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. 2017 Aug;14(2):127-133.
doi: 10.4274/tjps.85057. Epub 2017 Aug 15.

Subcutaneous Toxicity of Agmatine in Rats

Tayfun Uzbay  1 , Fatma Duygu Kaya Yertutanol  1 , Ahmet Midi  2 , Burcu Çevreli  1
Affiliations

Subcutaneous Toxicity of Agmatine in Rats

Tayfun Uzbay et al. Turk J Pharm Sci. 2017 Aug.

Abstract

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.

Keywords: Agmatine; rat; skin reaction; subcutaneous route; toxicity.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
A lesion at the back skin of a subject in group 5
Figure 2
Figure 2
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)
See this image and copyright information in PMC

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