An inhibitor of aldose reductase and sorbitol accumulation from Anthocepharus chinensis.

A flavonoid glycoside was isolated from Anthocepharus chinensis. Its structure was elucidated by spectral data and determined to be myricetin 3-O-(4"-acetyl)-alpha-fucoside. This flavonoid glycoside and its aglycone showed potent inhibition against rat and porcine lens aldose reductase. The flavonoid aglycone also inhibited sorbitol accumulation in human red blood cells.

Neurochemical profile of effects of 28 neurotoxic chemicals on the central nervous system in rats (1). Effects of oral administration on brain contents of biogenic amines and metabolites.

We investigated the effects of oral administration of 28 organic chemical agents, all of which possess neurotoxicity and most of which are used as industrial solvents, on monoamine neurotransmitters and metabolites in the rat brain. Each chemical was administered to rats singly at a dose of one-quarter the LD50 value. Two hours after administration, acetylcholine, 3,4-dihydroxyphenylalanine (DOPA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin, and 5-hydroxyindoleacetic acid (5HIAA) contents in the small-brain regions were measured. Twenty-one of the 28 chemicals increased acetylcholine in the hippocampus, a ratio (21/28) far higher than the 0.5 expected were these chemicals to have no tendency to increase or decrease acetylcholine. This ratio was calculated for each brain substance. Large differences from 0.5 were also obtained for DOPAC (higher), and for 5HIAA and three neurotransmitters (dopamine, norepinephrine, and serotonin) in the hypothalamus (all lower). The ratios for MHPG and 5HIAA in the medulla oblongata were very high. In the hypothalamus, the concentrations of brain substances were easily altered by the test chemicals, and the turnover rates of hypothalamic norepinephrine and serotonin in the medulla oblongata seemed to be accelerated. Several lines of evidence obtained in previous studies suggest that the increased acetylcholine content in the brain homogenate induced by organic solvents such as toluene may be due to a decrease in acetylcholine release from nerve terminals. Based on the results of the present experiment and previous studies, this acetylcholine suppressing property appears to be common to solvents which possess anesthetic properties.

Behavioral evidence for modified receptor sensitivity in rat brain induced by methyl bromide exposure.

To clarify the neurochemical basis of methyl bromide toxicity in rats, we measured changes in the sensitivity of cerebral monoamine, dopamine (DA) and norepinephrine (NE) receptors, using abnormal behavior and locomotor activity as indicators of receptor sensitivity. Apomorphine and clonidine were used as specific agonists of DA (D1 and D2) and NE (alpha 2) receptors, respectively. In the first experiment, rats were exposed to methyl bromide gas at 25-200 ppm for 8hr once or to methyl bromide at 5-50 ppm 8hr a day for 7 days. The intensity of stereotyped oral (STO) behavior produced by an injection of apomorphine, 0.5 mg/kg i.p., was rated over the following 28 days. The STO behavior of rats exposed to methyl bromide (MB rats) was much more intense than in air-exposed (control) rats. This finding strongly suggests that the sensitivity of striatal DA, D1 and D2, receptors to apomorphine was increased by methyl bromide exposure. In the second experiment, rats were exposed to 50 ppm methyl bromide for 8hr once or to 10-50 ppm methyl bromide 8hr a day for 7 days. Seven days after the final exposure, rats were injected with a small dose of apomorphine, 0.3 mg/kg i.p., and the counts of apomorphine-induced locomotor activity (ALA) were recorded. The ALA counts of MB rats were markedly higher than in the control rats. This finding suggests that the DA receptors in the nucleus accumbens of MB rats are more sensitive to apomorphine than those of control rats. In the third experiment, rats were exposed to 50 ppm methyl bromide, 8hr a day for one day or 7 consecutive days, and the degree of attenuation of locomotor activity following clonidine injection (CLA) was rated. CLA counting was performed 7 days after the final exposure. CLA counts in MB rats were not attenuated as much as in the control rats. This indicates that the cerebral NE receptors, i.e., alpha 2-adrenoceptors, of MB rats may be less sensitive to clonidine than those of control rats. Increased behavioral sensitivity to apomorphine was observed in rats even when exposed to 5 ppm (TLV) methyl bromide.