Novel 1,2,4-Triazolo[1,5-<i>a</i>]pyridines and Their Fused Ring Systems Attenuate Oxidative Stress and Prolong Lifespan of Caenorhabiditis elegans

BackgroundCisplatin (CP) is known as a potent anti-cancer drug. The most therapeutic adverse effect of CP is induced hepatotoxicity. In the present study, the protective effect of thymoquinone (TQ) on CP-induced hepatotoxicity was studied.MethodsWistar rats were divided into three groups (15 rats each). Group 1 served as the control group. Group 2 rats were injected ip with a single dose of CP (12 mg/kg b.w, i.p.). Group 3 rats were orally pre-treated with TQ (500 mg. kg−1. day−1) for one month, then the animals were injected i.p with CP 12 mg.kg−1.ResultsThe beneficial effects of TQ with its antioxidant/anti-inflammatory effects were observed. Injection of rats with CP markedly affected the liver functions and histopathological changes. The antioxidant enzyme activities and reduced glutathione (GSH) contents were significantly decreased while the levels of malondialdehyde (MDA) significantly increased. The electromobility shift assay (EMSA) showed a significant activation of NF-κB-p65 in the rat liver injected with CP. Furthermore, the expression and concentrations of inflammatory tumor necrosis factor (TNF-α), nitric oxide synthetase (iNOS), and interleukin (IL-1β) were markedly elevated in the CP injected rats. The administration of TQ improved all the altered functions, histopathology of the liver and attenuated the activated NF-κB. The antioxidant enzyme activities (glutathione peroxidase and glutathione –S transferase) of the rat livers were markedly increased while MDA was reduced as a result of TQ administration. In addition, the expression of TNF-α, iNOS, and IL-1β were markedly reduced.ConclusionIt was concluded that, TQ has potential benefits in the prevention of the onset and progression of CP induced hepatotoxicity.

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“…Malondialdehyde (MDA) was assayed using the method described [20, 21]. The concentration of MDA was calculated and expressed as nmol .…”

Section: Methodsmentioning

confidence: 99%

Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa- β

Al-Malki

Sayed

2014

BMC Complement Altern Med

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“…This means that these amines are not susceptible by Folin reagent oxidation, electron transfer from DPPH radical, and not involved in the enzymatic reaction because lacking of phenolic structure essential for the enzymatic coupling reaction [16]. Moreover, triazolopyridines derivatives, which do not contain (poly)phenolic groups but primary and tertiary amino groups, similarly to the examined biogenic amines, appear to acts directly and indirectly as an efficient ROS scavenging in vivo, as found by measuring the concentration of malondialdehyde by paraquat-induced lipid peroxidation [18].…”

Section: Resultsmentioning

confidence: 99%

<i>In Vitro</i> Preliminary Evidences on the Antioxidant Properties of Biogenic Amines

Stevanato¹,

Bertelle²,

Fabris³

2013

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Antioxidant properties of the principal biogenic amines were determined in vitro by four analytical methods-Folin Ciocalteu, DPPH, enzymatic and inhibition of lipid peroxidation-in order to avoid possible measuring-method linked mistakes. Different results are obtained, depending on the parameters that each of them measures. The combination of the data indicates that all examined amines show antioxidant characteristics: in particular, tyramine, serotonin, L-norepinephrine, (-)-epinephrine and dopamine owing to their (poly)phenolic structure too, while aliphatic polyamines-spermine, spermidine, putrescine and cadaverine-histamine, melatonin and tryptamine appear to act specifically on the oxygen-consuming species involved in the lipid peroxidation of polyunsaturated fatty acids.

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“…This group of geroprotectors includes: chelators of Cu and Fe, for example, EDTA which can extend the lifespan of C. elegans [51], and R. norvegicus [52];ROS-scavengers, as exemplified by ethoxiquin which extends the lifespan of M. musculus [53];compounds that attenuate the formation of advanced glycation end products, for example, a polyphenol plant butein that is known to increase the replicative lifespan of S. cerevisiae [42], and 1,2,4-triazolo [1,5-a] pyridines that prolong the lifespan of nematodes [54];anti-amyloid agents, such as polyphenols and curcumin which seem to inhibit the formation of amyloids from different proteins [55-59]. Tetrahydrocurcumin and green tea polyphenols extended the lifespan of C57BL/6 mice [60] but curcumin and tea polyphenols failed to extend the lifespan of F1 hybrid mice [61].…”

Section: Classification Of Geroprotectors Based On the Concept Of Hommentioning

confidence: 99%

“…compounds that attenuate the formation of advanced glycation end products, for example, a polyphenol plant butein that is known to increase the replicative lifespan of S. cerevisiae [42], and 1,2,4-triazolo [1,5-a] pyridines that prolong the lifespan of nematodes [54];…”

Section: Classification Of Geroprotectors Based On the Concept Of Hommentioning

confidence: 99%

Geroprotectors: A Unified Concept and Screening Approaches

et al. 2017

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Although the geroprotectors discovery is a new biomedicine trend and more than 200 compounds can slow aging and increase the lifespan of the model organism, there are still no geroprotectors on the market. The reasons may be partly related to the lack of a unified concept of geroprotector, accepted by the scientific community. Such concept as a system of criteria for geroprotector identification and classification can form a basis for an analytical model of anti-aging drugs, help to consolidate the efforts of various research initiatives in this area and compare their results. Here, we review the existing classification and characteristics of geroprotectors based on their effect on the survival of a group of individuals or pharmaceutics classes, according to the proposed mechanism of their geroprotective action or theories of aging. After discussing advantages and disadvantages of these approaches, we offer a new concept based on the maintenance of homeostatic capacity because aging can be considered as exponential shrinkage of homeostatic capacity leading to the onset of age-related diseases and death. Besides, we review the most promising current screening approaches to finding new geroprotectors. Establishing the classification of existing geroprotectors based on physiology and current understanding of the nature of aging is essential for putting the existing knowledge into a single system. This system could be useful to formulate standards for finding and creating new geroprotectors. Standardization, in turn, would allow easier comparison and combination of experimental data obtained by different research groups.

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Novel 1,2,4-Triazolo[1,5-a]pyridines and Their Fused Ring Systems Attenuate Oxidative Stress and Prolong Lifespan of Caenorhabiditis elegans

Cited by 49 publications

References 47 publications

Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa- β

Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa- β

<i>In Vitro</i> Preliminary Evidences on the Antioxidant Properties of Biogenic Amines

Geroprotectors: A Unified Concept and Screening Approaches

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Novel 1,2,4-Triazolo[1,5-a]pyridines and Their Fused Ring Systems Attenuate Oxidative Stress and Prolong Lifespan of Caenorhabiditis elegans

Cited by 49 publications

References 47 publications

Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa- β

Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa- β

&lt;i&gt;In Vitro&lt;/i&gt; Preliminary Evidences on the Antioxidant Properties of Biogenic Amines

Geroprotectors: A Unified Concept and Screening Approaches

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<i>In Vitro</i> Preliminary Evidences on the Antioxidant Properties of Biogenic Amines