Effects of prolonged agmatine treatment in aged male Sprague–Dawley rats

Rushaidhi, M.; Zhang, H.; Liu, P.

doi:10.1016/j.neuroscience.2013.01.004

Cited by 34 publications

(23 citation statements)

References 63 publications

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“…It is also known that AGM has hepatoprotective effects that may be related to its ability to suppress oxidative stress, NO synthesis and TNF-α production (El-Agamy et al 2014;Rushaidhi et al 2013). The beneficial effect of AGM could relate to the ability of AGM to inhibit iNOS or to block NMDA receptors and/or voltage-dependent Ca 2+ channels (Yang and Reis 1999).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of agmatine in acute chlorpromazine hepatotoxicity in rats

Dejanović¹,

Stevanović²,

Ninković³

et al. 2014

Acta Vet. Brno

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The present study focused on potentially beneficial effects of agmatine on oxidative stress development in the liver during chlorpromazine treatment in rats. We wanted to examine the role of reactive oxygen species and efficiency of antioxidant protection through the determination of malondylaldehyde and total glutathione concentrations in rat liver homogenate, as well as plasma concentrations of malonylaldehyde and sulfhydryl groups after the treatment. Also, liver tissue sections were examined to follow histological changes. Chlorpromazine was applied intraperitoneally at a single dose of 38.7 mg/kg b.w. The second group was treated with both chlorpromazine (at a single dose of 38.7 mg/kg b.w.) and agmatine (at a single dose of 75 mg/kg b.w.). Agmatine was applied immediately after the chlorpromazine. The control group was treated with 0.9% saline solution in the same manner. Rats were sacrificed by decapitation 24 h after the treatment and biochemical and immunohistochemical examinations were performed. Analysis of data showed that treatment with agmatine significantly attenuated the oxidative stress indicators as evidenced by lowering malonylaldehyde concentrations in the liver and in plasma while not affecting liver concentrations of total glutathione and plasma concentration of sulfhydryl groups. Additionally, histological evaluation revealed the improvement of liver damage in this respect. The presented data indicated that intraperitoneally administered agmatine protects against chlorpromazine-induced liver disease in rats.

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Section: Discussionmentioning

confidence: 99%

Protective effect of agmatine in acute chlorpromazine hepatotoxicity in rats

Dejanović¹,

Stevanović²,

Ninković³

et al. 2014

Acta Vet. Brno

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“…Terapijski potencijal AGM kao suplementa ukoliko se primenjuje 4-6 nedelja svakodnevno potvrđen je kod odraslih pacova kako na bihejvioralnom, tako i na neurohemijskom nivou (10). Dokazana je i povećana koncentracija AGM u plazmi kod nekih psihijatrijskih oboljenja (shizofrenija i depresija) (11,12).…”

Section: Uvodunclassified

“…Takođe su poznati toksični efekti HPZ na kardiovaskularni sistem kao posledica blokiranja holinergičkih i α adrenergičkih receptora (56). Sa druge strane, terapijski potencijal AGM kao suplementa potvrđen je kod odraslih pacova na bihejvioralnom (poboljšava prostorno učenje u vodenom lavirintu) i neurohemijskom nivou (smanjuje aktivnost azot oksid sintaze) (10). Iako je poznat više od 100 godina, zbog mnogo kontroverzi, biosinteza AGM je kod ljudi nedovoljno poznata (12), uključujući i njegov uticaj na toksikokinetiku HPZ.…”

Section: Diskusijaunclassified

Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats

Dejanović¹,

Ninković²,

Stojanović³

et al. 2015

Arh farmaciju

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Ovа studijа se bavi ispitivanjem potencijаlno zaštitinih efekata аgmаtina (AGM) nа razvoj oksidаtivnog/nitrozativnog stresa u selektivno osetljivim strukturama mozga pacova nakon davanja hlorpromаzina (HPZ). Sve ispitivane supstance aplikovane su u pojedinačnoj dozi intraperitonealno (i.p.). Životinje su podeljene na kontrolnu (K, 0.9 % fiziološki rastvor), HPZ (HPZ, 38.7 mg/kg TM), HPZ+AGM (AGM, 75 mg/kg TM odmah nakon HPZ, 38.7 mg/kg TM i.p.) i AGM (AGM, 75 mg/kg TM) grupu i žrtvovane dekapitacijom 24 h nakon odgovarajućeg tretmana. Rezultаti pokаzuju dа primena HPZ sa AGM značajno smanjuje koncentraciju leka u mozgu pacova u poređenju sа HPZ-životinjаmа (p<0.05). Aplikacija HPZ povećava lipidnu peroksidaciju (p<0.001 u korteksu, strijatumu i hipokampusu), koncentraciju nitrita i nitrata (p<0.001 u sva tri ispitivana regiona mozga) i stvaranje superoksidnog anjon radikala (p<0.05 u sve tri moždane strukture) u odnosu na odgovarajuću kontrolu, dok istovremeno utiče na oštećenje enzimskog antioksidativnog sistema (superoksid dizmutaza u korteksu i strijatumu p<0.05, odnosno hipokampusu p<0.001; glutation reduktaza u kori mozga i strijatumu p<0.001, odnosno hipokampusu p<0.05; katalaza u korteksu p<0.001, odnosno

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“…Splitting at the dermoepidermal junction in epidermis, purulent exudate on surface with neutrophil infiltration, necrotic cells in epidermis (an arrow), epidermal necrosis and ulcer with fibrinopurulent exudate (indicated with a star), dermal collagen hyalinization, hemorrhage in dermis in 160 mg/kg/day agmatine group (hematoxylin and eosin stain x100) skin lesions were reported. 37,38 From the available evidence, it appears that oral and intraperitoneal administration of agmatine does not lead to a major toxicity in rodents and human beings.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous Toxicity of Agmatine in Rats

Uzbay¹,

Yertutanol²,

Mıdı³

et al. 2017

tjps

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ÖZAmaç: Bu çalışmanın amacı sıçanlarda ilk kez tekrarlayan agmatin uygulamasının sensorimotor kapılama sistemi üzerine etkilerini incelemekti, ancak subkütan uygulamada karşımıza çıkan beklenmedik ülseratif nekrotik lezyonlar bu konuya odaklanmamıza neden oldu. Gereç ve Yöntemler: İlk grup deneylerde, erkek Wistar albino sıçanlara 14 gün süreyle subkütan yoldan agmatin (40, 80 ve 160 mg/kg) veya salin (kontrol grubu) enjeksiyonu yapıldı (n=8 her bir grup). Uygulamaların üçüncü gününden itibaren agmatin verilen gruplarda ülseratif nekrotik deri lezyonları gözlendi. Bu etkilerin dermal bir reaksiyona bağlı olup olmadığını anlamak için ayrı bir denek grubuna aynı protokolle agmatin (80 mg/kg) intraperitoneal yoldan verildi (n=8 her bir grup). Bulgular: Bulgularımız subkütan yoldan verilen agmatinin geç dönemde ortaya çıkan bir dermal reaksiyona neden olurken, intraperitoneal uygulamanın böyle bir etki oluşturmadığına işaret etti. Lezyon gözlenen deneklerden alınan deri örneklerinin histopatolojik incelemesinde, enjeksiyon yerindeki deride aseptik nekroz saptanırken, bu deneklerin kan testleri normal bulundu. Sonuç: Bu bulgu sıçanlarda uzun süreli subkütan agmatin uygulamasının denek refahı bakımından risk oluşturan toksik bir etkiye neden olduğuna işaret etmektedir. Bu bulgu insanlarda oral yoldan reçetesiz olarak alınabilen agmatinin bazı potansiyel riskleri olabileceği konusunda sorular ortaya çıkarmaktadır. Anahtar kelimeler: Agmatin, deri reaksiyonu, subkütan yol, toksisite, sıçan Objectives: The aim of this study was to investigate the effects of repetitive agmatine administration on sensorimotor gating in rats first but, as unexpected, ulcerative necrotic cutaneous lesions appeared, thus, the study was directed primarily to clarify these results. Materials and Methods:In the first set of experiments, we administered agmatine (40, 80 and 160 mg/kg) and saline (control group) subcutaneously to male Wistar albino rats (n=8 for each group) for 14 consecutive days. Ulcerative necrotic cutaneous lesions appeared following the third day of agmatine administration. We decided to explore the potential toxic dermal effects of agmatine and conducted second set of experiments with two groups (n=8) to compare the effects of subcutaneous vs. intraperitoneal agmatine (80 mg/kg) injection to understand if the injection route determines the toxicity. Results: Our results showed that prolonged subcutaneous but not intraperitoneal administration of agmatine leads to a delayed dermal reaction in rats. Histopathologic examination of skin samples revealed cutaneous aseptic necrosis at the injection site whereas blood tests were found to be normal. Conclusion: This finding is important to point out the risks of prolonged subcutaneous administration of agmatine to rats within the concept of animal welfare. In addition, the results raise questions about the possible risks of over-the-counter use of agmatine among humans although the agent is taken via oral route.

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Effects of prolonged agmatine treatment in aged male Sprague–Dawley rats

Cited by 34 publications

References 63 publications

Protective effect of agmatine in acute chlorpromazine hepatotoxicity in rats

Protective effect of agmatine in acute chlorpromazine hepatotoxicity in rats

Agmatine prevents acute chlorpromazine-induced neurotoxicity in rats

Subcutaneous Toxicity of Agmatine in Rats

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