Biomedical subjects

A M al-Bekairi

Publications and source records attributed to A M al-Bekairi.

At least 19 recordsLinked to original sources

PubMed2000

Pathomorphological changes in mouse liver and kidney during prolonged valproate administration.

Mice given sodium valproate 0.71% weight/volume in drinking water for 7, 14 and 21 days were assessed for pathomorphological changes in liver and kidney tissues at certain time points. This treatment caused a marked alteration in liver and kidney cell morphology, which was proportional to the period of treatment. This treatment induced fatty degeneration of hepatocytes, increased the number of Kupffer cells and caused them to swell. These changes were irregular after days 7 and 14 of treatment but with time increased in intensity, producing inflammation of the portal tracts, albuminous degeneration and necrosis of septa. Precirrhotic conditions, cirrhosis, acidophilic degeneration of hepatocytes and glassy eosinophilic homogenous cytoplasm were a constant feature after 21 days' treatment. In some cases the portal area was invaded by small, round inflammatory cells. Hepatocytes in this group were swollen, with large nuclei and increased amounts of condensed chromatin. The kidney sections of the same animals revealed severe morphological changes, indicated by significant epithelial necrosis and sloughing of tubules, as well as cast formation and mild lymphocytic infiltrate after 21 days' treatment. The results suggest that the histopathologic changes induced by sodium valproate are dependent upon the duration of exposure of these organs to the drug. Prolonged use of this drug should be carefully assessed.

Animals↗

PubMed1999

Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism.

Thymoquinone (TQ) is the major active component of the volatile oil of Nigella sativa seeds. The effects of TQ on carbon tetrachloride (CCl4)-induced hepatotoxicity was investigated in male Swiss albino mice. Carbon tetrachloride (20 microliters/Kg, i.p.) injected into mice, induced damage to liver cells and was followed by the increase in serum alanine aminotransferase (ALT) activity after 24 h. Oral administration of TQ in a single dose (100 mg/Kg) resulted in significant (p < 0.001) protection against the hepatotoxic effects of CCl4. TQ was tested as a substrate for mice hepatic DT-diaphorase in the presence of NADH. TQ appears to undergo reduction to dihydrothymoquinone (DHTQ). Reduction rates as a function of protein (liver homogenate) and substrate (TQ) concentrations are reported. An apparent K(m) of 0.1 mM and an apparent Vmax of 74 mumol/min/g liver were measured. TQ and DHTQ inhibited the in vitro non-enzymatic lipid peroxidation in liver homogenate (induced by Fe(3+)-ascorbate) in a dose dependent manner. In this in vitro model DHTQ was more potent in comparison with TQ and butylated hydroxytoluene (BHT). The IC50 for DHTQ, TQ and BHT were found to be 0.34, 0.87 and 0.58 microM respectively. The data suggest that the in vivo protective action of TQ against CCl4-induced hepatotoxicity may be mediated through the combined antioxidant properties of TQ and its metabolite DHTQ.

Alanine Transaminase↗

PubMed1998

Vitamin E protects the brain against oxidative injury stimulated by excessive aluminum intake.

The effect of feeding groups of mice with a diet containing 2000, 4000 and 6000 micrograms aluminum (Al3-/g) for two weeks (subacute) or 2000 and 4000 micrograms Al3+/g for eight weeks (subchronic) as well as the coadministration of vitamin E (alpha-tocopherol) 500 micrograms/g with Al3+, on the status of glutathione (GSH) and lipid peroxides as thiobarbituric acid reactive substances (TBARS) in whole brain tissues were evaluated. Changes in TBARS were further evaluated in vitro following the incubation of brain homogenates of the Al(3+)-fed mice in the presence of 50 microM FeSO4. The results of subacute experiments revealed that the brain levels of GSH were significantly decreased only in the group of mice that received 6000 micrograms Al3+/g diet (P < 0.05) and this effect was partially ameliorated when vitamin E was coadministered with Al3+. TBARS were significantly increased in vitro only in the presence of free iron ions and depended on the concentration of Al3+ in the diet. The effect was opposed by the vitamin E intake. Following subchronic Al3+ intake, the GSH content of the brain was significantly decreased only in the group of mice that received 4000 micrograms Al3+/g diet (P < 0.01), while TBARS were significantly increased in the brain tissues in vivo as well as in the presence of free iron ions in vitro. However, coadministration of vitamin E with Al3+ for eight weeks preserved GSH levels and decreased TBARS in the brain of mice in vivo and in the presence of free iron ions in vitro. It is concluded that the long term administration of vitamin E may prevent Al3(+)-stimulated oxidative injury in the brain.

Aging↗

PubMed1998

Thymoquinone protects against doxorubicin-induced cardiotoxicity without compromising its antitumor activity.

Doxorubicin (DOX) has a wide spectrum of antitumor activity with dose-related cardiotoxicity as a major side effect. This cardiotoxicity has been suggested to result from the generation of oxygen-free radicals. The objective of the present study was to investigate the influence of the antioxidant, thymoquinone (TQ) on cardiotoxicity and antitumor activity of DOX in mice. TQ (8 mg/kg/day, p.o.) administered with drinking water starting 5 days before a single i.p. injection of DOX (20 mg/kg) and continuing during the experimental period ameliorated the DOX-induced cardiotoxicity in mice. This finding was evidenced by significant reductions in serum lactate dehydrogenase and creatine kinase elevated levels and further supplemented by histopathological examination of cardiac tissue. TQ did not alter the plasma and heart DOX levels as monitored by fluorometric analysis. In in vivo study on mouse Ehrlich ascites carcinoma tumor, it could then be shown that TQ does not interfere with the antitumor activity of DOX. The current data support TQ as a potentially selective cytoprotective agent, which may ameliorate cardiotoxicity without decreasing DOX antitumor activity.

Animals↗

PubMed1997

Antinociceptive activity of sodium valproate in mice after chronic treatment.

1. Mice were given sodium valproate (0.71%) in the drinking fluid for 21 days. The antinociceptive activity, locomotor activity and body temperature changes were recorded at 7, 14 and 21 days. The possible carryover antinociceptive effects were also determined after valproate withdrawal for up to 3 days after 7-, 14- and 21-day treatment. 2. The antinociceptive activity was present only on days 7, 14 and 21 and, on withdrawal of the drug, the antinociceptive activity disappeared. 3. Thus, with this regimen of valproate administration, there was no persistent antinociceptive activity (carryover effect). There were essentially no effects of valproate on the locomotor activity and body temperature of mice. The antinociceptive effects were due to the presence of the drug and disappeared on valproate's withdrawal.

Analgesics↗

PubMed1997

Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity.

The effects of thymoquinone (TQ) on cisplatin-induced nephrotoxicity in mice and rats were studied. Oral administration of TQ (50 mg/L in drinking water) for 5 days before and 5 days after single injections of cisplatin (5 mg/kg, i.v., in rats and 7 or 14 mg/kg, i.p., in mice) greatly ameliorated cisplatin-induced nephrotoxicity in both species. In rats, i.v. cisplatin caused 4- and 5-fold elevations in serum urea and creatinine, a 235% increase in urine volume, a 41% increase in kidney weight, 8.5-fold decrease in creatinine clearance, and extensive histological damage 5 days after treatment. In mice, similar alterations in kidney function were observed. TQ-induced amelioration of cisplatin nephrotoxicity was evident by significant reductions in serum urea and creatinine and significant improvement in polyuria, kidney weight, and creatinine clearance. The protective effects of TQ against cisplatin-induced nephrotoxicity in the rat were further confirmed by histopathological examination. To evaluate the possible modification of the antitumor activity of cisplatin by TQ, we studied their interaction in Ehrlich ascites carcinoma (EAC) bearing mice. The results revealed that TQ potentiated the antitumor activity of cisplatin. The current study suggests that TQ may improve the therapeutic index of cisplatin.

Animals↗

PubMed1995

Spectrophotometric assay for superoxide dismutase based on the nitroblue tetrazolium reduction by glucose-glucose oxidase.

A new spectrophotometric assay of superoxide dismutase (SOD) is described. The assay is based on the SOD-mediated inhibition in the rate of nitroblue tetrazolium reduction to the blue formazan at alkaline pH. The optimized assay of SOD is performed in 50 mM glycine-NaOH buffer, pH 9.5, at 25 degrees C. The SOD concentration is determined from the V/v ratio of rates measured in the absence (V) or the presence (v) of SOD. One unit of SOD has been defined as the concentration that decrease the rate to 50% (V/v = 2). The assay is simple, sensitive, uses commercially available reagents, rapid and easy to perform and could be used routinely for monitoring superoxide dismutase levels in purified protein fractions.

Aspergillus niger↗

PubMed1994

Effect of (+/-)-verapamil and hydralazine on stress- and chemically-induced gastric ulcers in rats.

The influence of (+/-)-verapamil and hydralazine on stress- and various chemically-induced gastric ulcers in rats together with their influence on various biochemical parameters which affect the development of the induced ulcers was examined. Pretreatment of rats with (+/-)-verapamil (4-16 mg kg-1 orally) significantly decreased cold-stress-induced gastric ulcers and enhanced ethanol-induced ulcers. It did not affect indomethacin- (30 mg kg-1 orally) or reserpine- (5 mg kg-1 i.p.) induced ulcers. Pretreatment of the animals with hydralazine (1-10 mg kg-1 orally) significantly enhanced ethanol-, reserpine- and cold-stress-induced ulcers. It did not affect indomethacin-induced ulcers. Pretreatment of the animals with verapamil increased gastric mucus secretion, inhibited gastric acid secretion, decreased glutathione content and enhanced gastric lipid peroxidation whereas pretreatment of the animals with hydralazine significantly decreased gastric mucus secretion. Hydralazine did not affect gastric acid secretion, glutathione or gastric lipid peroxidation. The results of this study suggest that verapamil-induced protection against stress-induced ulcer may be due to its ability to suppress gastric acid secretion and to increase gastric mucus secretion. Its enhancement of ethanol-induced ulcers may be due to its ability to increase lipid peroxidation. The hydralazine-induced enhancement of the experimentally-induced ulcers may be due to its ability to suppress gastric mucus secretion.

Animals↗

PubMed1994

Evidence for superoxide radical production by a simple flavoprotein: glucose oxidase.

Nitroblue tetrazolium was reduced to blue formazan during the oxidation of glucose by glucose oxidase. The rate of blue color formation was dependent on the concentrations of glucose, nitroblue tetrazolium and glucose oxidase. The rate of the reaction was negligible below pH 8.4, but sharply increased with increasing pH. The reduction of nitroblue tetrazolium was inhibited by superoxide dismutase, consistent with the participation of superoxide anion radical in the reaction.

Aspergillus niger↗

PubMed1993

Changes in free amino acids in peripheral blood (PB) lymphocytes and polymorphonuclear (PMN) leukocytes after treatment with diazepam.

The effect of single and chronic (15 days) i.p. injections (1.0 and 8.0 mg/kg) of diazepam (DZ) on free amino acid profile in peripheral blood (PB) lymphocytes and polymorphonuclear (PMN) leukocytes of male Wistar Albino rats were investigated. Depletion of some free amino acids was observed in the lymphocytes (mixed T- and B-lymphocytes) and PMN leukocytes (91-95%) neutrophils especially after chronic DZ-treatment. A dose-dependent depletion in the lymphocyte amino acids, Tau, Gly, Ala, Met and Ile, was found after both acute and chronic DZ-treatment. A similar depletion of Tau, Asp, Glu and Met appeared in the PMN leukocytes after single doses as well as chronic DZ-treatment. These results suggest that administration of 1.0-8.0 mg/kg of DZ in single dose or after chronic administration may interfere with the transport of certain important amino acids and/or protein turnover in PB lymphocytes and PMN leukocytes. On the other hand, the basic amino acids Lys, His and Arg were significantly increased in PMN leukocytes after chronic administration of 1.0 mg/kg DZ. It was suggested that the increased levels of the basic amino acids in the neutrophils may interact with the intracellular changes in pH that normally accompany the respiratory burst.

Amino Acids↗

PubMed1993

The ocular effects of spitting cobras: I. The ringhals cobra (Hemachatus haemachatus) venom-induced corneal opacification syndrome.

Venom from the ringhals cobra (H. haemachatus) caused extensive chemosis, prolonged corneal edema and marked miosis when applied locally to the eyes of two strains of rabbits: Buskat (albino) and Chinchilla (pigmented). In the pigmented rabbits, the corneal edema progressed to complete corneal opacification with corneal and conjunctival neovascularization that remained unchanged until the end of the experiment (70 d). In the albino rabbits the corneal cloudiness and conjunctivitis cleared within three weeks of venom instillation. Treatment with heparin and tetracycline markedly improved the corneal opacification syndrome, while treatment with specific antivenom resulted only in partial improvement. It is postulated that the venom owes its ocular effects to its cardiotoxin, the only venom fraction capable of inducing the corneal opacification syndrome. The protective effect of heparin is probably through its electrostatic binding to the cardiotoxin in the venom. Tetracycline could form ionic bonding at several sites in the strongly basic cardiotoxin. The corneal opacification syndrome was associated with the ability of the snakes to spit since venoms from the other non-spitting cobras were devoid of this activity.

Animals↗

PubMed1993

The ocular effects of spitting cobras: II. Evidence that cardiotoxins are responsible for the corneal opacification syndrome.

Fractionation of H. haemachatus, N. nigricollis, N. nivea and N. melanoleuca venoms using Amberlite CG-50 and (NH4)HCO3 elution gradient chromatography yielded 11-13 fractions for each venom. One fraction, F X, from H. haemachatus, two fractions, F X and F XI, from N. nigricollis and one fraction, F VIII, from N. melanoleuca venoms possessed the whole of ocular activity of the venoms. The fractions were the only venom fractions that caused cardiac depressant activity; their effect was reversed by raising Ca++ concentration in the physiological solution; they did not influence the twitches of the phrenic nerve hemidiaphragm and guinea-pig ileum preparations. Further purification of the fractions on Sephadex G-50 followed by fractionation on Amberlite CG-50 yielded fractions free from phospholipase A2 activity but possessing the same ocular effects. Similarly, the cardiotoxin from commercial N. nigricollis venom caused the same ocular effects as the crude venom and its purified cardiotoxic fractions. All cardiotoxic fractions as well as N. nigricollis cardiotoxin, caused extensive chemosis, blepharitis and corneal opacification with corneal and subconjunctival neovascularization. On a weight basis, the cardiotoxins were weaker in their oculotoxic activity than the corresponding parent crude venoms possibly because of the potentiating effect of phospholipase A2 in the crude venoms. It is postulated that in spitting cobras the cardiotoxins are responsible for the corneal opacification syndrome. In other cobra venoms the stable binding of cardiotoxins with acidic proteins limits their possible ocular effects. Only in the venoms of the spitting species are the cardiotoxins present in an appropriately free form to cause the ocular opacification syndrome.

Animals↗

PubMed1992

Prevention of doxorubicin-induced myocardial and haematological toxicities in rats by the iron chelator desferrioxamine.

Biochemical and histopathological evaluations of the protective effects of the iron-chelator desferrioxamine against the cardiac and haematological toxicities of doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg/kg, i.v.) caused myocardial damage that manifested biochemically as an elevation of serum cardiac enzyme [glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase (LDH) and creatine phosphokinase (CPK)] and cardiac isoenzyme levels and histopathologically as a swelling and separation of cardiac muscle fibers. Doxorubicin caused severe leucopenia and decreases in red blood cell counts and haemoglobin concentrations at 72 h after its administration. Desferrioxamine treatment (250 mg/kg, i.p.) carried out 30 min before doxorubicin administration protected the heart and blood elements from the toxic effects of doxorubicin as indicated by the recovery of levels of cardiac enzymes and isoenzymes and of red blood cell counts to normal values and by the absence of significant myocardial lesions. The findings of this study suggest that desferrioxamine can potentially be used clinically to prevent doxorubicin-induced cardiac and haematological toxicities.

Animals↗

PubMed1992

A study of uric acid pretreatment for the protection of rat gastric mucosa against toxic damage.

Uric acid was evaluated for its potential to protect the gastric mucosa against the injuries caused by 80% ethanol, 0.6 m-HCl and 0.2 M-NaOH in rats. Uric acid at doses of 50, 100 or 300 mg/kg body weight provided dose-dependent protection against the ulcerogenic effects of all three agents. Other effects caused by ethanol only were studied. Serum uric acid concentrations were statistically significantly increased by both uric acid and ethanol treatments. Treatments of rats by gavage with 1 ml 80% ethanol was found to cause depletion of stomach-wall mucus, to lower the concentrations of protein, nucleic acids and non-protein sulphydryl groups in the stomach wall, and to cause histopathological lesions, including necrosis, erosions, congestion and haemorrhage, of the stomach wall. Treatment with uric acid, at doses of 50, 100 or 300 mg/kg body weight, by gavage, provided some measure of protection against all of these effects, and the protection was generally dose dependent. The protective effects of uric acid against damage to the gastric-wall mucosa may be mediated through its effects on mucus production and non-protein sulphydryl concentrations, and/or its free-radical scavenging properties.

Animals↗

PubMed1992

Effect of Caralluma tuberculata on the cytological and biochemical changes induced by cyclophosphamide in mice.

Treatment with Caralluma tuberculata extract induced complex biochemical and cytological changes in mice. Its cytotoxicity in the bone marrow cells of mice was comparable with that of the standard drug cyclophosphamide (CP); however, unlike CP, C. tuberculata was not clastogenic (as shown by the micronucleus assay). A dose-dependent decrease in the RNA content of liver and testes was produced by C. tuberculata treatment whereas there was no effect on the content of nucleic acid and protein in the brain. In the extract-treated animals there was a significant and dose-dependent increase in the DNA content of the liver, with a negligible effect on the protein content. Combined treatment with C. tuberculata and CP showed that C. tuberculata diminished the effect of CP on DNA levels; however, RNA levels were further suppressed, resulting in increased cytotoxicity. Pretreatment with C. tuberculata extract significantly reduced the clastogenicity of CP. These results indicated the involvement of different phytoconstituents acting by different routes.

Animals↗

PubMed1991

Uric acid as an inhibitor of cyclophosphamide-induced micronuclei in mice.

Swiss albino male mice, 6-8 weeks old, were treated orally with different doses of uric acid dissolved in water for 7 days. Some of the mice in each group were injected i.p. with cyclophosphamide (25 mg/kg) and killed after 30 h. The blood of all animals was analyzed for uric acid levels. The femoral cells of the mice in different groups were collected and studied. Uric acid was found to be devoid of mitodepressant or clastogenic activity at 10-100 mg/kg/day. Pretreatment with uric acid was found to provide significant protection against cyclophosphamide-induced bone marrow depression and micronucleated polychromatic erythrocytes.

Animals↗

PubMed1991

Uric acid as an inhibitor of biochemical changes induced by cyclophosphamide in mice.

The biochemical changes induced by uric acid, cyclophosphamide and uric acid plus cyclophosphamide were evaluated in Swiss albino male mice. Uric acid dissolved in water was administered orally in different doses for 7 days. Some mice from each group were injected intraperitoneally with cyclophosphamide (25 mg/kg) and sacrificed after 30 h. The blood of all animals was analyzed for uric acid levels. Uric acid was found not to affect the biosynthesis of nucleic acids and proteins in liver, testes and brain at 10-100 mg/kg/d. Pretreatment with uric acid provided significant protection against cyclophosphamide-induced impairment of DNA, RNA and protein biosynthesis.

Animals↗

PubMed1991

Mitodepressive, clastogenic and biochemical effects of (+)-usnic acid in mice.

Mice were treated orally with aqueous suspensions of (+)-usnic acid in a single dose of either 100 or 200 mg/kg. The effects on femur cells and proteins and on nucleic acids of liver cells were studied 24-72 h after treatment. (+)-Usnic acid was found to affect the proliferation of polychromatic erythrocytes possibly by interference with RNA biosynthesis. The slight increase in the micronucleated polychromatic erythrocytes without affecting DNA synthesis suggests an effect of usnic acid on spindle apparatus.

Administration, Oral↗