Indole-3-guanylhydrazone hydrochloride mitigates long-term cognitive impairment in a neonatal sepsis model with involvement of MAPK and NFκB pathways

Heimfarth, Luana; Carvalho, Alexandra M.S.; Quintans, Jullyana de Souza Siqueira; Pereira, Erik Willyame Menezes; Lima, Natália Teles; Carvalho, Mikaella Tuanny Bezerra; Barreto, Rosana S.S.; Moreira, José Cláudio Fonseca; Silva-Júnior, Edeildo Ferreira da; Schmitt, Martine; Bourguignon, Jean‐Jacques; Aquino, Thiago Mendonça de; Araújo-Júnior, João Xavier de; Quintans‐Júnior, Lucindo J.

doi:10.1016/j.neuint.2019.104647

Cited by 8 publications

(4 citation statements)

References 93 publications

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“…The mechanism of compound 65 was connected to a decreased pro-inflammatory cytokine release and COX-2 expression, as well as the suppression of microglia activation. Additionally, septic mice treated with derivative 65 did not exhibit the cognitive impairment and the anxiety behavior caused by LPS [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

A Review of the Biological Activity of Amidrazone Derivatives

et al. 2022

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Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010–2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research.

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Section: Resultsmentioning

confidence: 99%

A Review of the Biological Activity of Amidrazone Derivatives

et al. 2022

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“…The aminoguanidine derivative indole-3-guanylhydrazone hydrochloride (LQM01) has been shown to have anti-inflammatory, antihypertensive, and antioxidant properties. Anxiety-like behavior and cognitive impairment induced by LPS in adult mice were reduced via LQM01 exposure during the neonatal period, which also attenuated inflammatory reactions and oxidative damage through the MAPK and NF-κB signaling pathways and microglial activation suppression [74]. Overall, these signaling pathways are critical in the progression of microglial activation through SAE, and a potential anti-SAE treatment target is blocking the above signaling pathways.…”

Section: Signaling Pathway Inhibitorsmentioning

confidence: 97%

Microglial Activation: Key Players in Sepsis-Associated Encephalopathy

Hu,

Xie,

Zhang

et al. 2023

Brain Sciences

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Sepsis-associated encephalopathy (SAE) is a common brain dysfunction, which results in severe cognitive and neurological sequelae and an increased mortality rate in patients with sepsis. Depending on the stimulus, microglia (resident macrophages in the brain that are involved in SAE pathology and physiology) can adopt two polarization states (M1/M2), corresponding to altered microglial morphology, gene expression, and function. We systematically described the pathogenesis, morphology, function, and phenotype of microglial activation in SAE and demonstrated that microglia are closely related to SAE occurrence and development, and concomitant cognitive impairment. Finally, some potential therapeutic approaches that can prime microglia and neuroinflammation toward the beneficial restorative microglial phenotype in SAE were outlined.

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“…Preclinical studies have revealed the ability of certain guanylhydrazone derivatives to control pain and inflammation in different experimental models in vivo [19,45]. Carrageenan-induced pleurisy was performed to evaluate the anti-inflammatory potential of LQM10.…”

Section: Effects Of Lqm10 On Carrageenaninduced Pleurisymentioning

confidence: 99%

LQM10, a guanylhydrazone derivative, reduces nociceptive and inflammatory responses in mice

Noé

Ferro

Rodrigues

et al. 2023

Fundamemntal Clinical Pharma

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In the present study, we examined the antinociceptive and anti-inflammatory activities of a guanylhydrazone derivative, (E)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-guanylhydrazone hydrochloride (LQM10), in mice. The antinociceptive effect was determined by assessing behavioural responses in different pain models, while anti-inflammatory activity was examined in carrageenan-induced pleurisy. Intraperitoneal LQM10 administration reduced the acetic acid-induced nociceptive behaviour, a phenomenon that was unaltered by pretreatment with yohimbine, atropine, naloxone or glibenclamide. In the formalin assay, LQM10 reduced nociceptive behaviour only in the second phase, indicating an inhibitory effect on inflammatory pain. LQM10 did not alter the pain latency in the hot plate assay and did not impact the locomotor activity of mice in the rotarod assay. In the carrageenan-induced pleurisy assay, LQM10 treatment inhibited critical events involved in inflammatory responses, namely, leucocyte recruitment, plasma leakage and increased inflammatory mediators (tumour necrosis factor Like Properties of Chalchones and Flavonoid Derivatives [TNF]-α and interleukin [IL]-1β) in the pleural exudate. Overall, these results indicate that LQM10 exhibits antinociceptive effects associated with peripheral mechanisms and anti-inflammatory activity mediated via a reduction in leucocyte migration and proinflammatory mediators, rendering this compound a promising candidate for treating pain and inflammatory process.

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Indole-3-guanylhydrazone hydrochloride mitigates long-term cognitive impairment in a neonatal sepsis model with involvement of MAPK and NFκB pathways

Cited by 8 publications

References 93 publications

A Review of the Biological Activity of Amidrazone Derivatives

A Review of the Biological Activity of Amidrazone Derivatives

Microglial Activation: Key Players in Sepsis-Associated Encephalopathy

LQM10, a guanylhydrazone derivative, reduces nociceptive and inflammatory responses in mice

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