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1.
Int J Surg Case Rep ; 113: 109034, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37980773

ABSTRACT

INTRODUCTION: Retained foreign bodies have become very rare in countries where the safety rules in the operating theater are very rigorous and follow precise guidelines. Maintaining awareness of this issue among surgeons and radiologists is of paramount importance to minimize avoidable morbidity and facilitate the selection of the most suitable therapeutic strategy. This consideration is particularly relevant in the differential diagnosis of hydatid cysts. This study describes a case of intra-abdominal gossypiboma, which mimicked hydatid cyst on preoperative assessment. CASE PRESENTATION: We report the case of a 63-year-old female who was referred to our department for the management of a hepatic hydatid cyst. She has history of open cholecystectomy and oophorocystectomy. During the intervention, we discovered a 10 cm mass located in the interhepatogastric region. Complete resection of the mass was performed, and pathology results were compatible with a piece of gauze surrounded by reactive changes (gossypiboma). DISCUSSION: Gossypiboma is undeniably a source of concern for surgeons. It's a genuine and serious surgical complication which can potentially arise from any type of surgery and may manifest with diverse complaints. However, it is crucial to emphasize that this complication is preventable with the primary preventive measure being meticulous counting of surgical materials during the procedure. CONCLUSION: The potential embarrassment experienced by the surgeon and the significant legal consequences associated with this iatrogenic complication are substantial. Hence, it becomes imperative to adopt all requisite preventive measures to avert such incidents, as there is no excuse that can justify their occurrence.

3.
Diabetes Obes Metab ; 12(2): 148-57, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19788435

ABSTRACT

AIM: Nigella sativa (N. sativa) is a plant widely used in traditional medicine of North African countries. During the last decade, several studies have shown that extracts from the seeds of N. sativa have antidiabetic effects. METHODS: Our group has recently demonstrated that N. sativa seed ethanol extract (NSE) induces an important insulin-like stimulation of glucose uptake in C2C12 skeletal muscle cells and 3T3-L1 adipocytes following an 18 h treatment. The purpose of the present study was to elucidate the pathways mediating this insulin-like effect and the mechanisms through which these pathways are activated. RESULTS: Results from western immunoblot experiments indicate that in C2C12 cells as well as in H4IIE hepatocytes, but not in 3T3-L1 cells, NSE increases activity of Akt, a key mediator of the effects of insulin, and activity of AMP-activated protein kinase (AMPK), a master metabolic regulating enzyme. To test whether the activation of AMPK resulted from a disruption of mitochondrial function, the effects of NSE on oxygen consumption were assessed in isolated liver mitochondria. NSE was found to exhibit potent uncoupling activity. CONCLUSION: Finally, to provide an explanation for the effects of NSE in adipocytes, PPARgamma stimulating activity was tested using a reporter gene assay. Results indicate that NSE behaves as an agonist of PPARgamma. The data supports the ethnobotanical use of N. sativa seed oil as a treatment for diabetes, and suggests potential uses of this product, or compounds derived thereof, against obesity and the metabolic syndrome.


Subject(s)
AMP-Activated Protein Kinases/drug effects , Adipocytes/metabolism , Hypoglycemic Agents/pharmacology , Muscle, Skeletal/metabolism , Nigella sativa/chemistry , Plant Extracts/pharmacology , AMP-Activated Protein Kinases/metabolism , Adipocytes/drug effects , Animals , Blotting, Western , Cells, Cultured , Humans , Muscle, Skeletal/drug effects , PPAR gamma/metabolism , Plant Extracts/chemistry , Seeds/chemistry , Signal Transduction
5.
Rev Med Liege ; 64(12): 633-8, 2009 Dec.
Article in French | MEDLINE | ID: mdl-20143748

ABSTRACT

Desmoids tumors are rare. They often develop from the fascia and muscles of the abdominal wall. They are considered as benign, but endowed with local aggressiveness. Treatment is primarily surgical. Complete resection with large safety margins and sometimes complex reconstruction is necessary to reduce the risk of local reccurrence. WE report three cases of histology proven desmoids tumors of the abdominal wall treated between 2000 and 2007. Etiologic factors, diagnosis, surgical management and adjuvant therapy in case of incomplete resection or reccurrence are discussed.


Subject(s)
Abdominal Wall/surgery , Fibromatosis, Aggressive/pathology , Fibromatosis, Aggressive/surgery , Adult , Female , Humans
6.
Ann Pharm Fr ; 60(2): 123-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11976557

ABSTRACT

Peganum harmala is plant known since the first century A.D. and still, currently used for therapeutic purposes. Harmaline, the active principle of the plant seeds, and its derivatives, cause visual troubles, loss of coordination, agitation and delirium, and, at high doses, it can produce paralysis. The present study was initiated to evaluate the use and manipulation of therapeutic doses of aqueous extract of P. harmala. Wistar rats were orally dosed acutely and the LD(50) obtained was 2.70+/-0.05g/kg. In chronic studies aqueous extract of P. harmala administered orally for six times a week at doses of 1, 1.35 and 2g/kg during 3 month period increased transaminases. Changes in glucose and creatinine were not significant. No significant gross changes were found at necropsy. Histologic study showed liver degeneration and spongiform changes in the central nervous system (CNS) in rats treated with 2g/kg dose but not at the therapeutic dose of 1g/kg.


Subject(s)
Plant Extracts/toxicity , Plants, Medicinal/chemistry , Animals , Hemodynamics/drug effects , Lethal Dose 50 , Liver Function Tests , Rats , Rats, Wistar , Seeds/chemistry
7.
Biochem Pharmacol ; 62(4): 509-16, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11448461

ABSTRACT

We investigated the antiischemic properties of a new compound, S-15176, in an experimental model of rat liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion. Rats were divided into groups, pretreated with different doses of S-15176 (1.25, 2.5, 5 and 10 mg/kg/day by intramuscular injection) or solvent alone, and subjected to the ischemia--reperfusion process. Another group served as the sham-operated controls. Ischemia--reperfusion induced huge alterations of hepatocyte functions, namely, a decrease in ATP content and bile flow, and membrane leakage of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT). These effects were associated with alterations in mitochondrial functions characterized by (1) a decrease in ATP synthesis, (2) a decrease in NAD(P)H levels and mitochondrial membrane potential, and (3) an increase in mitochondrial swelling reflecting the generation of permeability transition. Pretreatment of rats with S-15176 alleviated these deleterious ischemia--reperfusion effects at both the cellular and mitochondrial levels in a dose-dependent manner. The protection of mitochondrial functions was almost complete at a dosage of 10 mg/kg/day. In addition, in vitro, S-15176 totally abolished the swelling of isolated mitochondria induced by a calcium overload with an IC(50) value of 10 microM. These data demonstrate that S-15176 protects mitochondria against the deleterious effects of ischemia-reperfusion and suggest that this protective effect could be related to the inhibition of the mitochondrial permeability transition.


Subject(s)
Hepatocytes/drug effects , Mitochondria, Liver/drug effects , Piperazines/pharmacology , Protective Agents/pharmacology , Adenosine Triphosphate/metabolism , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Bile Ducts/drug effects , Bile Ducts/physiology , Cell Membrane/drug effects , Cell Membrane/metabolism , Dose-Response Relationship, Drug , Hepatocytes/metabolism , Ischemia/pathology , Ischemia/prevention & control , Liver Diseases/pathology , Liver Diseases/prevention & control , Liver Function Tests , Male , Membrane Potentials/drug effects , Mitochondria, Liver/physiology , Mitochondrial Swelling/drug effects , NADP/metabolism , Piperazines/therapeutic use , Protective Agents/therapeutic use , Rats , Rats, Wistar , Reperfusion Injury/pathology , Reperfusion Injury/prevention & control
8.
Ann Pharm Fr ; 59(3): 211-4, 2001 May.
Article in French | MEDLINE | ID: mdl-11427823

ABSTRACT

We studied the antihypertension action of Herniaria glabra saponins and compared the effect with that of furosemide. Spontaneously hypertensive rats were treated with H. glabra saponins at a dosage of 200mg/Kg of body weight. Treatment led to progressive decline in both systolic and diastolic blood pressures. After one month of therapy, pressures were: 141,60+/-7,51 / 90,40+/-5.46mmHg versus 187,60+/-5,94/119,10+/-7.79mmHg (p<0,001). We did not observe any change in heart rate. H. glabra saponins were able to lower blood pressure by a multifactorial mechanism.


Subject(s)
Antihypertensive Agents/pharmacology , Hypertension/drug therapy , Plants, Medicinal/chemistry , Saponins/pharmacology , Animals , Antihypertensive Agents/toxicity , Blood Pressure/drug effects , Female , Heart Rate/drug effects , Hypertension/genetics , Male , Nifedipine/therapeutic use , Rats , Rats, Inbred SHR , Saponins/toxicity
10.
Reprod Nutr Dev ; 41(5): 393-9, 2001.
Article in French | MEDLINE | ID: mdl-12014366

ABSTRACT

The diuretic activity of an infusion of Lavandula officinalis was studied in the Wistar rat. Thus, the kinetics of hydroelectrolytic elimination in response to the oral administration of an infusion of pharmaceutical lavender flowers were measured in the rats. Experiments were completed under similar conditions using a synthetic pharmacological diuretic, Diamox. The aqueous extract of this aromatic plant accelerated the elimination of the water overload. At the peak of the diuretic response, urinary osmolarity was significantly less than that of controls (111+/-14 vs. 195+/-11 mosmol x kg(-1)). Sodium excretion was moderate following administration of the infusion when compared to the synthetic diuretic. The stability of the aldosterone concentrations in the plasma and the absence of correlation with plasma sodium concentrations, coupled with the observed clearance of the free water (0.055+/-0.007 vs. 0.045+/-0.012 mL x min(-1)) show that the increase in diuresis and the moderate increase in sodium excretion are of tubular origin. The result of the phytochemical analysis of hexane extracts in the infusion and in urine indicated that four or five chemical factors may be involved in the diuretic effect of lavender.


Subject(s)
Diuretics/pharmacology , Lavandula/chemistry , Plant Extracts/pharmacology , Acetazolamide , Administration, Oral , Aldosterone/blood , Animals , Diuretics/pharmacokinetics , Female , Osmolar Concentration , Plant Extracts/pharmacokinetics , Rats , Rats, Wistar , Urinalysis/veterinary
11.
Therapie ; 56(5): 569-74, 2001.
Article in French | MEDLINE | ID: mdl-11806295

ABSTRACT

Clamping the hepatic pedicle (or Pringle's manoeuvre) is frequently used to reduce blood loss during liver surgery. This induces a normothermic ischaemia of the overall liver. In this study we have investigated the anti-ischaemic effect of trimetazidine during surgery on hydatid cysts of the liver requiring vascular clamping of the hepatic pedicle. Seventy-six hepatic pericystectomies were performed under a 40 min normothermic ischaemia. Two randomized groups including 38 patients each received daily either trimetazidine (80 mg/kg, group 1) or placebo (group 2) for 5 days before surgery. The effect of trimetazidine was evaluated on different parameters, the macroscopic appearance of the tissue, the ATP content in liver biopsies obtained before and after 15, 30 and 60 min reperfusion, the activity of the aminotransferase in the plasma and the plasma concentrations of reduced and oxidized gluthatione. No mortality was observed. The duration of hospital stay was reduced for patients treated with trimetazidine (8 +/- 1 days compared with 11 +/- 1.5 days for patients in group 2; p < 0.05). Morbidity rate was lower in group 1 (11 per cent) than in group 2 (18.5 per cent) but the decrease was not significant. Trimetazidine treatment reduced cytolysis (p < 0.05 on day 1, day 3, day 5), increased liver ATP content and limited the increase of reduced and oxidized gluthatione in the plasma during reperfusion. These results suggest that trimetazidine alleviates ischaemia-reperfusion injury during liver surgery and may allow extension of the ischaemic period without damage to the liver.


Subject(s)
Liver/surgery , Reperfusion Injury/prevention & control , Surgical Instruments , Trimetazidine/therapeutic use , Vasodilator Agents/therapeutic use , Adult , Echinococcosis, Hepatic/surgery , Female , Humans , Intraoperative Care , Male , Middle Aged
12.
Eur J Pharmacol ; 406(2): 281-92, 2000 Oct 13.
Article in English | MEDLINE | ID: mdl-11020492

ABSTRACT

The protective effect of N-[(3, 5-di-tertiobutyl-4-hydroxy-1-thiophenyl)]-3-propyl-N'-(2,3, 4-trimethoxybenzyl)piperazine (S-15176) on liver injury induced by warm ischemia-reperfusion was investigated using a rat model. Animals were subjected to 2 h of ischemia followed by different reperfusion times. Hepatocyte integrity was assessed by measuring plasma alanine and aspartate aminotransferase activities, and by determining reduced and oxidized glutathione in plasma and bile. Hepatocyte function was quantitated by determining bile flow and liver ATP content. Ischemia-reperfusion resulted in severe hepatic injury involving a huge increase in alanine and aspartate aminotransferase activities, a drop in ATP content, and a decrease in bile flow. Plasma and bile reduced (GSH) and oxidized (GSSG) glutathione concentrations were inversely related: plasma levels increased when biliary levels decreased. This was associated with a decrease in animal survival (-34%). S-15176 pretreatment (1.25, 2.5, 5 or 10 mg kg(-1) day(-1)) improved the survival rate and limited tissue damages in a dose-dependent manner. The pretreatment also reduced the aminotransferase leakage from hepatocytes and the increase in plasma glutathione levels. In addition, normalization of the plasma GSSG/GSH ratio, a good index of an oxidative stress, was observed in groups treated with the higher dosage, suggesting that the antioxidant properties demonstrated for the compound in vitro (IC(50)=0.3 microM towards lipid peroxidation) could play a role in its protective effect. S-15176 pretreatment also protected the organ from the drop in ATP levels. At the higher dose, ATP content was maintained at a level almost 86% of the sham-operated group after 60 min of reperfusion. This was associated with a restoration of the biliary flow. These data suggest that S-15176 may be a useful drug in liver surgery to prevent ischemia-reperfusion injury.


Subject(s)
Antioxidants/pharmacology , Ischemia/drug therapy , Liver/blood supply , Piperazines/pharmacology , Reperfusion Injury/prevention & control , Adenosine Triphosphate/metabolism , Animals , Bile/drug effects , Dose-Response Relationship, Drug , Glutathione/metabolism , Glutathione Disulfide/metabolism , Liver/drug effects , Liver/metabolism , Male , Rats
13.
Therapie ; 55(3): 375-8, 2000.
Article in French | MEDLINE | ID: mdl-10967715

ABSTRACT

The chronic ingestion of 5 ml/kg/d of Argan oil by spontaneously hypertensive rats restores normal blood pressure and induces hypocholesterolaemia. In order to confirm these results Meriones shawi, a rodent of the Gerbillideae family, was tested as a second animal model. Meriones submitted to a hypercaloric diet and physical inactivity became fat, and exhibited hypertension, dyslipidaemia and hyperinsulinaemia. When treated for two months with the same dosage regimen, decreases in glycaemia, total plasmatic cholesterol, LDL, insulinaemia and systolic and diastolic blood pressures of 4.4 per cent, 14.4 per cent, 32.5 per cent, 26.8 per cent, 28.8 per cent and 30.5 per cent were simultaneously observed. Increases in LDH and of TG of 27.9 per cent and 16.2 per cent respectively were also observed. No effect on body weight occurred. The action of polyunsatured fatty acids of the Argan oil is predominant, but in addition, other constituents play an active part.


Subject(s)
Anticholesteremic Agents/pharmacology , Antihypertensive Agents/pharmacology , Plant Oils/pharmacology , Animals , Gerbillinae , Lipids/blood , Plants, Medicinal
14.
Therapie ; 55(3): 379-82, 2000.
Article in French | MEDLINE | ID: mdl-10967716

ABSTRACT

Nigella sativa (ranunculaceae) is used in Arab folk medicine as a diuretic and hypotensive plant. We report here the diuretic and hypotensive effects of dichloromethane extract of Nigella sativa seeds in the spontaneously hypertensive rat (SHR). An oral dose of Nigella sativa extract (0.6 ml/kg/day) and furosemide (5 mg/kg/day) increased significantly the diuresis by 16 and 30 per cent respectively after 15 days of treatment; urinary excretion of Cl-, Na+, K+ and urea is also increased. Simultaneously, the mean arterial pressure decreased respectively by 22 and 18 per cent in the Nigella sativa treated rat and nifédipine treated rat (0.5 mg/kg/day). In conclusion, the diuretic activity observed in the SHR rat treated with Nigella sativa seeds may be partially responsible for its diuretic action; it seems that other pathways may also be involved in their cardiovascular effects.


Subject(s)
Antihypertensive Agents/pharmacology , Diuretics/pharmacology , Plants, Medicinal/chemistry , Animals , Antihypertensive Agents/toxicity , Blood Pressure/drug effects , Diuresis/drug effects , Diuretics/toxicity , Medicine, Arabic , Mice , Plant Extracts/pharmacology , Plant Extracts/toxicity , Rats , Rats, Inbred SHR
15.
Fitoterapia ; 71(1): 50-4, 2000 Feb.
Article in English | MEDLINE | ID: mdl-11449470

ABSTRACT

The alkaloidic fraction of the methanol extract of Peganum harmala seeds was tested in vitro on three tumoral cell-lines: UCP-Med and Med-mek carcinoma, and UCP-Med sarcoma. Proliferation was significantly reduced at all tested concentrations (20-120 micrograms/ml) during the first 24 h of contact. A cell lysis effect occurred after 24 h and increased thereafter to complete cell death within 48-72 h, depending on tested concentration.


Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Neoplasms, Experimental/prevention & control , Plants, Medicinal , Rosales , Alkaloids/therapeutic use , Animals , Antineoplastic Agents, Phytogenic/therapeutic use , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Male , Phytotherapy , Plant Extracts/pharmacology , Rats , Rats, Wistar , Seeds , Tumor Cells, Cultured/drug effects
16.
Pharmacol Res ; 39(3): 211-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10094846

ABSTRACT

Ischaemia-reperfusion induces structural and functional damage to hepatocytes. The purpose of this study was to evaluate the protective effect of trimetazidine, an anti- ischaemic drug, in a rat liver model of ischaemia-reperfusion. Male Wistar rats were divided into groups pretreated with different doses of trimetazidine (1, 5, 10 or 20 mg kg-1 day-1) or saline for 7 days. Liver ischaemia was induced for 120 min and blood reflow was subsequently restored for 30, 60, 90 or 120 min. The activities of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) as well as the bile flow and the liver ATP content were determined. Ischaemia-reperfusion induced major alterations of hepatic functions involving increases of ASAT and ALAT activities, a drop of ATP content and a sharp decrease in bile flow. Trimetazidine pretreatment reduced the liver injury. Indeed, it lowered the increase in ALAT and ASAT activities observed immediately after reperfusion and maintained higher concentrations of hepatic ATP. Simultaneously, bile flow was increased. These effects were dose-dependent and 5 mg kg-1 day-1 seemed to be the lowest effective dose. In this experimental model trimetazidine pretreatment reduced the liver damage induced by ischaemia-reperfusion. Our data suggest that trimetazidine may be a useful drug in liver surgery to prevent ischaemia-reperfusion injury.


Subject(s)
Liver Diseases/prevention & control , Protective Agents/therapeutic use , Reperfusion Injury/prevention & control , Trimetazidine/therapeutic use , Animals , Male , Rats , Rats, Wistar
17.
Therapie ; 54(6): 735-9, 1999.
Article in English | MEDLINE | ID: mdl-10709449

ABSTRACT

Experiments were performed on male and female spontaneously hypertensive rats weighing 310-340 g (10 animals per group). The oral administration of 200 mg/kg/day of saponins from Herniaria glabra for 30 days, resulted in a significant decrease in blood pressure in hypertensive rats. The systolic and diastolic blood pressure decreased significantly and respectively from 187.60 +/- 20.63/119.00 +/- 7.09 mmHg at day 0 (D0) to 141.60 +/- 7.51/90.40 +/- 7.68 mmHg at day 30 (D30), p < 0.001 (vs. 186.30 +/- 11.27/114.10 +/- 12.00 mm Hg at D0 to 154.50 +/- 6.38/132.3 +/- 7.68 mmHg at D30 in furosemide-treated group, p < 0.001). Control animals receiving placebo did not show any significant variation in the mean arterial pressure. The effect of saponins of Herniaria glabra on renal function was evaluated in spontaneously hypertensive rats using clearance techniques. Glomerular filtration rate was constant in the control rats and increased significantly in the hypertensive rats after saponins treatment (5.55 +/- 0.32 vs. 6.03 +/- 0.43 ml.min-1.kg-1 in the control (C) and saponins (S) groups, respectively, p < 0.05). Saponins administration provoked an increase in urinary flow (59.38 +/- 5.85 ml.kg-1.24 h-1 vs. 36.92 +/- 5.17 ml.kg-1.24 h-1, p < 0.001). Saponins also increased potassium excretion (6.89 +/- 0.81 mmol.kg-1.24 h-1 vs. 5.40 +/- 0.51 mmol.kg-1.24 h-1, p < 0.001) and sodium excretion (10.74 +/- 1.21 mmol.kg-1.24 h-1 vs. 7.25 +/- 0.54 mmol.kg-1.24 h-1, p < 0.001) as well as chloride excretion (13.59 +/- 1.04 mmol. kg-1.24 h-1 vs. 9.67 +/- 0.77 mmol.kg-1.24 h-1, p < 0.001). It is concluded that chronic oral administration of saponins from Herniaria glabra decreased the arterial blood pressure and affected salt and water transport in renal tubules.


Subject(s)
Hypertension/drug therapy , Kidney/drug effects , Plants, Medicinal/chemistry , Saponins/therapeutic use , Animals , Blood Pressure/drug effects , Diuresis/drug effects , Drug Evaluation, Preclinical , Female , Furosemide , Glomerular Filtration Rate/drug effects , Male , Morocco , Natriuresis/drug effects , Rats , Rats, Inbred SHR , Saponins/isolation & purification , Saponins/pharmacology
18.
Therapie ; 54(6): 753-8, 1999.
Article in English | MEDLINE | ID: mdl-10709452

ABSTRACT

From ancient times, Peganum harmala was claimed to be an important medicinal plant. Its seeds were known to possess hypothermic, and essentially hallucinogenic properties. Various authors have undertaken studies on the antibacterial, antifungal and antiviral effects of Peganum harmala seeds, but studies on the antitumour activity are not to be found in the literature. In Moroccan traditional medicine, seed powder is sometimes used on skin and subcutaneous tumours. This work was designed to investigate some aspects of the antineoplastic properties of the plant Peganum. Varying concentrations (10 to 120 micrograms/ml) of total alkaloid extracts of Peganum harmala seeds (collected in Morocco) were tested in vitro on four tumoural cell-lines: Med-mek and UCP-Med carcinoma, UCP-Med sarcoma and Sp2/O-Ag14. In vivo experiments were performed with the Sp2/O cell-line grafted subcutaneously in syngenic BALB/c mice. In vitro, proliferation of tumoural cell lines was significantly reduced by all tested concentrations of the Peganum alkaloid extracts during the first 24 h of contact. A cell lysis effect occurred after 24 h and progressed to complete cell death within 48 to 72 h depending on the alkaloid concentration. Results obtained indicate that alkaloids of Peganum have a high cell toxicity in vitro. The active principle at a dose of 50 mg/kg given orally to mice for 40 days was found to have significant antitumoural activity. Peganum harmala alkaloids thus possess significant antitumour potential, which could prove useful as a novel anticancer therapy.


Subject(s)
Alkaloids/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Neoplasms, Experimental/drug therapy , Plants, Medicinal/chemistry , Alkaloids/pharmacology , Alkaloids/therapeutic use , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Cyclophosphamide/therapeutic use , Drug Screening Assays, Antitumor , Fibrosarcoma/drug therapy , Liver Neoplasms, Experimental/drug therapy , Mice , Mice, Inbred BALB C , Morocco , Multiple Myeloma/drug therapy , Neoplasm Transplantation , Phytotherapy , Rats , Rats, Wistar , Seeds/chemistry , Tumor Cells, Cultured/drug effects
19.
J Pharmacol Exp Ther ; 286(1): 23-8, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9655837

ABSTRACT

Recent studies suggest a crucial role played by mitochondria in the pathogenesis of ischemia-reperfusion injury. This study was conducted to clarify the role of trimetazidine, a cellular anti-ischemic agent, on mitochondria isolated from rat liver subjected to 120-min normothermic ischemia followed by 30-min reperfusion. Rats were divided into groups, pretreated with different doses of trimetazidine (5, 10 and 20 mg/kg/day) or saline and subjected to the ischemia-reperfusion process; another group served as the sham-operated controls. Alanine aminotransferase and aspartate aminotransferase activities and hepatocyte ATP content, bile flow and mitochondrial functions were assessed. Ischemia-reperfusion caused membrane leakage from hepatocytes and a decrease in ATP content and in bile flow. These effects were well correlated with alterations in mitochondrial function, namely, decrease in ATP synthesis, NAD(P)H level and mitochondrial membrane potential and generation of mitochondrial permeability transition. The pretreatment of rats with trimetazidine prevented these ischemia-reperfusion deleterious effects at both the cellular and mitochondrial level in a dose-dependent manner. It is concluded that trimetazidine at an optimal dosage of 10 mg/kg/day protects mitochondria against the deleterious effects of ischemia-reperfusion. This protective effect appears to be the key factor through which this drug exerts its cytoprotective activity.


Subject(s)
Ischemia/metabolism , Liver/blood supply , Mitochondria, Liver/drug effects , Reperfusion Injury/metabolism , Trimetazidine/pharmacology , Vasodilator Agents/pharmacology , Adenosine Triphosphate/biosynthesis , Animals , Liver/drug effects , Male , Membrane Potentials/drug effects , Mitochondria, Liver/metabolism , Mitochondrial Swelling/drug effects , NAD/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species
20.
Therapie ; 52(2): 151-4, 1997.
Article in French | MEDLINE | ID: mdl-9231511

ABSTRACT

The use of cyclosporin A is often limited by its nephrotoxicity. This dose-dependent toxicity can occur in all kinds of transplantation and is reversed with drug withdrawal. Cyclosporin A induces a vasoconstriction leading to an increase of renal vascular resistance and a reduction of glomerular filtration. Histochemical studies show mitochondrial alterations and an excess of cytosolic and mitochondrial calcium leading to a decrease of ATP synthesis. Two strategies can be evoked for limiting cyclosporin-A-induced nephrotoxicity. First, the use of drugs counteracting the vasoconstriction has been proposed. Second, drugs acting by restoration of ATP synthesis could also be of interest. For example, calcium channel blockers may be used for limiting the Ca2+ fluxes into cells. Another way to protect ATP synthesis is to inhibit the cyclosporin-A-induced increase of mitochondrial Ca2+ concentrations; Trimetazidine has shown its efficiency in vitro for protecting mitochondria against these modifications of Ca2+ homeostasis and is under clinical evaluation.


Subject(s)
Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Animals , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Organ Transplantation
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