The anti-inflammatory effects of quinolinic acid in the rat.

Quinolinic acid (QUIN) levels are elevated in patients and animals suffering from chronic infectious diseases. In the present study, male Sprague-Dawley rats were used to test the anti-inflammatory effects of QUIN using the carrageenan (CGN)-induced paw edema assay and the CGN sponge assay. Results of these studies indicate that QUIN (30, 100 or 300 mg/kg i.p.) caused a reduction of carrageenan-induced inflammation by as much as 80% at the highest dose. Moreover, QUIN reduced exudate volume and inhibited leukocyte migration in the sponge granuloma assay. In another experiment, the anti-inflammatory activity of QUIN was eliminated in adrenalectomized rats. QUIN did not reduce edema caused by arachidonic acid, bradykinin or compound 48/80. Neither morphine nor naloxone altered the anti-inflammatory activity of QUIN. These results may suggest that QUIN exerts its anti-inflammatory activity through a direct action on neutrophils or vascular permeability.

Food constituents attenuate monoamine oxidase activity and peroxide levels in C6 astrocyte cells.

Glial cell monoamine oxidase (MAO) activity has been implicated as a contributor to oxidative neuronal damage associated with various neurodegenerative diseases. The attenuation of MAO activity may provide protection against oxidative neurodegeneration. In this investigation, the presence of MAO-B in rat C6 astrocyte cells was substantiated by dose-dependent inhibition of enzyme activity in the presence of chlorgyline-HCl and L-deprenyl. The present study evaluated various dietary-derived food constituents for evidence of inhibition on oxidative deamination of monoamines or peroxide radical trapping capacity. Results of this investigation indicate that compounds which inhibit C6 glial cell MAO enzyme activity or scavenge peroxide product include chlorogenic acid, (+)-catechin, taxifolin, (-)-epigallocatechin gallate (EGCG), fisetin, coenzyme Q0, curcumin, sesamol, morin, sesame oil, silymarin, green tea, ferulic acid, caffeic acid, and rutin hydrate. The results of this study indicate that dietary compounds can attenuate peroxide production in glial cells by either inhibiting the deamination of monoamines or acting as a free radical scavenger.

In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds.

Excessive nitric oxide (NO) production in the brain has been correlated with neurotoxicity and the pathogenesis of several neurodegenerative diseases. NO production from neuroglial cells surrounding neurons contributes significantly to the pathogenesis of these diseases. The suppression of NO production in these cells may be beneficial in retarding many of these disorders. The present study was designed to evaluate the capacity of dietary-derived polyphenolic compounds, flavonoids, crude extracts, oils, and other food constituents in suppressing the release of NO from lipopolysaccharide (LPS)/gamma-interferon (IFN-gamma) stimulated C6 astrocyte cells. In this experiment, 61 compounds were tested, and 36 showed significant suppressive effects of NO production. The results indicate that the following compounds exhibited a dose-dependent suppressive effect of NO production with an IC50 less than 10(-3) M: quercetin, (-)-epigallocatechin gallate, morin, curcumin, apigenin, sesamol, chlorogenic acid, fisetin, (+)-taxifolin, (+)-catechin, ellagic acid, and caffeic acid. Compounds, which reduce NO production at less than 300 ppm, include milk thistle, silymarin, grapenol, and green tea. These results demonstrate a possible value for dietary compounds to inhibit the excessive production of NO.

Gestational cocaine exposure alters postnatal pituitary-adrenal axis activity and stress endurance in rats.

Female pregnant Sprague-Dawley rats were injected once daily with 40 mg/kg cocaine hydrochloride or 0.9% saline from gestational day 12 (GD 12) to GD 21. From postnatal day 21 (PND 21) to PND 60, both male and female offspring were examined for stress response. Treated male and female offspring demonstrated a diminished tolerance to stress as determined by a cold water stress test performed at PND 21, 30 and 40. Base hormonal levels of adrenocorticotropin hormone (ACTH) and corticosterone were not affected by prenatal cocaine exposure in male offspring at PND 30. However, immobilization for 1 hr caused a significant sustained elevation of corticosterone levels at both PND 30 and PND 60 in male treated offspring as compared to the control group. Plasma ACTH levels were also significantly sustained after 1 hr of immobilization at PND 60 for the cocaine-treated male offspring. These results indicate both a diminished capacity to respond to stress and an abnormal heightened reactivity of the pituitary-adrenal axis in offspring exposed to cocaine in utero.

Repeated administration of cocaine alters dopamine uptake and release in the striatum nucleus accumbens.

Male Sprague-Dawley rats were administered 25 mg/kg, intraperitoneally (i.p.) cocaine-HCI twice daily for 14 consecutive days (total of 50 mg/kg), while control animals received an equivalent volume of 0.9% saline. After three days of withdrawal, the animals were sacrificed for dissection of striatal (STR) and nucleus accumbens (NA) brain regions. The treated group demonstrated a dose-dependent reduction for in vitro cocaine inhibition of [3H]dopamine (DA) uptake in the NA tissue verses controls. There were no significant differences amongst the treated and control groups for in vitro cocaine inhibition of [3H]DA in the STR. In vitro d-amphetamine (1, 5 and 10 microM)-stimulated DA release from STR tissue was not significantly different between the treated and the control groups. However, there was a significant decline in basal STR DA release and a significant enhancement of d-amphetamine (1 and 5 microM)-stimulated DA release in the NA for the treatment group versus controls. The results from the present study indicates sensitization to cocaine is primarily related to DA uptake and release in the NA.

The effect of selenium on the central dopaminergic system: a microdialysis study.

The effects of Selenium (Se) on central dopaminergic function were examined in male Sprague-Dawley rats. In this experiment, animals were implanted with microdialysis probes and dialysates were analyzed for dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). After reaching baseline values, sodium selenite was either injected intraperitoneally (i.p.) or directly infused into the striatum (ST) or nucleus accumbens (NA). Se administration of 3.0 mg/kg (i.p.) significantly increased (70%) DA overflow in the ST. Meanwhile direct Se perfusion (10 mM) also caused a significant elevation of synaptic DA concentrations in the ST and NA. Levels of DOPAC and HVA were minimally affected in all studies. In order to test for the effects of DA receptor activation, animals were pretreated with quinpirole (0.5 mg/kg, s.c.), an hour prior to Se (10 mM) infusion through the probe. It was found that quinpirole pre-treatment reduced Se-induced changes in DA concentrations. It was concluded from the present study that Se's central action might be related to its ability to potentiate DA function.