Differential role of cyclooxygenase isozymes on neuronal density in hippocampus CA1 region of intracerebroventricular streptozotocin treated rat brain

Dhull, Dinesh K.; Bhateja, Deepak; Dhull, Rakesh K.; Padi, Satyanarayana S. V.

doi:10.1016/j.jchemneu.2011.10.001

Cited by 19 publications

(5 citation statements)

References 26 publications

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“…Therefore, regarding STZ action on the pancreas, our data present clear evidence for a protective role of PTGS-2. Interestingly a recent work on STZ-induced neurodegeneration in rats suggested a deleterious role of PTGS-2 (34). An explanation for this difference could be that the PTGS-2/prostanoid pathway is acting differentially and organ dependent.…”

Section: Discussionmentioning

confidence: 99%

PTGS-2–PTGER2/4 Signaling Pathway Partially Protects From Diabetogenic Toxicity of Streptozotocin in Mice

et al. 2012

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Prostanoids are suggested to participate in diabetes pathology, but their roles are controversially discussed. The purpose of the current study was to examine the role of cyclooxygenase (prostaglandin synthase [PTGS]) enzymes and prostaglandin (PG) E2 signaling pathways in streptozotocin (STZ)-induced type 1 diabetes. Blood glucose, insulin, and survival rate were studied in mice with targeted disruption of the genes for PTGS and PGE receptors (PTGERs). PGE2 was found as the main prostanoid formed by the pancreas. Contrarily to PTGS-1, deficiency of PTGS-2 activity significantly amplified STZ effect, causing dramatic loss of insulin production and rise in blood glucose and death rate. STZ metabolism was unaffected by PTGS deficiency. Diabetogenicity of STZ in PTGER1−/−, PTGER2−/−, PTGER3−/−, and PTGER4−/− mice was comparable to control mice. In striking contrast, combined knockout of PTGER2 and PTGER4 by blocking PTGER4 in PTGER2−/− mice strongly enhanced STZ pathology. Treatment of PTGS-2−/− and wild-type mice with PTGER2/PTGER4 agonists partially protected against STZ-induced diabetes and restored β-cell function. Our data uncover a previously unrecognized protective role of PTGS-2–derived PGE2 in STZ-induced diabetes mediated by the receptor types PTGER2 and PTGER4. These findings offer the possibility to intervene in early progression of type 1 diabetes by using PTGER-selective agonists.

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Section: Discussionmentioning

confidence: 99%

PTGS-2–PTGER2/4 Signaling Pathway Partially Protects From Diabetogenic Toxicity of Streptozotocin in Mice

et al. 2012

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“…Similar lack of amyloid burden-clearing activity of celecoxib (and ibuprofen) has been found in APP/PS1 transgenic mice AD model in which COX-1 preferring inhibitor flurbiprofen administered in a diet, dramatically reduced amyloid plaque and nonfibrillar deposit burden (Jantzen et al 2002). In the experiment on STZ-icv rat model, selective inhibitors of COX-1 (valeryl salicylate, 5 and 10 mg/kg), COX-2 (etoricoxib, 5 and 10 mg/kg) or COX-3 (phenacetin, 20 and 40 mg/kg) were administered daily for 21 days, intraperitoneally (Dhull et al 2012a). In comparison with the control animals, COX-1 and COX-2 inhibitors significantly increased the survival of hippocampus CA1 neurons in the STZ-icv treated rats in a dose dependent manner while COX-3 inhibitor had no effect, suggesting the differential role of COX isoenzymes in neuronal death in hippocampal CA1 regions in the STZ-icv rat sAD model.…”

Section: Drugs With Predominant Anti-inflammatory Activitymentioning

confidence: 99%

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

et al. 2012

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“…We used the following two NSAIDs for our study: ibuprofen, a non-selective inhibitor (IC 50 = 15 μg/mL), and etoricoxib, a selective COX-2 inhibitor (IC 50 = 0.0029 μg/mL). 17 The selected doses of ibuprofen (40 mg/kg) and etoricoxib (10 mg/kg) were determined with a two-step method: a review of the doses used in previous animal studies that evaluated the anti-inflammatory properties of these drugs; [18][19][20][21] and the calculation of an equivalent dose using the mathematical formula based on body surface area (BSA) suggested by the Food and Drug Administration (FDA). 22 The doses of ibuprofen and etoricoxib selected for our animal model are equivalent to 400 mg and 100 mg in humans, respectively.…”

Section: Discussionmentioning

confidence: 99%

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

et al. 2016

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The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

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Differential role of cyclooxygenase isozymes on neuronal density in hippocampus CA1 region of intracerebroventricular streptozotocin treated rat brain

Cited by 19 publications

References 26 publications

PTGS-2–PTGER2/4 Signaling Pathway Partially Protects From Diabetogenic Toxicity of Streptozotocin in Mice

PTGS-2–PTGER2/4 Signaling Pathway Partially Protects From Diabetogenic Toxicity of Streptozotocin in Mice

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

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