Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Blood Pressure and Hematological Indices in Rats

Vasilchuk, A. G.; Ivanova, E. A.; Matyushkin, A. I.; Алексеева, Светлана; Kachalov, K. S.; Воронина, Т. А.

doi:10.3103/s0096392522010059

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…Fatalities of rats with AA were only registered in the diclofenac gel group (4 rats out of 10). This result reproduces our previous findings, 50 the only difference being that diclofenac gel was previously applied daily starting one day before the FCA injection. Notably, in the previous study, no fatalities among rats with AA were observed in the group that received daily intraperitoneal injections of 5 mg/kg diclofenac sodium for 14 days.…”

Section: Discussionsupporting

confidence: 91%

“…Diclofenac sodium administered orally at the same daily dose for 21 days caused the death of 4 out of 10 rats due to enteropathy, which was identified by iron-deficiency anemia, thinning of the gastric and intestinal walls, bile reflux in the stomach, and almost no food residue in the gastrointestinal tract. 50 In the present study, rats treated with gels applied locally to the hind paws exhibited no such signs.…”

Section: Discussioncontrasting

confidence: 45%

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Low-affinity NMDA receptor antagonist hemantane in a topical formulation attenuates arthritis induced by Freund’s Complete Adjuvant in rats

Ivanova¹,

Matyushkin²,

Sorokina³

et al. 2023

Adv Pharm Bull

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Objective: N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund’s Complete Adjuvant (FCA). Methods: On day 14 after an FCA injection into the left hind paw, rats with contralateral hind paw edema were selected for further investigation (29/65). They were treated with 5% Hemantane gel or 1% Diclofenac gel applied locally to hind paws daily for 2 weeks starting 14 days after the FCA injection. Rats with arthritis were examined hind paw edema, hyperalgesia, and motor deficits; their body weight and hematological parameters were recorded. The rats were euthanized on day 28, followed by histological examination of the ankle joint (HE stain). Results: Rats with arthritis exhibited hind paw inflammation and hyperalgesia, motor deficits, changes of hematological parameters, reduced weight gain and spleen hypertrophy. Histological examination of the ankle joint revealed degenerative-dystrophic lesions of the cartilaginous tissue, proliferative inflammation of the synovium, edema and lymphocytic/macrophage infiltration of periarticular tissues. Hemantane gel reduced hind paw edema, pain, motor deficits and histological signs of inflammation; its effect was comparable to diclofenac gel. Conclusion: Hemantane gel alleviates FCA-induced arthritis in rats, and its effect is comparable to diclofenac gel.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 45%

Low-affinity NMDA receptor antagonist hemantane in a topical formulation attenuates arthritis induced by Freund’s Complete Adjuvant in rats

Ivanova¹,

Matyushkin²,

Sorokina³

et al. 2023

Adv Pharm Bull

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“…During NSAID administration, both selective COX-2 inhibitors and non-selective COX inhibitors reduce the PG level in kidneys and impair the renal hemodynamics. Renal effects of these drugs are thought to cause arterial hypertension [29]. Expression of the COX enzyme covers almost all peripheral organs of the body including lungs, liver, kidneys, stomach, colon, thyroid gland, pancreas, uterus, testis and others [30].…”

Section: Discussionmentioning

confidence: 99%

Histopathological effects on kidney of diclofenac potassium and diazepam used in an experimental epilepsy model

Şaylan¹,

Turel²,

Türel³

et al. 2023

j-ebr

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To investigate the effects of diazepam, which has anticonvulsant and anxiolytic effects, and diclofenac potassium, which has anti-inflammatory, analgesic and antipyretic effects, on rat kidney tissue, used in an experimental epilepsy model. Methods: 32 Wistar albino rats (2-4 months old, 200-250 gr) were used in the study. The rats were grouped in four as 8 rats in each group: Epilepsy, Epilepsy + Diazepam, Epilepsy + Diclofenac potassium, Epilepsy + Diazepam + Diclofenac potassium. Epileptic seizure model was created with penicillin (500.000 IU) injected intracortically under urethane anesthesia. 30 minutes later, diazepam (0.1 mg/kg) and diclofenac potassium (10 mg/kg) were administered intraperitoneally. At the end of the study, rat kidneys were removed and evaluated histopathologically in terms of inflammation, glomerular shrinkage, tubular dilatation, tubular epithelial thinning, desquame epithelium, brush epithelial loss, vacuolization, hemorrhage and congestion. Results: No difference was found between diazepam and diclofenac potassium in terms of vacuolization, glomerular shrinkage, tubular dilatation and hemorrhage. Inflammation, congestion and tubular epithelial thinning rate were found to be lower inEpilepsy + Diclofenac potassium and Epilepsy + Diazepam + Diclofenac potassium group when compared with Epilepsy + Diazepam group. While brush epithelial loss and desquame epithelial rate was found to be lowest in the epilepsy group, these parameters were not found to show a significant difference between drug groups. Conclusion: It was concluded that combined use of diazepam and diclofenac potassium in their effects on kidney are more useful than their single use.

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Effect of multiple-dose regimens of cyclooxygenase inhibitors and their combinations with mexidol on behavior in mature rats

Ivanova

Vasilchuk

Matyushkin

et al. 2023

Fk&Fd

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Effects of multiple-dose regimens (oral, daily, once a day for 15 days) of cyclooxygenase (COX) inhibitors etoricoxib (1 and 10 mg/kg), diclofenac sodium (1 and 5 mg/kg) and their combinations with 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol 25 mg/kg) on rat behavior were studied in the open field test, rotarod test and elevated plus maze test. Exploratory (in open field test) and locomotor (in rotarod test) behavior of rats was significantly weakened only by the non-selective COX inhibitor diclofenac sodium at 5 mg/kg, which is due to the peripheral side effect of the drug. The selective COX-2 inhibitor etoricoxib increased the time in the central area of the elevated plus maze at 1 and 10 mg/kg and reduced the latent period of locomotion in the open field test at 10 mg/kg. A combination of diclofenac sodium (1 mg/kg) with mexidol neither reduced exploratory behavior nor caused motor deficit in contrast to diclofenac sodium at 5 mg/kg. However, a combination of etoricoxib (1 mg/kg) with mexidol inhibited locomotor activity in the rotarod test. Nevertheless, it produced no significant effects on the exploratory behavior or anxiety of animals in the open field test and elevated plus maze test.

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Effect of Cyclooxygenase Inhibitors Etoricoxib and Diclofenac Sodium and Their Combinations with Mexidol on Blood Pressure and Hematological Indices in Rats

Cited by 3 publications

References 15 publications

Low-affinity NMDA receptor antagonist hemantane in a topical formulation attenuates arthritis induced by Freund’s Complete Adjuvant in rats

Low-affinity NMDA receptor antagonist hemantane in a topical formulation attenuates arthritis induced by Freund’s Complete Adjuvant in rats

Histopathological effects on kidney of diclofenac potassium and diazepam used in an experimental epilepsy model

Effect of multiple-dose regimens of cyclooxygenase inhibitors and their combinations with mexidol on behavior in mature rats

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