Effect of aristolochic acid on arachidonic acid cascade and in vivo models of inflammation

Moreno, Juan J.

doi:10.1016/0162-3109(93)90061-t

Cited by 45 publications

(21 citation statements)

References 15 publications

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“…Quantitation of slice fluorescence in Figure 3B showed that robust neurodegeneration due to binge ethanol was almost completely abolished by manoalide (suppressed relative to Mano alone), indicating that sPLA2 activity has an important role. However, as shown in Figure 3C, aristolochic acid (ATA, 10 µM), an inhibitor of groups I+IIA-B sPLA2 isoforms (Moreno, 1993), was ineffective, suggesting that sPLA2 activities in groups other than I and IIA-B are responsible in these developing brain slice cultures.…”

Section: Resultsmentioning

confidence: 98%

Phospholipase A2, Oxidative Stress, and Neurodegeneration in Binge Ethanol-Treated Organotypic Slice Cultures of Developing Rat Brain

Moon

Tajuddin

Brown

et al. 2013

Alcohol Clin Exp Res

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Background Brain neurodamage from chronic binge ethanol exposure is linked to neuroinflammation and associated oxidative stress. Using rat organotypic hippocampal-entorhinal cortical (HEC) slice cultures of developing brain age, we reported that binge ethanol promotes release of a neuroinflammatory instigator, arachidonic acid (AA), concomitant with neurodegeneration, and that mepacrine, a global inhibitor of phospholipase A2 (PLA2) enzymes mobilizing AA from phospholipids, is neuroprotective. Here we sought with binge ethanol-treated HEC cultures to establish that PLA2 activity is responsible in part for significant oxidative stress, and to ascertain the PLA2 families responsible for AA release and neurodegeneration. Methods HEC slices, prepared from one wk-old rats and cultured 2–2½ wks, were exposed to 100 mM ethanol over 6 successive days, with 4 daytime “withdrawals” (no ethanol). Brain 3-nitrotyrosinated (3-NT) and 4-hydroxynonenal (4-HNE)-adducted proteins, oxidative stress footprints, were immunoassayed on days 3 through 6, and mepacrine’s effect was determined on day 6. The effects of specific PLA2 inhibitors on neurodegeneration (propidium iodide staining) and AA release (ELISA levels in media) in the cultures were then determined. Also, the effect of JZL184, an inhibitor of monoacylglycerol lipase (MAGL) which is reported to mobilize AA from endocannabinoids during neuroinflammatory insults, was examined. Results 3-NT- and 4-HNE-adducted proteins were significantly increased by the binge ethanol exposure, consistent with oxidative stress, and mepacrine prevented the increases. The PLA2 inhibitor results implicated secretory PLA2 (GII sPLA2) and to some extent Ca+2-independent PLA2 (GVI iPLA2) in binge ethanol-induced neurotoxicity and in AA release, but surprisingly, Ca+2-dependent PLA2 (GIV cPLA2) did not appear important. Furthermore, unlike PLA2 inhibition, MAGL inhibition failed to prevent the neurodegeneration. Conclusions In these developing HEC slice cultures, pro-oxidative signaling via sPLA2 and iPLA2, but not necessarily cPLA2 or MAGL, is involved in ethanol neurotoxicity. This study provides further insights into neuroinflammatory phospholipase signaling and oxidative stress underlying binge ethanol-induced neurodegeneration in developing (adolescent-age) brain in vitro.

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Section: Resultsmentioning

confidence: 98%

Phospholipase A2, Oxidative Stress, and Neurodegeneration in Binge Ethanol-Treated Organotypic Slice Cultures of Developing Rat Brain

Moon

Tajuddin

Brown

et al. 2013

Alcohol Clin Exp Res

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“…Several authors studied the anti-inflammatory activity of aristolochic acid and to investigate the effect of the alkaloid on the enzymes involved in the release of eicosanoids. Results demonstrated that aristolochic acid was inhibited the inflammation induced by immunological, immune complexes, and non-immunological agents such as carrageenan or croton oil [51]. …”

Section: Introductionmentioning

confidence: 99%

Therapeutic application of natural inhibitors against snake venom phospholipase A2

Samy¹,

Gopalakrishnakone²,

Chow³

2012

Bioinformation

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Natural inhibitors occupy an important place in the potential to neutralize the toxic effects caused by snake venom proteins and enzymes. It has been well recognized for several years that animal sera, some of the plant and marine extracts are the most potent in neutralizing snake venom phospholipase A2 (svPLA2). The implication of this review to update the latest research work which has been accomplished with svPLA2 inhibitors from various natural sources like animal, marine organisms presents a compilation of research in this field over the past decade and revisiting the previous research report including those found in plants. In addition to that the bioactive compounds/inhibitor molecules from diverse sources like aristolochic alkaloid, flavonoids and neoflavonoids from plants, hydrocarbones 2, 4 dimethyl hexane, 2 methylnonane, and 2, 6 dimethyl heptane obtained from traditional medicinal plants Tragia involucrata (Euphorbiaceae) member of natural products involved for the inhibitory potential of phospholipase A2 (PLA2) enzymes in vitro and also decrease both oedema induced by snake venom as well as human synovial fluid PLA2. Besides marine natural products that inhibit PLA2 are manoalide and its derivatives such as scalaradial and related compounds, pseudopterosins and vidalols, tetracylne from synthetic chemicals etc. There is an overview of the role of PLA2 in inflammation that provides a rationale for seeking inhibitors of PLA2 as anti-inflammatory agents. However, more studies should be considered to evaluate antivenom efficiency of sera and other agents against a variety of snake venoms found in various parts of the world. The implications of these new groups of svPLA2 toxin inhibitors in the context of our current understanding of snake biology as well as in the development of new novel antivenoms therapeutics agents in the efficient treatment of snake envenomations are discussed.

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“…In traditional Chinese medicine literature, 'GuanMu Tong' is mentioned to ''clear heart fire, promote diuresis, restore menstruation and increase milk secretion'' [1]. Aristolochic acid (AA) is the active ingredient of this product and is said to be useful in treating infections, arthritis, gout and tumors [2][3][4]. However, recent studies have confirmed that the main culprit leading to renal injury is the same aristolochic acid found in many Chinese herbal preparations.…”

Section: Introductionmentioning

confidence: 99%

Fatal renal failure due to the Chinese herb “GuanMu Tong” (Aristolochia manshuriensis): Autopsy findings and review of literature

Zhu

Ananda

Ruxia

et al. 2010

Forensic Science International

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Effect of aristolochic acid on arachidonic acid cascade and in vivo models of inflammation

Cited by 45 publications

References 15 publications

Phospholipase A2, Oxidative Stress, and Neurodegeneration in Binge Ethanol-Treated Organotypic Slice Cultures of Developing Rat Brain

Phospholipase A2, Oxidative Stress, and Neurodegeneration in Binge Ethanol-Treated Organotypic Slice Cultures of Developing Rat Brain

Therapeutic application of natural inhibitors against snake venom phospholipase A2

Fatal renal failure due to the Chinese herb “GuanMu Tong” (Aristolochia manshuriensis): Autopsy findings and review of literature

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