Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level

Günaydın, Caner; Bilge, S. Sırrı

doi:10.5152/eurasianjmed.2018.0010

Cited by 183 publications

(132 citation statements)

References 48 publications

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“…l‐selectin shedding; inhibition of i‐NOS; inhibition of NF‐Kappa B; suppression metaloproteinasas; inhibition of ß2 integrin activation; activation of α 2 ‐adrenoeptor; increase of IL‐1ß; upregulation IL‐6 (Diaz‐Gonzalez & Sanchez‐Madrid, ; Dwivedi et al, ; Gunaydın & Bilge, ; Hamza & Dionne, ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, increasing evidence suggests other molecular mechanisms, such as the interaction with monoaminergic and cholinergic systems, inhibition of i‐NO production, tumor necrosis factor, nuclear factor kappa B, downregulation of L‐selecting expression. Additionally, other NSAIDs properties have been described including cell adhesion (Hamza & Dionne, ; Diaz‐Gonzalez & Sanchez‐Madrid, ; Dwivedi, Gurjar, Kumar, & Singh, ; Gunaydın & Bilge, ).…”

Section: Introductionmentioning

confidence: 99%

“…NSAIDs participate in various functions at the cellular level, whereby PGs are found in several regions of the CNS, and consequently COXs are expressed, for example, in the hippocampus, cerebral cortex, amygdala, and various brain regions (Gunaydın & Bilge, ; Yagami, Koma, & Yamamoto, ). In agreement with the distribution profile of PGs in different regions of the CNS, drugs, which affect this system, could modulate the effect of NSAIDs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain

Vargas¹,

Miranda

Sierralta

et al. 2019

Drug Development Research

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Nonsteroidal anti-inflammatory drugs (NSAIDs) possess as primary action mechanism the inhibition of cyclooxygenases (COX-1, COX-2, and COX-3), thus producing a decreasing prostaglandin synthesis. This study was designed to evaluate whether the antinociception induced by NSAIDs could be modulated by clomipramine or risperidone using a chemical model of inflammatory acute visceral pain, the abdominal acetic acid induced a writhing test in mice.Dose-response curves, intraperitoneal, or intrathecal for the antinociceptive activity displayed by ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol were analyzed in order to obtain the ED 50 of each drug. Pretreatment of mice with either clomipramine or risperidone, increased antinociceptive potency of ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol, expressed by a decrease in the values of antinociceptive ED 50. The results that were obtained are in line with those where the inhibition of COXs provides a justification for most of the pharmacological actions. Nevertheless, several findings suggest other molecular mechanisms, among which may be mentioned, L-selecting shedding; inhibition of i-NOS; inhibition of NF-Kappa B; suppression metaloproteinasas; inhibition of ß2 integrin activation; activation of α 2 -adrenoceptor; increase of IL-1ß; upregulation IL-6. In conclusion, the data generated in this study demonstrated that risperidone and clomipramine, separately, increase antinociceptive potency of NSAIDs in a chemical model of inflammatory acute visceral tonic pain. K E Y W O R D S clomipramine, mouse visceral pain, NSAIDs, pharmacological interaction, risperidone, tonic pain

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain

Vargas¹,

Miranda

Sierralta

et al. 2019

Drug Development Research

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“…Acetylsalicylic acid reduced the pro-inflamma- tory prostaglandin, PGE2, which was higher in GK/Jcl rats. APAP and acetylsalicylic acid suppress the production of PGE2 via inhibition of COX activity (Gunaydin and Bilge, 2018). PGE2 may contribute to diabetes via EP3, a PGE2receptor, by inhibiting insulin secretion leading to impaired glucose tolerance and insulin sensitivity (Nasrallah et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Preexisting diabetes mellitus had no effect on the no-observed-adverse-effect-level of acetaminophen in rats

et al. 2020

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Information on the safety of chemical substances in patients with various preexisting conditions remains limited. Acetaminophen was added to the basal diet at 0, 80, 253, 800, 2530, or 8000 ppm and administered to type 2 diabetes mellitus rats (GK/Jcl) and the control male rats (Wistar) for 13 weeks. Both strains treated with 8000 ppm acetaminophen (561.4 and 567.7 mg/kg body weight/ day, GK/Jcl and Wistar rats, respectively) showed decreased levels of red blood cell counts, blood urea nitrogen, creatinine, and total bilirubin compared to those of non-treated rats. Treatment with 8000 ppm of acetaminophen reduced the blood glucose and hemoglobin A1c levels of GK/Jcl rats. An increase in the relative weights of the kidneys and liver, and a decrease in the weight of the salivary glands were observed in both GK/Jcl and Wistar rats treated with 8000 ppm acetaminophen relative to those of nontreated control rats. Microscopically, both strains treated with 2530 (174.3 and 164.2 mg/kg body weight/ day, GK/Jcl and Wistar rats, respectively) or 8000 ppm acetaminophen showed hepatocellular hypertrophy and degenerative lesions in the salivary glands, whereas similar lesions were not observed in nontreated rats. In conclusion, the no-observed-adverse-effect-level of acetaminophen was 800 ppm in both diabetic and control rats.

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“…In addition to inhibition of cyclooxygenase they also can activate PPAR (peroxisome proliferator activator receptor) α, increase expression of heat shock proteins and regulate the cytoskeleton through the Rho kinase pathway. [120]. In SLE T cells, genetically enforced increased expression of HRES-1/Rab4 causes the accumulation of oxidative stress-generating mitochondria [37] and activation of mTORC1 [121].…”

Section: Effects Of Biologics Small Molecule Inhibitors and Nsaids Omentioning

confidence: 99%

Metabolic Targets for Treatment of Autoimmune Diseases

2020

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There is a considerable unmet demand for safe and efficacious medications in the realm of autoimmune and inflammatory diseases. The fate of the immune cells is precisely governed by control of various metabolic processes such as mitochondrial oxidative phosphorylation, glycolysis, fatty acid synthesis, beta-oxidation, amino acid metabolism, and several others including the pentose phosphate pathway, which is a unique source of metabolites for cell proliferation and maintenance of a reducing environment. These pathways are tightly regulated by the cytokines, growth factors, availability of the nutrients and host-microbe interaction. Exploring the immunometabolic pathways that govern the fate of cells of the innate and adaptive immune system, during various stages of activation, proliferation, differentiation and effector response, is crucial for new development of new treatment targets. Identifying the pathway connections and key enzymes will help us to target the dysregulated inflammation in autoimmune diseases. The mechanistic target of rapamycin (mTOR) pathway is increasingly recognized as one of the key drivers of proinflammatory responses in autoimmune diseases. In this review, we provide an update on the current understanding of the metabolic signatures noted within different immune cells of many different autoimmune diseases with a focus on selecting pathways and specific metabolites as targets for treatment.

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Effects of Nonsteroidal Anti-Inflammatory Drugs at the Molecular Level

Cited by 183 publications

References 48 publications

Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain

Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain

Preexisting diabetes mellitus had no effect on the no-observed-adverse-effect-level of acetaminophen in rats

Metabolic Targets for Treatment of Autoimmune Diseases

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