Antioxidant Defenses, and Improving Hematological Indices.

Diclofenac (DF) is widely used in the treatment of pain and fever. Despite it therapeutic benefits, it triggered hepatorenal injury. Thus, the present study investigated the protective roles of kolaviron (KV) against DF-induced hepatic and renal toxicity in rats. The rats were allotted into groups: control group received propylene glycol and treatment groups received DF, which induced hepatorenal toxicity in rats and different doses of KV that prevented systemic toxicity of DF in rats. Twenty-four hours after the last treatment, all the rats were killed. Pro-inflammatory levels, markers of liver and kidney functions, oxidative stress, hematological indices, and histopathological alterations were evaluated. Diclofenac caused significant increase in the plasma levels of creatinine and urea and activities of liver enzymes, including bilirubin level, pro-inflammatory markers, and plasma prostaglandin E2 (PGE2). It also caused significant alteration in renal and hepatic PGE2, antioxidants, lipid peroxidation (malondialdehyde), and hematological indices. These toxic effects were confirmed by histological studies and levels of inflammatory infiltration (myeloperoxidase). However, KV significantly prevented or reduced the adverse effects of DF in the plasma, liver, and kidney of the rats pretreated with KV before DF administration. This study showed the efficacy of KV as hepatic and renal protector in DF-induced hepatorenal toxicity through reduction of oxidative stress and suppression of inflammation.

Small Intestine Protection of Mica Against Non-Steroidal Anti-Inflammatory Drugs-Injury Through ERK1/2 Signal Pathway in Rats.

Objective: The impact of non-steroidal anti-inflammatory drugs (NSAIDs) to damage the small intestine has been well known. Mica, one kind of natural clay, has been widely marketed in China for the treatment of gastric diseases. However, the role and mechanism of mica in small intestinal injure is still unknown. The study was designed to declare the effects of mica on intestinal injury induced by diclofenac in rats. Methods: Rats were randomly divided into control, model, PAR-2 agonist group (SLIGRL-NH2group), control peptide group (LRGILS-NH2 group), and ERK blocker group (eight mice per group). Morphological changes of mucous membrane of small intestine were observed, and the expression of tryptase, PAR-2, and p-ERK1/2 was measured by immunohistochemistry and western blot. PAR-2 mRNA was tested by qRT-PCR. Rats were also randomly divided into control, model, and mica group (eight mice per group). Morphological changes of mucous membrane were observed. The expression of tryptase, PAR-2, and p-ERK1/2 was measured by immunohistochemistry. Results: The expression of trypsin, PAR-2, and p-ERK1/2 was increased in model group compared with control. The expression of PAR-2 and p-ERK1/2 was increased in SLIGRL-NH2 group compared with model, but not LRGILS-NH2 group. The expression of PAR-2 was down-regulated in ERK blocker group compared with SLIGRL-NH2 group. Macroscopically visible lesions of mucous membrane were positively correlated with the expression of PAR-2 and p-ERK1/2. Furthermore, we also found that mica could inhibit small intestinal injure, as evidenced by the improvement of macroscopic damage. Tryptase, PAR-2, and p-ERK1/2 expression was down-regulated in mica group compared with model group. Conclusion: Mica inhibit small intestinal injury induced by NSAIDs via ERK signaling pathway.

Nephroprotective effect of silymarin against diclofenac induced renal damage and oxidative stress in male rats

Introduction: Diclofenac (DIC), a phenylacetic acid compound which belongs to nonsteroidal anti-inflammatory drugs (NSAIDs), is generally used for the treatment of various diseases such as rheumatoid arthritis, ankylosing spondylitis, acute muscle pain conditions and osteoarthritis. Overdose of DIC can lead to renal injuries in both experimental animal and human. Our research was done to assess the protective role of silymarin on renal damage induced by DIC in rats. Methods: Thirty-two Wistar rats were assigned to four groups (n=8/group). Group 1 was control group; animals in group 2 were administrated DIC; Groups 3 and 4 administrated DIC plus silymarin with doses of 100 mg/kg and 200 mg/kg, orally (p.o), respectively. Various biochemical, molecular, and histological parameters were evaluated in serum and tissue homogenate. Results: In the second group, the levels of kidney catalase (CAT), vitamin C and superoxide dismutase (SOD) remarkably reduced (P &lt; 0.05) relative to the control group. Also, urea, creatinine (Cr), malondialdehyde (MDA), serum tumor necrosis factor-α (TNF-α) and gene expression of TNF-α in this group were noticeably elevated (P &lt; 0.05) relative to the control group. Treatment with silymarin caused a remarkable elevation (P &lt; 0.05) in vitamin C, SOD, CAT and a remarkable reduction (P &lt; 0.05) in the content of MDA, urea, Cr, TNF-α gene expression and serum TNF-α in comparison with second group. Histological injuries were also ameliorated by silymarin administration. Conclusion: The results confirm that silymarin has an ameliorative role against renal damage and oxidative stress induced by DIC in male rats.

Atipamezole is a promising non-discriminative inhibitor against pan-CYP450 including diclofenac 4′-hydroxylation: A comparison with ABT for drug ADME optimization and mechanism study

1-aminobenzotriazole (ABT) is a known P450 enzyme non-selective inactivator that serves as a tool for assessing P450-mediated metabolism. However, many findings demonstrated that ABT was ineffective with human CYP2C9. A profound pan-CYP450 inhibitor is desired avoid the risk of incomplete inhibition of P450, especially CYP2C9. Atipamezole is commonly used to recover animals from sedation-anesthesia induced by α2−adrenoceptor agonists. The purpose of this study is to evaluate atipamezole as a non-selective inhibitor of P450 enzymes and compare it with ABT. Inhibition toward seven major human CYP450 isoform was determined for atipamezole and ABT in human, rat, and dog liver microsomes for the direct and time-dependent inhibition potentials. IC50 values toward human and animal CYPs without preincubation are 0.02–7.93 μM and 20.9–1798 μM for atipamezole and ABT, respectively. The IC50 values of ABT after preincubation shift to 4.06–460 μM. Atipamezole has more effective inhibition to CYP2C9 mediated diclofenac hydroxylation in human and animal liver microsomes with IC50 values of 1.50–5.20 μM than that of ABT at 74.7-460 μM. No IC50 shift was observed for atipamezole to CYP isoforms. In vivo utility of atipamezole was assessed by co-dosing with diclofenac in rats. At 30 mg/kg via oral, atipamezole enhanced the AUC of diclofenac by 13.1-fold and the Cmax by 5.6-fold. Similar enhancement also achieved for ABT (100 mg/kg) with AUC and Cmax increased 9.5 and 4.8-fold. As a reversible pan-CYP inhibitor, atipamezole showed less species difference than ABT. It provides a better and easier to use alternative to ABT for ADME optimization and elucidating mechanistic drug metabolism or toxicity studies.

Effect of iguratimod on diclofenac metabolism by CYP2C9 in rats and human recombinant CYP2C9 yeast cells

Iguratimod (IGU, also known as T-614), a novel disease modifying antirheumatic drug intended to cure patients with rheumatoid arthritis (RA). The purpose of this study is to evaluate the effect of IGU on the pharmacokinetics of CYP2C9 probe drug diclofenac and its metabolite 4′-hydroxy diclofenac in vivo and in vitro. In in vivo experiments, 24 rats were randomly assigned to three groups consisting of the control group (Normal saline), low dose IGU group (10 mg/kg) and high dose IGU group (30 mg/ kg). Blood samples were collected from orbital sinuses vein before 1 hour and serial times of giving diclofenac (15 mg/kg) to all the rats. Plasma concentration of diclofenac and its metabolite 4´-hydroxy diclofenac were assayed by high performance liquid chromatography. Pharmacokinetic parameters were assessed by Winnonlin 6.4 pharmacokinetic software. Moreover, in vitro studies were performed in recombinant human CYP2C9 yeast cell system. IGU at low dose showed no significant differences in the pharmacokinetic parameters of diclofenac and 4-hydroxy diclofenac in vivo when compared with control group (p>0.005). However, at the high dose of IGU, the pharmacokinetic parameters of 4´-hydroxy metabolite of diclofenac increase in half-life (T1/2) and mean area under the curve (AUC0→24), while a decrease in mean clearance (CL, mL/h/kg) and volume of distribution Vz (mL/kg). In addition, in in vitro study, high doses of IGU reduces the metabolism rate of diclofenac. IGU at high dose significantly increase the pharmacokinetics parameters of 4´-hydroxy diclofenac in rats. Additionally, it also showed the potent inhibitory effect on diclofenac metabolism in recombinant human CYP2C9 yeast cells.

Syzygium aqueum: A Polyphenol- Rich Leaf Extract Exhibits Antioxidant, Hepatoprotective, Pain-Killing and Anti-inflammatory Activities in Animal Models.

Syzygium aqueum is widely used in folk medicine. A polyphenol-rich extract from its leaves demonstrated a plethora of substantial pharmacological properties. The extract showed solid antioxidant properties in vitro and protected human keratinocytes (HaCaT cells) against UVA damage. The extract also reduced the elevated levels of ALT, AST, total bilirubin (TB), total cholesterol (TC) and triglycerides (TG) in rats with acute CCl4 intoxication. In addition to reducing the high MDA level, the extract noticeably restored GSH and SOD to the normal control levels in liver tissue homogenates and counteracted the deleterious histopathologic changes in liver after CCl4 injection. Additionally, the extract exhibited promising anti-inflammatory activities in vitro where it inhibited LOX, COX-1, and COX-2 with a higher COX-2 selectivity than that of indomethacin and diclofenac and reduced the extent of lysis of erythrocytes upon incubation with hypotonic buffer solution. S. aqueum extract also markedly reduced leukocyte numbers with similar activities to diclofenac in rats challenged with carrageenan. Additionally, administration of the extract abolished writhes induced by acetic acid in mice and prolonged the response latency in hot plate test. Meanwhile, the identified polyphenolics from the extract showed a certain affinity for the active pockets of 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) explaining the observed anti-inflammatory activities. Finally, 87 secondary metabolites (mostly phenolics) were tentatively identified in the extract based on LC-MS/MS analyses. Syzygium aqueum displays good protection against oxidative stress, free radicals, and could be a good candidate for treating oxidative stress related diseases.

Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall–Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall–Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac.

Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats

The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1–31mg/kg), curcumin (3.1–100mg/kg) or the diclofenac–curcumin combination (2.4–38.4mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10mg/kg) was studied in presence and the absence of curcumin (31mg/kg). Diclofenac, curcumin, or diclofenac–curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2mg/kg) was significantly different from the observed experimental ED30 value (9.8mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac–curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain.

Reversal of Monoarthritis-induced Affective Disorders by Diclofenac in Rats

Nonsteroidal anti-inflammatory drugs are effective for arthritic pain, but it is unknown whether they also benefit anxiety and depression that frequently coexist with pain. Using the monoarthritis model, the authors evaluated the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in structures implicated in both sensorial and emotional pain spheres, and it was verified whether analgesia can reverse monoarthritis-mediated affective responses. Monoarthritis was induced in male rats by complete Freund's adjuvant injection. Allodynia (ankle-bend test), mechanical hyperalgesia (paw-pinch test), anxiety- and depression-like behaviors (elevated zero maze and forced swimming tests, respectively), and ERK1/2 phosphorylation (Western blot) in the spinal cord, paragigantocellularis nucleus, locus coeruleus, and prefrontal cortex were evaluated at 4, 14, and 28 days postinoculation (n = 6 per group). Changes in these parameters were evaluated after induction of analgesia by topical diclofenac (n = 5 to 6 per group). Despite the pain hypersensitivity and inflammation throughout the testing period, chronic monoarthritis (28 days) also resulted in depressive- (control [mean ± SEM]: 38.3 ± 3.7 vs. monoarthritis: 51.3 ± 2.0; P < 0.05) and anxiogenic-like behaviors (control: 36.8 ± 3.7 vs. monoarthritis: 13.2 ± 2.9; P < 0.001). These changes coincided with increased ERK1/2 activation in the spinal cord, paragigantocellularis, locus coeruleus, and prefrontal cortex (control vs. monoarthritis: 1.0 ± 0.0 vs. 5.1 ± 20.8, P < 0.001; 0.9 ± 0.0 vs. 1.9 ± 0.4, P < 0.05; 1.0 ± 0.3 vs. 2.9 ± 0.6, P < 0.01; and 1.0 ± 0.0 vs. 1.8 ± 0.1, P < 0.05, respectively). Diclofenac decreased the pain threshold of the inflamed paw and reversed the anxio-depressive state, restoring ERK1/2 activation levels in the regions analyzed. Chronic monoarthritis induces affective disorders associated with ERK1/2 phosphorylation in paragigantocellularis, locus coeruleus, and prefrontal cortex which are reversed by diclofenac analgesia. (Anesthesiology 2014; 120:1476-90).

Possible Potentiation by Certain Antioxidants of the Anti-Inflammatory Effects of Diclofenac in Rats

In the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agent per se.

A simple high performance liquid chromatography method for determination of rebamipide in rat urine

Rebamipide is a mucoprotective agent commonly used to prevent nonsteriodal anti-inflammatory drug-induced gastrointenstinal side effects [1]. Human plasma and urine analysis of rebamipide utilizing high performance liquid chromatography (HPLC) have been reported [2]. Recently, we reported on the plasma levels of rebamipide in presense or absence of celecoxib or diclofenac in rats [3] using a modified HPLC method of detection developed by Jeoung et al. [4]. To tailor the method towards use in urinary rebamipide extraction and analysis, the following modifications were made:•To compensate for high concentrations of rebamipide found in urine, a new rebamipide stock solution was prepared with a final concentration of 50,000ng/mL.•Rat urine calibration standards were obtained within the range of 50–1000ng/mL and 1000–50,000ng/mL.•Plasma samples were replaced with urine samples.