PubMed Health⌕ Search

Biomedical subjects

F S Messiha

Publications and source records attributed to F S Messiha.

At least 91 records · Page 5Linked to original sources
PubMed1982

The effect of oral contraceptives on reproductive function during semichronic exposure to ethanol by the female rat.

1. Female rats were placed on water, 5% ethanol (ET), or 20% ET drinking solutions for 8 weeks. The last 2 weeks, the rats received orally either ethinyl estradiol (EE), norethindrone acetete (NED), or a combination of both. 2. Luteinizing hormone decreased due to ET drinking and was undetectable subsequent to the steroidal treatment. 3. Prolactin increased after steroid treatment and alcohol drinking in the controls. 4. Ethanol (5%) plus EE increased prolactin as did the steroidal combination, whereas ET (20%) likewise increased prolactin in conjunction with NED over water controls. 5. Hepatic alcohol dehydrogenase was inhibited due to EE when compared to water-controls in the 5% ET drinking animal, whereas aldehyde dehydrogenase was induced in combination with NED in both the 5% and 20% ET drinking rats.

Alcohol Oxidoreductases↗
PubMed1982

Modulation of rat testicular alcohol dehydrogenase by psychoactive agents.

The in vivo and in vitro effect of selected psychoactive agents on specific activity of rat testicular alcohol dehydrogenase (T-ADH) was studied. Drinking of 15% ethanol solution for 14 consecutive days inhibited endogenous T-ADH from controls. This inhibition was enhanced when the animals were kept in complete darkness. Short-term administration of drugs with various pharmacologic properties, i.e. CNS-stimulants, a muscle relaxant, an antidepressant and estrogenic steroids, exerted little effect on T-ADH. d-Amphetamine, 3-methoxytyramine (3MT) and histamine inhibited-T-ADH in vitro. The amphetamine inhibition was non-competitive and the KI50 determined was of moderate magnitude.

Alcohol Oxidoreductases↗
PubMed1982

Ethanol and hypobarometric simulated high altitude: a gonadal-hepatic toxicity study in the male rat.

Male rats were maintained on water or on 10% ethanol drinking fluid. They were pairfed for 30 d prior to exposure to simulated high altitude (approximately 6000 m) and for 78 d, during which they were exposed to simulated high altitude on alternate days. Corresponding controls were maintained at ambient pressure. The high-altitude animals showed loss in liver and epididymis weights compared to respective water controls as contrasted with increased spleen weight in ethanol-drinking rats exposed to high altitude. Hepatic mitochondrial aldehyde dehydrogenase (ALDH) was decreased, compared to controls, by hypobarometric pressure in water-drinking animals. Ethanol intake negated this effect. The kinetics of this inhibition show changes in Vmax without concomitant changes in the apparent Km. Hepatic alcohol dehydrogenase did not change by either treatment. Testicular and epididymal ALDH showed, statistically, no significant changes in specific activity as a function of exposure to high altitude. However, combined ethanol drinking and altitude exposure increased epididymal ALDH compared to water-drinking rats subjected to the same experimental conditions. The changes in liver and testicular weight and in the enzyme involved in the biotransformation of ethanol-derived acetaldehyde suggest the contribution of endocrinological and biochemical factors to hypoxia and to ethanol-evoked adverse responses studied.

Aldehyde Dehydrogenase↗
PubMed1981

Effect of pharmacologic interventions on aldehyde dehydrogenase in the rat testicles.

The in vitro and in vivo effects of selected pharmacologic agents on cytosolic aldehyde dehydrogenase in the adult rat testicles were studied. Naltrexone, a narcotic antagonist, significantly inhibited epididymal but not testicular aldehyde dehydrogenase in vitro. Greater in vitro inhibition of aldehyde dehydrogenase in the epididymal preparation was determined in the presence of diphenhydramine, a histamine H1-receptor antagonist and by amantadine hydrochloride, an antiviral/antiparkinsonian agent. The latter drug also inhibited testicular aldehyde dehydrogenase from corresponding controls. The in vitro inhibition was noncompetitive as evaluated by reciprocal plots of the velocity of the reaction as a function of substrate concentrations. Short-term oral administration of a biologically active metabolite of flutamide, a nonsteroidal antiandrogen, significantly induced testicular aldehyde dehydrogenase without concomitant changes in epididymal aldehyde dehydrogenase from respective controls. Conversely, administration of ethinylestradiol, an estrogenic steroid, inhibited testicular but not epididymal aldehyde hydrogenase in the rat.

Aldehyde Dehydrogenase↗
PubMed1981

Effect of alkali metal salts on Sarcoma I in A/J mice.

The chloride salts of lithium (Li+) and cesium (Cs+) were evaluated for their ability to influence the growth of Sarcoma I implants in A/J mice. The administration of daily doses of either 1 or 3 mEq/kg CsCl to these mice reduced the incidence and size of tumor implants. This effect was not apparent in animals receiving a smaller dose (0.5 mEq/kg) of the same drug. At the time of sacrifice the serum level of Cs+ in this latter group was approximately half that recorded in animals receiving the higher doses of CsCl. No effect on tumor incidence or rate of growth was observed in animals receiving different doses of LiCl. Because of the similarities that existed between cesium and potassium, it was postulated that the effect of cesium was due to alterations in the intracellular composition of the tumor cells. Also, the possible role of cytotoxic agents in potentiating the inhibitory effect of cesium on tumors was discussed.

Animals↗
PubMed1981

Distribution and kinetic properties of alcohol and aldehyde-dehydrogenase in the rat testis.

The distribution of both alcohol (ADH) and aldehyde-dehydrogenase (ALDH) was studied in the rat testis. Testicular ADH was mainly localized into the interstitial tissue. Testicular ALDH activity was distributed between the interstitial tissue and the seminiferous tubules with greater activity measured in the former component. The apparent Km for ADH in the whole testis was greater than that measured in the interstitial tissue. A low Km value was determined for ALDH in the seminiferous tubules, compared to a higher mean Km value for this enzyme in the interstitial tissue of the testis. The study shows that interstitial tissue possesses both ADH and ALDH, which are essential for the respective metabolism of ethanol and acetaldehyde, and that the seminiferous tubules possesses greater affinity for the metabolism of acetaldehyde than that of the interstitial tissue.

Acetaldehyde↗
PubMed1981

Subcellular localization and biochemical properties of rat testicular alcohol- and aldehyde-dehydrogenase.

The biochemical properties and the subcellular distribution of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the rat testis is reported. Both enzymes are NAD-dependent. Testicular ADH activity was found in the nuclear and in the cytosolic fractions. Measurable ALDH was determined in the nuclear, mitochondrial, cytosolic and in the microsomal preparations. The major activity of ADH and ALDH were assayed in cytosol fraction. Cytosolic ALDH possesses lower Km than that determined in the mitochondrial and in the microsomal fractions. The results suggest the presence of multiple active form of testicular ALDH, possibly isoenzymes.

Aging↗
PubMed1981

Subcellular fractionation of alcohol and aldehyde dehydrogenase in the rat testicles.

The subcellular distribution of the enzymes primarily involved in the metabolism of ethanol and acetaldehyde were made in the rat testis and in the epididymis. The enzymes measured were alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). They were NAD-dependent, temperature sensitive and displaying maximal activity in the presence of pyrophosphate buffer at pH 9.8. Both enzymes were readily measurable in the 10% (w/v) testicular and epididymal homogenates. The ADH activity was mainly localized in the nuclear and in the cytosolic fractions of the testis compared to the absence of measurable ADH activity in the epididymis. Testicular ALDH was measurable in all subcellular preparations, i.e. in the nuclear, in the mitochondrial, in the cytosolic and in the microsomal fractions. Maximal testicular ALDH activity was determined in both the nuclear and the cytosolic components compared to a lower microsomal ALDH activity. Determination of Km shows that cytosolic ALDH possesses the lowest apparent Km as contrasted with a high value for the mitochondrial ALDH. Testicular cytosolic ADH but not ALDH was noncompetitively inhibited by 3-methoxytyramine, histamine and d-amphetamine in vitro.

Alcohol Dehydrogenase↗
PubMed1981

Steroidal actions and voluntary drinking of ethanol by male and female rats.

The effect of certain steroidal compounds with estrogenic and antiestrogenic properties on voluntary intake of ET by rats with preference to ET of both sexes was studied. The effect of a nonsteroidal antiandrogenic compound and its biologically active metabolite (SCH-16423) on these parameters was also evaluated. The observed behavioral drinking profile of ET was studied in conjunction with determination of L-ADH and L-ALDH as a function of drug treatment in both sexes. Acute administration of estrogenic compounds, estradiol and ethinyl estradiol, decreased voluntary drinking of ET by male and female rats, respectively. Short-term administration of the antiestrogenic compound TMX resulted in aversion to ET consumption in the male but not in the female rat. Acute administration of the SCH-16423 but not its parent nonsteroidal antiandrogen compound FL decreased ET drinking from predrug treatment. The biochemical results show an inhibitory action by the steroidal compound on hepatic L-M-ALDH with a lack of biochemical effect of FL and SCH-16423 on these enzymes. The results are discussed in conjunction with those available in literature to propose a hepatic-gonadal link in the preference to ET drinking and indicate that the underlying mechanism is probably related to the inhibitory action of estrogenic compounds used on L-M-ALDH.

Alcohol Dehydrogenase↗
PubMed1981

Ocular aldehyde dehydrogenase in rodents.

The presence of NAD-dependent ocular aldehyde dehydrogenase in rodents is reported. The enzyme is species and strain-dependent. Ocular ALDH possesses a significantly greater specific activity than that of the hepatic tissue of the species studied. d-Amphetamine non-competitively inhibited rat eye ALDH in vitro. Short-term administration of cyclobenzaprine, a tricyclic compound with muscle relaxant property, induced ocular aldehyde dehydrogenase. This is compared with lack of effect of certain CNS-stimulants, ethanol intake and of a monoamine oxidase inhibitor on endogenous ALDH in vivo.

Aldehyde Dehydrogenase↗
PubMed1981

Epididymal aldehyde dehydrogenase: a pharmacologic profile.

The in vivo effect of various agents, with different pharmacologic properties, on cytosolic EP-ALDH was studied in the rat. Injection of a large dose of PYZ inhibited EP-ALDH 16 h after the injection. Short-term administration of a moderate daily dosage of PYZ also inhibited endogenous EP-ALDH from saline controls. Semichronic administration of a small daily dosage of DIS resulted in inhibition of EP-ALDH. Short-term administration of drugs with various pharmacologic profile produced little change in the specific activity of EP-ALDH. This is compared with an induction and an inhibition of T-ALDH as a function of treatment with an antiandrogen and an estrogenic drug, respectively. The results show lack of response of EP-ALDH towards pharmacologic intervention which may imply certain specificity for EP-ALDH.

Administration, Oral↗
PubMed1981

Species-dependent ocular aldehyde dehydrogenase.

The presence of ocular NAD-linked aldehyde dehydrogenase is demonstrated in four species. The specific activity and Vmax of the enzyme is greater in ocular tissue drained from aqueous fluid and without the lens compared to the intact eye. The apparent Km remained essentially unchanged for both of these ocular preparations in the species studied.

Aldehyde Dehydrogenase↗
PubMed1980

Testicular and epididymal aldehyde dehydrogenase in rodents: modulation by ethanol and disulfiram.

The distribution of (newly found) NAD-dependent aldehyde dehydrogenase (ALDH) was determined in the rat testis and epididymis as a function of age. There were changes in specific activity of testicular ALDH as a function of age. Epididymal ALDH, which is found evenly distributed between the caput and cauda epididymis, increased initially from the 20th day after birth to th 50th day and remained little altered thereafter in both the caudet and the caput portion of the epididymis. Testicular and epididymal ALDH were found species-dependent with the hamster testis and the rat epididymis showing greater specific activities from the rest of the species studied, respectively. Determinations of testicular ALDH in various mouse strains indicate that it is strain-dependent. Intake of 25% (v/v) ethanol solution as the sole drinking fluid for 10 consecutive days inhibited testicular ALDH in the three mouse strains studied. Administration of disulfiram, 15 mg/kg/day for 60 consecutive days, exerted inhibitory action on testicular and epididymal ALDH in the rat. Intraperitoneal injection of pyrazol, 100 mg/kg once daily for 7 days, resulted in inhibition of epididymal but not of testicular ALDH. It is suggested that testicular and epididymal ALDH may play a role in the toxic action of ethanol-derived acetaldehyde on the gonad.

Alcohol Oxidoreductases↗
PubMed1980

Effect of acute and chronic simulated high altitude on male reproduction and testosterone level.

Forty, sexually mature, male rats were divided into two control and two treated groups. One of the treated groups was exposed five times to 6000 m of high altitude (acute exposure), and the other treated group was exposed 70 times (chronic exposure). Acute exposure had no pathological effect on the male reproductive tract or blood testosterone level; however, in animals that received chronic exposure, there was significant reduction in plasma testosterone level, 80% of spermatogenic tissue was highly vacuolated, nuclei of the interstitial tissue revealed pyknosis, and dilation of the blood vessels was noted throughout the testis.

Altitude↗
PubMed1980

Studies on ethanol and oral contraceptives: feasibility of a hepatic-gonadal link.

Adult male and female rats were subjected to gonadectomy by means of surgical removal of the gonads. In the male, castration resulted in a significant decrease in both body and liver weights compared to intact controls, which persisted for at least 3 weeks. Conversely, ovariectomy was associated with a significant enhancement in both growth rate and liver weight from intact controls. Castration of male rats resulted in induction of hepatic L-ADH (cytosolic alcohol dehydrogenase) and L-ALDH (cytosolic aldehyde dehydrogenase) as contrasted with inhibition of mitochondrial ALDH which was evident in the enzyme with the apparent high Km. Kinetic studies indicate that there was an increase in apparent Km of L-ADH, and hence reduced affinity to hepatic metabolism of ethanol as a consequence of castration in the male rat. This is compared with few changes occurring in the apparent Km value of L-ALDH. Ovariectomy did not alter endogenous L-ADH or L-ALDH. Short-term administration of a synthetic estrogenic steroid ethinyl estradiol, inhibited liver mitochondrial ALDH in the intact female rat but not in the ovariectomized female. Short-term administration of the same dose of an androgen, testosterone, did not alter specific activities of the liver enzymes measured in the intact or in the castrated male rat. Administration of both components of OCs (oral contraceptives) combined or the estrogen alone in behavioral experiments profoundly reduced ethanol drinking by voluntary intake of diluted ethanol solution by the intact female rat. These results suggest a hepatic-gonadal link may exist and that a toxic interaction between the OCs and alcohol drinking is definitely possible.

Alcohol Drinking↗
PubMed1980

Cholinergic, anticholinergic agents and hepatic ethanol metabolizing enzymes.

The in vitro effects of some cholinergics and an anticholinergic agent on hepatic liver alcohol and aldehyde-dehydrogenase were investigated. Physostigmine was the only cholinomimetic agent which significantly inhibited hepatic mitochondrial aldehyde-dehydrogenase without concomitant changes in specific activity of alcohol dehydrogenase. This inhibitory action of physostigmine is found to be competitive and is confined to the enzyme with the low Km value which is also known to be inhibited by disulfiram. Kinetic studies were made to determine changes in the apparent Km value of aldehyde dehydrogenase by physostigmine. Additional experiments were performed to evaluate the Ki50 of physostigmine. The results are discussed in relevance to possible physostigmine-ethanol interaction and the complication of physostigmine in post-operative recovery procedures in individuals with alcohol intoxication and/or in alcoholic patients.

Alcohol Oxidoreductases↗