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PubMed1991

Stimulation of natural killer cell activity by murine retroviral infection and cocaine.

The effects of cocaine and murine AIDS on natural killer (NK) cell activity in C57BL/6 mice was studied. Cocaine may play a major role in the development and progression to AIDS in the human population. Chronic intraperitoneal injection of cocaine was shown to cause an increase in NK cell activity over those of saline-treated animals. Infection with LP-BM5 murine leukemia retrovirus was also shown to increase NK cell activity. NK cell activity was increased in retrovirally infected mice treated with cocaine beyond that of mice treated with cocaine alone. This study indicates an important immunomodulatory effect of cocaine on NK cell activity, especially when combined with the effects caused by retroviral infection.

Adjuvants, Immunologic↗
PubMed1991

Behavioral and metabolic interaction between gossypol and ethanol.

The effects of gossypol on ethanol-elicited responses pertaining to liver ethanol, acetaldehyde-metabolizing enzymes and alcohol preference were studied in rodents. Intraperitoneal injection of a single dose of gossypol, 100 mg/kg, inhibited hepatic alcohol dehydrogenase for 50 h in mice from both sexes. The acute gossypol treatment produced earlier inhibition of mouse liver cytoplasmic aldehyde dehydrogenase in male than female mice. Acute gossypol administration initially inhibited mouse liver subcellular mitochondrial aldehyde dehydrogenase in both sexes which was not evident 50 h later. Administration of gossypol, 10 mg/kg i.p., to male rats with preference for ethanol caused aversion for ethanol drinking. The enzymatic determinations indicate gender sensitivity of subcellular mouse liver aldehyde dehydrogenase to gossypol. The behavioral study suggests adverse metabolic interaction between gossypol and alcohol which may underlie the rat aversion to voluntary ethanol drinking.

Alcohol Dehydrogenase↗
PubMed1992

Nephrotoxic potential of N-(3,5-dichloro-4-hydroxyphenyl)succinimide and N-(3,5-dichloro-4-hydroxyphenyl)succinamic acid in Fischer-344 rats.

The ultimate nephrotoxicant species following administration of the agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) has yet to be determined. The purpose of this study was to examine the nephrotoxic potential of two potential metabolites of NDPS, N-(3,5-dichloro-4-hydroxyphenyl)-succinimide (NDHPS) and N-(3,5-dichloro-4-hydroxyphenyl)succinamic acid (NDHPSA). Male Fischer-344 rats (4 rats/group) were administered a single intraperitoneal injection of NDHPS or NDHPSA (0.2 or 0.4 mmol/kg) or vehicle and renal function was monitored at 24 and 48 h. Neither compound induced marked changes in renal function or morphology. These results suggest that NDHPS and NDHPSA do not contribute significantly to NDPS-induced nephrotoxicity.

Animals↗
PubMed1989

The ototoxic effect of cisplatin on guinea pigs in relation to dosage.

The effect on the electrophysiological hearing thresholds and the endocochlear DC potential (EP) was studied in four groups of guinea pigs receiving different doses of cisplatin. By multiple low-dose intraperitoneal injections a permanent hearing loss was produced without a permanent decrease of the EP. On the other hand, when cisplatin was given as a single high-dose intravenous injection, there was an impairment of the electrophysiological hearing thresholds and EP, depending upon the level of cisplatin dose. It is concluded that cisplatin-induced hearing loss is not necessarily a sequela to a loss of EP.

Animals↗
PubMed1993

Acute effects of cocaine on cochlear function.

The effects of a single administration of cocaine on the cochlea was evaluated by measuring amplitude-intensity functions of the N1 response of the auditory nerve. Amplitude-intensity functions of the N1 response to tone-pips of 500 Hz, 1, 2, 4 and 8 kHz were obtained before and after intraperitoneal injection of either saline, 3 mg/kg or 25 mg/kg of cocaine. N1 amplitudes were decreased after the administration of cocaine and this reduction was found to be dose dependent. The influence of cocaine on cochlear blood flow (CBF) was examined in order to test the possibility that cocaine induced reductions in CBF underlie these electro-physiological changes. Corresponding decreases in cochlear blood flow after cocaine exposure were observed.

Acoustic Stimulation↗
PubMed1994

Piribedil affects dopamine turnover in cochleas stimulated by white noise.

The presence of dopamine (DA) within the cochlea has been previously reported, indicating that its turnover increases under noise stimulation. In the present report, piribedil, a dopaminergic D2 agonist, was used in order to provide evidence of the activity of D2 receptors in the turnover of DA under noise stimulation. Long-Evans rats were intraperitoneally injected with distilled water or with a solution of piribedil one hour previously to either noise or silence exposure. Noise stimulation was performed in an anechoic chamber at 70, 90 or 110 dB SPL for one hour. The animals were then sacrificed and the cochlear contents of DA and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were quantified by HPLC with electrochemical detection. The administration of piribedil to animals kept in silence did not modify the cochlear DA, DOPAC and HVA content. Noise stimulation resulted in a decrease of the cochlear DA content and an increase of the cochlear DOPAC and HVA contents in vehicle treated animals. The administration of piribedil resulted in a blockade of this noise induced cochlear DA turnover. These results suggest that piribedil stimulates cochlear D2 receptors controlling the cochlear DA release. Piribedil action on D2 receptors could explain the improvement observed in some cochleo-vestibular diseases signs after piribedil treatment.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effect of cisplatin administration on the electrochemical composition of endolymph in the rat cochlea.

The effect of cisplatin on the electrochemical composition of the cochlear endolymph was studied in Long-Evans rats three days after a single intraperitoneal injection (8 mg/kg b.w.). A dose 2/3 of LD50 induced a decrease of the endolymphatic concentration of potassium whereas the endocochlear potential was unaffected. The discrepancy between these two findings indicated that cisplatin did not alter the mechanisms involved in the genesis of the endocochlear potential but modified the passive K transport into endolymph.

Analysis of Variance↗
PubMed1992

Effect of murine retroviral infection on hair and serum levels of cocaine and morphine.

LP-BM5 retrovirally infected female C57BL/6J mice were administered cocaine, morphine or both by daily intraperitoneal injection for 9 weeks. Drug concentrations were measured by radioimmunoassay in serum and in hair extracts. Hair samples obtained from all drug-treated mice were positive for the drug injected, while none of the saline-treated mice had detectable drug levels in hair or serum. The average morphine concentration obtained from non-infected mice was 11 ng/mg hair whereas the amount found in the LP-BM5-infected mice was significantly higher (20 ng/mg hair). Mice injected with both morphine and cocaine were given 50% of the regular dose of each drug and drug levels in the hair of these animals were approximately half that of mice injected with the full dose of the single drug. Non-infected mice treated with both drugs had a mean value of 7 ng morphine/mg hair and 374 ng cocaine/mg hair while retrovirus-infected mice had significantly higher concentrations, 10 ng morphine/mg hair and 1160 ng cocaine/mg hair (P less than 0.001). Serum concentrations of cocaine and morphine were significantly higher (P less than 0.01) in the retrovirus-infected animals from 40 min to 1.5 h. The increased concentrations of cocaine and morphine in serum during retrovirus infection are accompanied by a significant increase in the amount of drug incorporated into the hair matrix. This change indicates that retroviral infection may influence the disposition of these drugs in the systemic circulation.

Age Factors↗
PubMed1985

Quantitative studies of the effects of aging, meclofenoxate, and dihydroergotoxine on intraneuronal lipopigment accumulation in the rat.

Intraneuronal lipopigment accumulation is associated with ageing and certain diseases, and there are many claims that this can be influenced by drugs, particularly meclofenoxate (centrophenoxine). The various unsubstantiated or conflicting reports of the effects of this drug in animal studies indicate the need for methods for the demonstration of lipopigment accumulation in adequately defined, easily-identified, and relatively homogeneous neuronal populations; this study has validated two such methods by demonstrating significant differences between groups of rats at different ages in respect of measured lipopigment autofluorescence intensity from the most heavily pigmented regions of a subpopulation of Purkinje cells, and of the area overlying intraneuronal lipopigment in a region of the hippocampus. These methods were then used to investigate the effects of daily (5 days per week) intraperitoneal injections of meclofenoxate or dihydroergotoxine, over a period of 12 weeks, before sacrifice at 13.5 months. No significant effects of meclofenoxate were detected, but dihydroergotoxine administration was associated with a significant increase in mean area overlying intraneuronal lipopigment in the CA3a region of the hippocampus. The results do not confirm that meclofenoxate can induce a reduction in intraneuronal lipopigment, but suggest that chronic dihydroergotoxine administration was associated with an increase in intraneuronal volume of lipopigment in the cell bodies of CA3a hippocampal neurones.

Aging↗
PubMedDate not supplied

Sulphated cholecystokinin octapeptide inhibits ethanol consumption in the rat.

Twenty-three hr water deprived rats received access to 5% ethanol solution for 30 min daily. Intraperitoneal injection of sulphated cholecystokinin octapeptide (CCK-8, 2.0-16.0 micrograms/kg) significantly inhibited ethanol consumption, but injection of desulphated CCK-8 did not affect ethanol consumption. These results confirm a previous report that CCK-8 suppresses ethanol intake, and indicate that inhibition of ethanol consumption by CCK-8 depends on sulphation of its tyrosyl residue. This chemical specificity of action of CCK-8 is also characteristic of other known behavioral and physiological effects of peripherally-administered cholecystokinin-like peptides.

Alcohol Drinking↗
PubMedDate not supplied

The effects of oral and intraperitoneal administration of ethanol on the activities of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rats.

The activities of hepatic glucose-6-phosphate and 6-phosphogluconate dehydrogenases decreased significantly only in male rats, when rats of both sexes were fed a 2% sucrose solution containing 25% ethanol for six weeks. Sucrose (2%) activation of these enzymes was significant only in female rats. The daily administration of ethanol (5 g/kg body wt.) by intraperitoneal injection for two weeks significantly decreased the activities of these enzymes and eliminated the sex differences in the response to ethanol ingestion.

Administration, Oral↗
PubMed1987

Development of inflammation and augmented chemotactic responsiveness of murine peritoneal macrophages following treatment with Entamoeba histolytica trophozoites.

The accumulation of inflammatory cells in the peritoneal cavity of C57BL/6 mice was examined following intraperitoneal injection of Entamoeba histolytica trophozoites. Two different strains of E. histolytica were used: a virulent strain (IP:0682:1) and a non-virulent strain (DKB). Injection of 10(6) trophozoites of either strain resulted in significant increases in the numbers of total peritoneal cells, macrophages and polymorphonuclear cells as compared to either saline-injected control mice or mice injected with 10-fold lower doses of trophozoites. The in vitro chemotactic response of macrophages from amoebae-induced exudates was also examined. Macrophages from mice treated with strain IP:0682:1 or DKB strain trophozoites were more responsive to complement-derived chemotactic factors than macrophages from saline-injected mice. This increase was significant on day 2 and persisted at enhanced levels until day 20 when the experiment was terminated. In addition, it was found that trophozoites activated normal mouse serum resulting in the production of serum-derived chemotactic activity.

Amebiasis↗
PubMed1996

Ontogenetic development of the locomotor response to levodopa in the rat.

Administration of exogenous levedopa triggers locomotion in young rats prior to the onset of quadripedal movement. The same substance decreases locomotion in adult animals. The ontogenetic development of the response to levodopa was investigated in rats. Intraperitoneal injection of levodopa (150 micrograms/kg body weight) caused characteristic "crawling" or "swimming-like" locomotion patterns in 5- to 6-day-old animals. Noradrenergic mechanisms may be involved in this behavior. In 18- to 20-day-old rats, levodopa caused excessive locomotor activity, including running, jumping, and wall climbing. This effect can be attributed to the activation of postsynaptic dopaminergic receptors that are already present during the early stages of life. At 25-30 days of age, levodopa-induced motor activity was decreased in comparison with that of the 18- to 20-day-old rats, possibly due to changing patterns of D1/D2-dopamine receptor subtype interactions. In contrast to observations in younger rats, the same dose of levodopa suppressed motor activity in 60- to 75-day-old rats. The presence of functional dopamine autoreceptors at this age may account for the change.

Aging↗
PubMedDate not supplied

Gender differences in the mechanism of dioxin toxicity in rodents and in nonhuman primates.

This study examined the differences in mechanisms of toxicity when adipose cells from males and females were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Glucose uptake by adipose tissue in vitro was decreased significantly in male guinea pigs within 1 d of intraperitoneal injection of TCDD, but there was no significant effect in females, even at 28 d after treatment. A similar difference between male and female guinea pigs was detected in the effect of TCDD on lipoprotein lipase (LPL) activity, except that a significant decrease in LPL activity was observed 28 d after treatment. Experiments with adipose tissue explants from untreated guinea pigs and macaques revealed similar gender differences in the effect of TCDD in vitro on glucose uptake and LPL activity. Both time-course studies and dose-response studies with TCDD in vitro confirmed the greater sensitivity of male tissues to TCDD toxicity. TCDD induced lipid peroxidation in the adipose tissues of male guinea pigs, while it had no effect in females. 3H-TCDD binding affinity studies in adipose explant tissues showed that tissues from male guinea pigs and monkeys had a higher binding capacity for TCDD than female tissues. TCDD induced a significant reduction in nuclear protein phosphorylation and an increase in cytosolic protein phosphorylation in adipose tissue from male guinea pigs; the effects in female tissues were opposite: nuclear protein phosphorylation increased and cytosolic protein phosphorylation decreased. In a cell-free system in the absence of the nucleus, adipose tissues from male guinea pigs and monkeys responded to TCDD with a rapid stimulation of tyrosine kinase activity but female tissues from both species had a significantly lower and slower response. TCDD induced the DNA binding of AP-1 in adipose tissues of male guinea pigs, but in female tissues TCDD reduced the DNA binding of AP-1. In summary, the results of this study demonstrate gender differences in the response of nonreproductive cells to TCDD. Some of these differences involve different mechanisms of toxicity in both the cytoplasmic and nuclear compartments of the cell.

Adipose Tissue↗
PubMed1994

In vivo binding of [125I]NH2-carfentanil to mu opioid receptors in mouse brain.

A functionalized derivative of the mu opioid agonist carfentanil was synthesized (NH2-carfentanil) and showed high specific activity when radiolabeled with iodine. [127I]NH2-carfentanil displayed high affinity and pronounced mu-binding selectivity with a delta/mu selectivity ratio of over 1200. The ability of [125I]NH2-carfentanil to interact in vivo with opioid receptors was determined in mouse brain using ex vivo binding techniques. Twenty minutes after intraperitoneal injection, 0.1% of the [125I]NH2-carfentanil injected into the mouse was present in the brain. [125I]NH2-carfentanil specific binding was inhibited by co-injection of naloxone or morphine while naltrindole, a delta-selective antagonist, was unable to displace the bound radioligand. Autoradiographic experiments revealed a heterogeneous distribution of [125I]NH2-carfentanil specific binding sites, maximal binding occurred in areas with high densities of mu receptors. Peripherally administered iodo-NH2-carfentanil selectively labelled central mu opioid receptors in mouse indicating great potential for single photon emission computed tomography studies.

Animals↗
PubMed1996

Effects of calcitonin and parathyroid hormone on the distribution of F-actin in the clear zone of osteoclasts in vivo.

To elucidate the relation between the distribution of F-actin bands in the clear zone and the bone-resorbing activity of osteoclasts in vivo, the endocranial surfaces of calvariae from 7-day-old Wistar rats were stained with F-actin-specific fluorescein isothiocyanate-labeled phalloidin (FITC-phalloidin) with and without the intraperitoneal injection of the calcium-regulating hormones, calcitonin (CT), and parathyroid hormone (PTH). Some specimens were double-stained with FITC-phalloidin and a monoclonal antibody, ED1, which stained monocytes and macrophages. In normal rats, almost 80% of the osteoclasts showed ring-shaped F-actin bands in the clear zone, and the remaining 20% showed arch- or line-shaped F-actin bands. From 15 min to 1 h after the injection of CT (salmon, 10 mg/kg), the number of osteoclasts with ring-shaped F-actin bands decreased significantly. At 1 h, few F-actin bands were detected in osteoclasts, which were still stained by ED1. However, these F-actin bands recovered to the normal level at 6 h. On the other hand, from 15 min to 6 h after the injection of PTH (bovine, 50 mg/kg), the number of osteoclasts with arch- or line-shaped F-actin bands decreased significantly. These results indicate that osteoclasts with arch- or line-shaped F-actin bands in the clear zone had lower bone-resorbing activity than those with ring-shaped F-actin bands, and that the formation of bands could be controlled by calcium-regulating hormones over the course of a few hours. Observation of the endocranial surfaces of calvariae might be useful for examining factors which affect the activities of osteoclasts in vivo.

Actins↗
PubMed2005

Ethanol administration results in a prolonged decrease in blood ionized calcium levels in the rat.

Previous studies have shown that ethanol decreases the level of ionized calcium (iCa) in the blood, and appears to prevent a compensatory increase in parathyroid hormone level. We have shown, however, that the presence of ethanol interferes with the measurement of blood iCa by the most commonly used iCa analyzer. It is impossible to interpret ethanol-induced alterations in Ca-regulating hormone levels without accurate measurement of blood iCa, thus the purpose of this study was to determine if ethanol decreases blood iCa levels independent of methodological artifacts. The time course of ethanol's effect and the relationship between iCa and blood ethanol concentration (BEC) were also examined. Rats (n=22) received ethanol (1.5 or 3 g/kg body weight) or saline by intraperitoneal injection. Blood samples were obtained by tail nick at 0, 2, 6, 24, 48 h and 8 days postinjection, and analyzed for iCa, pH, and BEC. Blood iCa and pH were measured using the I-Stat Clinical Analyzer, whose performance is not affected by the presence of ethanol. Ethanol administration resulted in a decrease in blood iCa levels. The magnitude and time course of the decrease varied with dose of ethanol, being greater and more prolonged with the higher dose, and blood iCa levels were not fully recovered at 48 h postinjection. No significant relationship was found between individual iCa and BEC values. This study confirms that ethanol decreases blood iCa levels, independent of methodological artifacts. Prolonged disruptions in Ca homeostasis resulting from ethanol consumption could have implications for long-term bone health.

Alcohol Drinking↗
PubMed2004

Tetrahydrobiopterin biosynthesis in white and brown adipose tissues is enhanced following intraperitoneal administration of bacterial lipopolysaccharide.

Tetrahydrobiopterin is an essential cofactor for nitric oxide synthase (NOS). This study was undertaken to examine the effects of intraperitoneally injected lipopolysaccharide on tetrahydrobiopterin biosynthesis in murine white and brown adipose tissues. Tetrahydrobiopterin content, catalytic activity and mRNA expression level of GTP cyclohydrolase I (GCH), rate-controlling enzyme in de novo biosynthesis of tetrahydrobiopterin, in both adipose tissues were up-regulated by 500-microg lipopolysaccharide at 6 h after the injection. On the contrary, treatment of 3T3-L1 adipocytes with lipopolysaccharide alone did not affect GCH mRNA expression level, whereas the combination of lipopolysaccharide, tumor necrosis factor (TNF)-alpha, and interferon gamma induced the increase in expression levels of GCH mRNA and CD14 mRNA. Collectively, our results showed that tetrahydrobiopterin biosynthesis can be augmented by increased GCH activity caused by a synergistic effect of lipopolysaccharide and cytokines in white and brown adipose tissues. These observations support the view that tetrahydrobiopterin biosynthesis in the adipose tissues is a target of inflammatory events triggered by peripheral LPS injection.

3T3-L1 Cells↗