Quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer

doi:10.1016/S0009-2797(99)00080-0

Chemico-Biological Interactions

Volume 118, Issue 3, 15 April 1999, Pages 201-215

https://doi.org/10.1016/S0009-2797(99)00080-0 Get rights and content

Abstract

Quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhanced the Fenton reaction in phosphate buffer, respectively. The enhancement by quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid of the Fenton reaction may be partly related to their respective actions in the biological systems such as a neurotoxic effect (quinolinic acid), a marked growth-inhibitory action on rice seeding (α-picolinic acid and fusaric acid), and an antiseptic (2,6-pyridinedicarboxylic acid). The ultraviolet–visible absorption spectrum of the mixture of α-picolinic acid with ferrous ion showed a characteristic visible absorbance band with a λ_max at 443 nm, suggesting that α-picolinic acid chelate of Fe²⁺ ion forms in the solution. Similar characteristic visible absorbance band was also observed for the mixture of Fe²⁺ ion with quinolinic acid (or fusaric acid, or 2,6-pyridinedicarboxylic acid). The chelation seems to be related to the enhancement by quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid of the Fenton reaction. α-Picolinic acid was reported to be a toxic substance isolated from the culture liquids of blast mould (Piricularia oryzae CAVARA). On the other hand, it has also been known that chlorogenic acid protects rice plants from the blast disease. The chlorogenic acid inhibited the formation of the hydroxyl radical in the reaction mixture of α-picolinic acid, FeSO₄(NH₄)₂SO₄, and H₂O₂. Thus the inhibition may be a possible mechanism of the protective action of the chlorogenic acid against the blast disease.

Introduction

Quinolinic acid (2,3-pyridinedicarboxylic acid) is a tryptophan metabolite of the kynurenine pathway. It is a potent excitant of neurones in the rat brain and acts preferentially on N-methyl-d-aspartate receptor [1]. Intracerebral injection of quinolinic acid reproduces the pathological features of Huntington’s disease such as γ-aminobutyric acid depletion and striatal spiny cell loss [2], [3].

On the other hand, quinolinic acid seems to play an important role in neurodegenerative inflammatory and infectious diseases. Markedly increased concentrations of quinolinic acid were found in both lumbar cerebrospinal fluid and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases, and septicaemia) [4]. Heyes et al. reported the significant correlations between the magnitude of the increases in cerebrospinal fluid quinolinic acid and the degree of neuropsychological deficits in HIV-infected patients [5]. The delayed increases in the levels of the N-methyl-d-aspartate receptor agonist, quinolinic acid also occur in brain following transient ischemia in the gerbil [6].

The mechanism by which quinolinic acid exerts its neurotoxic effects has been ascribed to its ability to induce excessive activation of N-methyl-d-aspartate receptors, calcium channels opening and consequent massive calcium entry into the cell [7]. In addition to these mechanism, Rios and Santamaria have reported the involvement of lipid peroxidation and oxidative stress in the quinolinic acid-induced lesions [8], [9]. Furthermore, Shoham et al. have shown that after single unilateral injections of quinolinic acid into the rat ventral-striatal region, irons accumulate in high concentrations in basal ganglia area such as globus pallidus and substantia nigra pars reticulata [10]. Thus, the relationship among the iron ions, quinolinic acid, and the lipid peroxidation should be clarified.

On the other hand, α-picolinic acid (2-pyridinecarboxylic acid) was isolated from the culture liquids of blast mould (Piricularia oryzae CAVARA) as a toxic substance, possessing a marked growth-inhibitory action on rice seeding [11]. α-Picolinic acid was proved to be contained in the rice plant attacked with blast disease [12]. Fusaric acid (5-butylpicolinic acid) which was isolated from culture liquids of Gibberella fujikuroi Wr., the causative mold of the ‘BAKANAE’ disease of rice plants also showed similar toxic effects on rice seeding as α-picolinic acid did [13]. 2,6-Pyridinedicarboxylic acid is an antiseptic which is produced by Bacillus subtilis.

In this paper, we conduct experiments to clarify the effects of quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid on the hydroxyl radical formation, focusing the interaction between these compounds and iron ions. Since quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid have a common chemical structure, i.e. 2-pyridinecarboxylic acid moiety, various 2-pyridinecarboxylic acid-derived compounds are also examined to clarify the structure/activity relationships.

It has been known that chlorogenic acid protects rice plants from the deleterious effect by α-picolinic acid produced during the blast disease [12]. In order to know the mechanism of the resistance of chlorogenic acid, the effects of chlorogenic acid on the formation of the hydroxyl radical are also investigated in the reaction mixture containing α-picolinic acid, FeSO₄(NH₄)₂SO₄, H₂O₂, and chlorogenic acid.

Furthermore, the effects of the anions such as the phosphate ions and carbonate ions on the hydroxyl radical formation are also examined, using a phosphate buffer system and a carbonate buffer system as the reaction solvent. We choose the two anions because phosphate ions is the primary intracellular anions (37.5 mM) and carbonate ions are abundant anions in the extracelluar fluid (30 mM).

Section snippets

Materials

Quinolinic acid (2,3-pyridinedicarboxylic acid) and kynurenic acid were purchased from Nacalai Tesque (Kyoto, Japan). Phthalic acid, benzoic acid, 4-pyridinecarboxylic acid, α-picolinic acid (2-pyridinecarboxylic acid), nicotinic acid (3-pyridinecarboxylic acid), 2,6-pyridinedicarboxylic acid, 4-hydroxypyridine, and 2-quinolinecarboxylic acid were from Wako Pure Chemical Industries (Osaka, Japan). Ferrous ammonium sulfate was obtained from Kishida (Osaka, Japan). 5,5-Dimethyl-1-pyrroline N

Enhancement by α-picolinic acid and its related compounds of hydroxyl radical formation

In order to know the effect of the α-picolinic acid on the hydroxyl radical formation (Fig. 1), an ESR spectrum of the complete reaction mixture containing α-picolinic acid, hydrogen peroxide, ferrous ammonium sulfate, and DMPO in sodium phosphate buffer (pH 7.4) was measured (Fig. 2). The typical 1:2:2:1 ESR spectrum (a_N=1.49 mT, a_H=1.49 mT) of the DMPO/OH radical adducts was observed for the complete reaction mixture (Fig. 2(A)) [15]. Although the ESR spectrum was also detected when

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^☆: This study was performed through Special Coordination Funds for Promoting Science and Technlogy of the Science and Technology Agency of the Japanese Government.

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Quinolinic acid, α-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer☆

Abstract

Introduction

Section snippets

Materials

Enhancement by α-picolinic acid and its related compounds of hydroxyl radical formation

Eur. J. Pharmacol.

Neurosci. Lett.

Exp. Neurol.

Biochem. Biophys. Res. Commun.

Arch. Biochem. Biophys.

Brain Res.

Arch. Biochem. Biophys.

Biochem. Pharmacol.

Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain

Science

Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid

Nature