Effects of Propofol on the Liver Oxidative-Antioxidant Balance in a Rat Model of Parkinson's Disease.

BACKGROUND: Parkinson's disease is caused by the destruction of dopaminergic neurons in the substantia nigra of the midbrain. One of the possible factors involved in the pathogenesis of Parkinson's disease is impaired oxidativeantioxidative balance. OBJECTIVES: The present study aimed to evaluate selected parameters of the liver oxidative-antioxidative system in a Wistar rat model with Parkinson's disease treated with propofol. MATERIAL AND METHODS: Experiments were performed on 32 rats divided into 4 groups: 1 - control, 2 - Parkinson's disease, 3 - control with propofol, 4 - Parkinson's disease with propofol. The rats were decapitated at 8 weeks of age and their livers were collected. In the liver, the activities of catalase (CAT), glutathione peroxidase (GPx), glutathione transferase (GST), glutathione reductase (GR) and the concentrations of: Malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS) were assessed. RESULTS: The study demonstrated a decrease in CAT activity and an increase in MDA, TOS concentrations in group 2 compared to that of group 1. Administration of propofol in rats of group 4 caused an increase in CAT activity and a decrease in MDA concentration compared to that of group 2 and an increase in TAC, CAT, GR levels, decrease in MDA levels compared to that of group 1. There was also an increase in GR and TAC in group 3 compared to that of group 1. CONCLUSIONS: Propofol in Parkinson's disease stimulates the production of antioxidant enzymes in the liver, simultaneously decreasing oxidative stress, which has a beneficial effect on the oxidative-antioxidative balance.

Evaluation of the analgesic effect of morphine on models of acute nociceptive pain in rats with a central noradrenergic system lesion.

OBJECTIVES: Stimulation of some noradrenergic system receptors demonstrates a synergistic anti-nociceptive effect with the opioid system at the level of peripheral tissues, spinal cord, and supraspinal structures. Furthermore, opioids stimulate the noradrenergic descending pathways originating from the substantia nigra by presynaptic inhibition of the GABA neuron ends. It is thus important to determine whether a disruption to the adrenergic transmission obtained via DPS-4 administration to neonatal rats impacts the perception of noxious stimuli mediated by 5-HT3-serotonin receptors at the level of spinal cords or higher tiers of the central nervous system. DESIGN & SETTING: The studies were conducted with neonatal and adult rats, males of the Wistar strain in which a central noradrenergic system lesion was induced with DSP-4 on days 1 and 3 of life. Next, the evaluation of the analgesic effect of morphine was performed on 8- to 10-week-old animals using the following models of acute nociceptive pain: the hot plate test and the tail immersion test as models of acute nociceptive pain induced by a thermal stimulus, and the paw withdrawal test as a model of nociceptive pain caused by a mechanical stimulus. RESULTS: Morphine was found to produce a longer-lasting analgesic effect in the tail immersion test in the control group than in rats. Similarly, in the paw withdrawal test, this substance generated a strong analgesic effect (with over 200% of analgesia) in the control group, whereas its action in the rats with DSP-4 lesions was statistically significant. Morphine induced analgesia at about 13-14% in the control rats when examined with the hot plate test. CONCLUSIONS: The disruption to the central noradrenergic system in an early stage of development resulted in a reduction of the analgesic effect of morphine in the models of acute pain in which the mechanisms of supraspinal perception are involved.

Impairment in Pain Perception in Adult Rats Lesioned as Neonates with 5.7-Dihydroxytryptamine.

BACKGROUND: Whereas some studies have demonstrated the essential role of 5-hydroxytryptamine (5-HT) in tramadol and acetaminophen analgesia, other research has presented conflicting results. To dispel doubts, some aspects of the involvement of 5-HT in the antinociceptive properties of these drugs remain to be clarified. OBJECTIVES: The aim of this study was to determine whether the serotoninergic system dysfunction produced by neonatal 5-HT lesion in rats may affect the antinociceptive effects of tramadol and acetaminophen administered in adulthood. MATERIAL AND METHODS: Three days after birth, the control rats were pretreated with desipramine HCl (20 mg/kg i.p.) 30 min before intraventricular saline--vehicle injection. A separate group received 5.7-DHT; 2×35 µg in each lateral ventricle. At the age of 8 weeks, 5-HT and 5-hydroxyidoleaceticacid (5-HIAA) concentrations were determined in the thalamus and spinal cord by an HPLC/ED method. The antinociceptive effects of tramadol (20 mg/kg i.p.) or acetaminophen (100 mg/kg i.p.) were evaluated by a battery of tests. RESULTS: 5.7-DHT lesioning was associated with a reduction in 5-HT and 5-HIAA content of the thalamus (>85% and >90%) and spinal cord (>58% and 70%). Neonatal 5.7-DHT treatment produced a significant reduction in the antinociceptive effect of tramadol in the hot plate, tail-immersion, paw withdrawal and writhing tests. In the formalin hind paw test, the results were ambiguous. 5-HT lesion was also associated with a decrease in the analgesic effect of acetaminophen in the hot plate and writhing tests. A similar relationship wasn't found in the other assessments conducted with the use of acetaminophen. CONCLUSIONS: The present study provides evidence that (1) an intact serotoninergic system is required for the adequate antinociceptive action of tramadol, and (2) the serotoninergic system exerts a negligible influence on acetaminophen-induced analgesia in rats. We hypothesize that similar abnormalities in nociception may occur in patients with 5-HT dysfunction (e.g. depression), so these results should be complied in analgesic dosage adjustment.