scholarly journals Sterodin®, a novel immunostimulating drug: Some toxicological and pharmacological evaluations in vivo, and drug-lipid interaction studies in vitro

2009 ◽  
Vol 59 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Sarbani Ray ◽  
Partha Roy ◽  
Supratim Ray
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Blood Cells ◽  
White Blood Cells ◽  
Pharmacological Properties ◽  
Lipid Source ◽  
Interaction Studies ◽  
Lipid Interaction

Sterodin®, a novel immunostimulating drug: Some toxicological and pharmacological evaluations in vivo, and drug-lipid interaction studies in vitro Sterodin® is a novel non-specific immunostimulating drug produced by a combination of bile lipids and bacterial metabolites. In the present study, we investigated some of its (i) toxicological and (ii) pharmacological properties in vivo, and (iii) drug-lipid interaction (lipid peroxidation) in vitro. We also evaluated the possible (iv) Sterodin®-induced lipid peroxidation as well as the effect of ascorbic acid on this peroxidation. We found LD50 of Sterodin® to be 31.50 mL kg-1 body mass. In male albino mice, Sterodin® increased the total white blood cells and neutrophils count by 59 and 26%, respectively, on the 6th day, compared to day 0 after injection and stimulated phagocytic activity in vivo. We used goat liver as lipid source in drug-lipid interaction studies in vitro. Our experiments show that Sterodin® induces lipid peroxidation, which was prevented by ascorbic acid.

scholarly journals Cytotoxicity and Genotoxicity Evaluation of Organochalcogens in Human Leucocytes: A Comparative Study between Ebselen, Diphenyl Diselenide, and Diphenyl Ditelluride

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Diones Caeran Bueno ◽  
Daiane Francine Meinerz ◽  
Josiane Allebrandt ◽  
Emily Pansera Waczuk ◽  
Danúbia Bonfanti dos Santos ◽  
...  
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Pharmacological Properties ◽  
Potential Toxicity ◽  
Early Step ◽  
Preliminary Model ◽  
Diphenyl Ditelluride ◽  
Acute Cytotoxicity

Organochalcogens, particularly ebselen, have been used in experimental and clinical trials with borderline efficacy. (PhSe)2and (PhTe)2are the simplest of the diaryl dichalcogenides and share with ebselen pharmacological properties. In view of the concerns with the use of mammals in studies and the great number of new organochalcogens with potential pharmacological properties that have been synthesized, it becomes important to develop screening protocols to select compounds that are worth to be testedin vivo. This study investigated the possible use of isolated human white cells as a preliminary model to test organochalcogen toxicity. Human leucocytes were exposed to 5–50 μM of ebselen, (PhSe)2, or (PhTe)2. All compounds were cytotoxic (Trypan’s Blue exclusion) at the highest concentration tested, and Ebselen was the most toxic. Ebselen and (PhSe)2were genotoxic (Comet Assay) only at 50 μM, and (PhTe)2at 5–50 μM. Here, the acute cytotoxicity did not correspond within vivotoxicity of the compounds. But the genotoxicity was in the same order of thein vivotoxicity to mice. These results indicate thatin vitrogenotoxicity in white blood cells should be considered as an early step in the investigation of potential toxicity of organochalcogens.

Phytochemical analysis and nephroprotective effect of cactus (Opuntia ficus-indica) cladodes on sodium dichromate-induced kidney injury in rats

2019 ◽  
Vol 44 (3) ◽  
pp. 239-247
Author(s):  
Mbarka Hfaiedh ◽  
Dalel Brahmi ◽  
Mohamed Nizar Zourgui ◽  
Lazhar Zourgui
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Wistar Rat ◽  
Phytochemical Analysis ◽  
Sodium Dichromate ◽  
Opuntia Ficus Indica

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium, is widely recognized as potentially nephrotoxic in humans and animals. The present study aimed to assess the efficacy of cactus (Opuntia ficus-indica) against sodium dichromate-induced nephrotoxicity, oxidative stress, and genotoxicity. Cactus cladodes extract (CCE) was phytochemically studied and tested in vitro for its potential antioxidant activities. Additionally, the preventive effect of CCE against sodium dichromate-induced renal dysfunction in a Wistar rat model (24 rats) was evaluated. For this purpose, CCE at a dose of 100 mg/kg was orally administered, followed by 10 mg/kg sodium dichromate (intraperitoneal injection). After 40 days of treatment, the rats were sacrificed, and the kidneys were excised for histological, lipid peroxidation, and antioxidant enzyme analyses. The phenol, flavonoid, tannin, ascorbic acid, and carotenoid contents of CCE were considered to be important. Our analyses showed that 1 mL of CCE was equivalent to 982.5 ± 1.79 μg of gallic acid, 294.37 ± 0.84 μg of rutin, 234.78 ± 0.24 μg of catechin, 204.34 ± 1.53 μg of ascorbic acid, and 3.14 ± 0.51 μg of β-carotene. In vivo, pretreatment with CCE was found to provide significant protection against sodium dichromate-induced nephrotoxicity by inhibiting lipid peroxidation, preserving normal antioxidant activities, and protecting renal tissues from lesions and DNA damage. The nephroprotective potential of CCE against sodium dichromate toxicity might be due to its antioxidant properties.

Genotoxic effects in human white blood cells following styrene (in vivo) and styrene oxide (in vitro) exposure

1998 ◽  
Vol 95 ◽  
pp. 41
Author(s):  
B. Marczynski ◽  
M. Peel ◽  
P. Rozynek ◽  
J. Elliehausen ◽  
M. Korn ◽  
...  
Keyword(s):  
Blood Cells ◽  
Styrene Oxide ◽  
White Blood Cells ◽  
Genotoxic Effects ◽  
In Vitro Exposure ◽  
Human White Blood Cells

scholarly journals Vitamin E and stress

1967 ◽  
Vol 21 (3) ◽  
pp. 671-679 ◽  
Author(s):  
M. A. Cawthorne ◽  
A. T. Diplock ◽  
I. R. Muthy ◽  
J. Bunyan ◽  
Elspeth A. Murrell ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Vitamin E ◽  
Lipid Peroxide ◽  
Toxic Effects ◽  
Peroxide Content ◽  
In Vitro Techniques ◽  
Sulphydryl Compounds

1. Vitamin E-deficient rats were found to be more susceptible than vitamin E-supplemented controls to the toxic effects of hyperbaric oxygen (60 lb/in.2 for 20 min). This agrees with the findings of other workers.2. Hyperbaric O2 treatment did not increase the metabolic destruction of a small amount (46.65 μg) of [14C-5-Me]D-α-tocopherol given to adult vitamin E-deficient rats 24 h previously. The O2 treatment also did not affect the soluble sulphydryl compounds and ascorbic acid of rat liver, nor the percentag haemolysis in vivo of rat blood.3. Hyperbaric O2 treatment did not increase the true lipid peroxide content of rat brain, compared to control rats treated with hyperbaric air, which has no toxic effects. Increases in ‘lipid peroxidation’ reported by previous workers are considered to have been due to the use of inadequate controls (untreated rats) and of in vitro techniques that are open to criticism.4. The toxic effects of hyperbaric O2 in the vitamin E-deficient rat cannot be attributed to peroxidation in vivo.5. Vitamin E was not found to protect rats against the effects of reduced O2 tension (anoxic anoxia). This finding contrasts with some reports by earlier workers. Reduced O2 tension had no effect on the metabolism of radioactive tocopherol, on blood haemolysis in vivo, or on the soluble sulphydryl compounds and ascorbic acid of liver.

scholarly journals Familial deficiency of glutathione reductase in human blood cells

Blood ◽  
1976 ◽  
Vol 48 (1) ◽  
pp. 53-62 ◽  
Author(s):  
H Loos ◽  
D Roos ◽  
R Weening ◽  
J Houwerzijl
Keyword(s):  
Glutathione Reductase ◽  
Blood Cells ◽  
Normal Values ◽  
Reductase Activity ◽  
White Blood Cells ◽  
Human Blood Cells ◽  
Glutathione Reductase Activity ◽  
Fava Beans

A virtually complete absence of glutathione reductase activity was found in the erythrocytes of all three children (one male, two females) from a consanguineous marriage. Intermediate values were found in the erythrocytes of both parents. The enzyme activity could not be restored either by addition of FAD in vitro or by administration of riboflavin in vivo. The amount of reduced glutathione in the erythrocytes was normal in each case. Severely diminished glutathione stability during incubation with acetylphenylhydrazine was observed in the erythrocytes of the siblings, as well as intermediate stability in the parents' red cells. Clinically, this deficiency was manifested by hemolytic crises after eating fava beans in the eldest daughter (patient), and possibly by cataracts in her own and in her brother's eyes. Very low activities of glutathione reductase were also found in the leukocytes of this family: 13%-15% of normal values for the children and 64%-66% for the parents. Moreover, the same deficiency was found in the purified white blood cells of the propositus: 8% of normal values in the polymorphonuclear (PMN) cells, 4% in the lymphocytes, and 15% in the monocytes, together with 11% in the platelets. Finally, we found an abnormal oxygen consumption of the propositus' PMNs after phagocytosis of zymosan particles, suggesting that the glutathione reductase reaction was involved in the bactericidal capacity of these cells.

Very Rapid Clearance after a Joint Bleed Knee Can Not Prevent Adverse Effects on Cartilage and Synovial Tissue: A Canine in Vivo Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2273-2273
Author(s):  
Nathalie W.D. Jansen ◽  
Goris Roosendaal ◽  
Marion Wenting ◽  
Herman A.W. Hazewinkel ◽  
Johannes W.J. Bijlsma ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Knee Joint ◽  
Synovial Tissue ◽  
Blood Cells ◽  
White Blood Cells ◽  
Synthesis Rate ◽  
Rapid Clearance

Abstract Purpose Joint bleeds lead to joint destruction. In vitro exposure of human and canine cartilage to blood results in long lasting severe adverse changes in cartilage. An in vivo joint haemorrhage in the canine knee joint demonstrates similar adverse effects although less outspoken and long-lasting. We investigated the clearance rate of blood from canine knee joints as a possible explanation for this discrepancy. Methods Blood was injected into the knee joint of Beagle dogs, either 48h, 24h or 15m before termination. The amount of red and white blood cells present in the joint cavity was determined. Chondrocyte activity and cartilage matrix integrity as well as cartilage destructive activity of synovial tissue were determined biochemically. Additionally, synovial tissue was analyzed by use of histochemistry. Results Fifteen minutes after the injection of autologous blood, the red blood cell count was 5,7*1012/L, comparable to the amount present in whole blood, and gradually decreased (1,6*1012/L at 24 hours) to 0,2*1012/L within 48 hours (less than 5%). The amount of white blood cells increased in the first 24 hours, and was still increased after 48 hours, although less than after 24 hours. The proteoglycan synthesis rate and -release were adversely affected already within 24 hours (−22% and +24% respectively), and these effects were more severe 48 hours post-injection (−34% and +53% resp.). Synovial tissue culture supernatants demonstrate cartilage destructive properties as expressed by an increased release, a decreased synthesis rate, and decreased content of cartilage proteoglycans; increasing with time after the experimental haemorrhage (+207%/+247%; −58%/−62%; −8%/−28% respectively, for 24/48 hours). Evaluation of the synovial tissue revealed at 15 minutes post-injection countless numbers of intact RBC that were almost completely disappared after 48 hours, withonly limited recruitment of macrophages and iron deposition. Conclusions Blood is cleared very rapidly from the canine knee joint, but in that short time span already has adverse effects on both cartilage and synovial tissue. This rapid clearance can play a role in the discrepancy between long-term in vitro and in vivo effects of blood-induced joint damage since more than 10% v/v blood for 48 hours is needed induced to long-term adverse effects in vitro. Irrespectively, blood has devastating effects on articular cartilage very rapidly, and in this respect it is important to prevent (traumatic) joint haemorrhages and if they occur, to treat them properly.

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