Sustained increase of methylguanidine in rats after amygdala or hippocampal kindling

Shimizu, Yukito; Morimoto, Kiyoshi; Kuroda, Shigetoshi; Mori, Akitane

doi:10.1016/0920-1211(94)00004-g

Cited by 7 publications

(10 citation statements)

References 20 publications

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“…We also observed a two-to three-fold increase in GAA and MG levels in the cerebral cortex and hippocampus (2) months after ferric chloride injection into the sentory motor cortex, inducing an epileptic focus (14). Furthermore, GAA and MG levels in bilateral amygdala were shown to increase significantly in the amygdalaor hippocampal-kindled rat (15,16), an experimental model of epilepsy (17).…”

Section: Biochemistryond Molecular Biology Internationalmentioning

confidence: 73%

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Guanidino compounds generate reactive oxygen species

et al. 1996

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SUMMARYMethylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.

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Section: Biochemistryond Molecular Biology Internationalmentioning

confidence: 73%

“…Previously we observed that levels of GAA and MG markedly increase in the epileptogenic focus of the brain (5,14,15,16) and furthermore we have found that high brain levels of guanidino compounds are potent endogeneous convulsants when administrated by intracisternal injection (4, …”

Section: Discussionmentioning

confidence: 99%

Guanidino compounds generate reactive oxygen species

et al. 1996

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“…[1][2][3] Studies revealed that the liver and the kidneys oxidize CTN into creatol, which is converted into MG. [4][5][6][7] Oxidation of CTN with active oxygen (e.g., hydrogen peroxide) was proven to generate MG, whereas scavengers of active oxygen (e.g., glutathione, sorbitol) considerably reduced MG synthesis. 8 MG is expelled mainly from the kidney and is considered as not only a neurotoxin [9][10][11] but also a critical uremic toxin. Some experiments revealed that animals with high-level MG displayed a lot of functional and pathological characteristic features of uremia.…”

Section: Introductionmentioning

confidence: 99%

Methylguanidine cytotoxicity on HK-2 cells and protective effect of antioxidants against MG-induced apoptosis in renal proximal tubular cellsin vitro

et al. 2010

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The present study was designed to explore the toxic effect of MG on renal proximal tubular cells as well as the protective effect of antioxidants PGE1 and probucol against MG-induced apoptosis in renal proximal tubular cells. HK-2 cells were used as the subject. The cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. N-Acetyl-3-D-glucosaminidase (NAG) activity, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity were determined. Cell apoptosis was determined by flow cytometry (light scatter and propidium iodide/annexin V-FTC fluorescence) and by nuclear staining with Hoechst 33258. Cells were exposed to MG (0.25, 0.5, or 1 mmol/L), MG (0.5 mmol/L) + PGE1 (2 μg/L), and MG (0.5 mmol/L) + probucol (20 μmol/L) respectively for 24 h. MG induced a significant dose-dependent loss of cell viability. Both PGE1 and probucol improved the viability of MG-treated HK-2 cells. Cells showed apoptotic morphology (deepened stain, karyopyknosis, and apoptotic body) when exposed to 0.5 mmol/L MG for 24 h, and the apoptosis ratio was increased compared with the control. The presence of PGE1 or probucol significantly lowered the apoptotic ratio. Moreover, PGE1 or probucol notably decreased the MDA content and increased the SOD activity compared with when the cells were treated with MG only. The results of the present study clearly demonstrate that MG could promote apoptosis of renal proximal tubular cells in vitro. Both PGE1 and probucol could protect renal proximal tubular cells from MG-induced apoptosis.

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“…The level of MG extremely increases under the pathophysiological condition such as convulsion or chronic renal failure. For example, the levels of MG increased in the epileptogenic focus of the rat brain as experimental animals for epilepsy, i.e., the level of MG in amygdala showed significant increase in the epileptic animal models; amygdala-kindled rats [11,12]. The level of MG in the plasma increased several-fold under the uremic condition [3] when compared to the control.…”

Section: Discussionmentioning

confidence: 93%

“…Sustained increased level of MG was found in the brain of experimental models of epilepsy: amygrala-or hippocampus-kindled rats [11,12].…”

Section: Introductionmentioning

confidence: 96%

Inhibitory Effect of Antioxidants on Hydroxyl Radical Generation from Methylguanidine: An ESR Study

Noda

Mankura

2008

Neurochem Res

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Methylguanidine (MG) is known as not only a nephrotoxin but also as a neurotoxine. We have previously showed that MG itself generates hydroxyl radicals (*OH) in an in vitro study. In this study, we examined the inhibitory effects of ascorbate, EPC-K(1) (alpha-tocopheryl-L-ascorbate-2-O-phosphate diester), Trolox (water-soluble vitamin E analogue), and glutathione (GSH) on *OH generation from MG using an electron spin resonance (ESR) spectrometry with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). It was found that these compounds have potent inhibitory effect on *OH generation from MG in the order of ascorbate > GSH > EPC-K(1) > Trolox.

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Sustained increase of methylguanidine in rats after amygdala or hippocampal kindling

Cited by 7 publications

References 20 publications

Guanidino compounds generate reactive oxygen species

Guanidino compounds generate reactive oxygen species

Methylguanidine cytotoxicity on HK-2 cells and protective effect of antioxidants against MG-induced apoptosis in renal proximal tubular cellsin vitro

Inhibitory Effect of Antioxidants on Hydroxyl Radical Generation from Methylguanidine: An ESR Study

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