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PubMed1996

Effects of Ginkgo biloba extract and preconditioning on the diabetic rat myocardium.

Effects of preconditioning and Ginkgo biloba extract (EGb 761) were studied in isolated nondiabetic and diabetic ischaemic and re-perfused rat hearts. Hearts were randomly divided into five groups in both the age-matched non-diabetic and the 8-week streptozotocin-induced diabetic groups: Group I, hearts were subjected to 30 min of global ischaemia followed by 30 min of re-perfusion; Group II, one cycle of preconditioning consisting of 5 min ischaemia and 10 min re-perfusion before the induction of 30 min of ischaemia and 30 min of re-perfusion; Group III, two cycles of preconditioning; Group IV, three cycles; and Group V, four cycles before the onset of 30 min ischaemia followed by 30 min of re-perfusion. Four cycles of ischaemic preconditioning resulted in a reduction of arrhythmias in non-diabetic rats. Thus, in non-diabetics, the incidence of ventricular fibrillation and tachycardia fell from 92% and 100% (no preconditioning) to 33% (p < 0.05) and 42% (p < 0.05), respectively. Four cycles of preconditioning failed to reduce the incidence of re-perfusion arrhythmias in diabetic subjects. Preconditioning reduced the formation of oxygen free radicals measured by electron spin resonance spectroscopy, but the recovery of cardiac function was low in all non-diabetic and diabetic preconditioned groups. EGb 761 at 25 and 50 mg/kg improved cardiac function in non-preconditioned and preconditioned non-diabetic and diabetic hearts. During re-perfusion in the four-cycle preconditioned non-diabetic and diabetic groups, the amount of free radicals was reduced approximately by 50 and 70% using 25 and 50 mg/kg of EGb 761, respectively. EGb 761 improved cardiac function after ischaemia in both non-preconditioned and preconditioned non-diabetic and diabetic rats. Our data suggest that diabetes could abolish the precondition-induced protection.

Animals↗
PubMed1999

[The evaluation by video capillaroscopy of the efficacy of a Ginkgo biloba extract with L-arginine and magnesium in the treatment of trophic lesions in patients with stage-IV chronic obliterating arteriopathy].

BACKGROUND AND AIMS: This study aimed to evaluate the influence of Ginkgo biloba extract with arginine and magnesium used for the treatment of trophic lesions in the lower limbs caused by both diabetic and non-diabetic microangiopathy. METHODS: A comparative study was carried out in 20 patients who were divided into two groups: 10 were treated with ASA plus Ginkgo biloba extract with arginine and magnesium and 10 with ASA plus conventional hemorheology. The observation time was extended to 6 months, taking into consideration patients with trophic lesions to the lower limbs suffering from diabetic and non-diabetic peripheral arterial occlusive disease. The evaluation was performed by clinical, ultrasonographic and perilesional video capillaroscopy monitoring. Ultrasonographic and video capillaroscopy instrumental methods were used because they provide a full picture of macro and microcirculatory conditions around lesions. RESULTS: The study showed the undoubted efficacy of Ginkgo biloba extract with magnesium and arginine in relation to the following points: reduced healing times for the trophic lesion compared to the control group, improved painful symptoms, increased perilesional neoangiogenesis. No significant differences were observed from a Doppler ultrasonographic point of view or with regard to the claudication free interval. CONCLUSIONS: Ginkgo biloba extract with arginine and magnesium can improve the dynamics of cutaneous trophism in lesions caused by diabetic and non-diabetic microangiopathy.

Aged↗
PubMed2000

Ginkgo biloba extract for the treatment of intermittent claudication: a meta-analysis of randomized trials.

PURPOSE: The optimal treatment of intermittent claudication has not yet been identified. Ginkgo biloba extract has been reported to have beneficial effects. We performed a meta-analysis of the efficacy of Ginkgo biloba extract for intermittent claudication based on the results of randomized, placebo-controlled, double-blind trials. METHODS: Literature searches of MEDLINE, EMBASE, BIOSIS, AMED, CISCOM, and the Cochrane Library were performed to identify studies on the topic. Manufacturers of commercial Ginkgo biloba products and authors of original publications and reviews were contacted to provide additional information. No language restrictions were imposed. RESULTS: Eight randomized, placebo-controlled, double-blind trials were included. Meta-analysis found a significant difference in the increase in pain-free walking distance in favor of Ginkgo biloba (weighted mean difference: 34 meters, 95% confidence interval [CI]: 26 to 43 meters). In studies using similar methodological features (ergometer speed: 3 km/h, inclination: 12%) this difference was 33 meters in favor of Ginkgo biloba (95% CI: 22 to 43 meters). Adverse effects were rare, mild, and transient. CONCLUSIONS: These results suggest that Ginkgo biloba extract is superior to placebo in the symptomatic treatment of intermittent claudication. However, the size of the overall treatment effect is modest and of uncertain clinical relevance.

Double-Blind Method↗
PubMed2004

Ginkgo biloba extract (Egb 761) inhibits beta-amyloid production by lowering free cholesterol levels.

Ginkgo biloba extract (EGb 761) can improve cognitive function in patients with Alzheimer's disease, but the molecular mechanisms underlying this effect remain undefined. Because free cholesterol may be involved in the production of beta-amyloid precursor protein and amyloid beta-peptide, key events in the development of Alzheimer's disease, we examined EGb 761 in relation to cholesterol and amyloidogenesis. In aging rats, EGb 761 treatment lowered circulating free cholesterol and inhibited the production of brain beta-amyloid precursor protein and amyloid beta-peptide. Exposure of PC12 cells to EGb 761 decreased the processing of beta-amyloid precursor protein and abolished cholesterol-induced overproduction of this protein. Exposure of human NT2 cells to EGb 761 decreased free cholesterol influx and increased free cholesterol efflux. Our findings indicate that free circulating and intracellular cholesterol levels affect the processing of beta-amyloid precursor protein and amyloidogenesis. Our findings also provide the first demonstration that EGb 761 can influence these mechanisms.

Aging↗
PubMed2002

Molecular and cellular assessment of ginkgo biloba extract as a possible ophthalmic drug.

We have investigated the biochemical and cell biological basis of the reported beneficiary effects of the leaf extracts of the plant Ginkgo biloba, which has been used as a possible ophthalmic drug. The antioxidant, antimicrobial, anti-apoptotic and cytoprotective properties of the standardized extract called EGb761 were assayed. Chemical stresses were induced in cells using alloxan or dexamethasone, and the effect of EGb761 on them was studied using the MTT and TUNEL assays. Its ability to modulate the activities of some antioxidant enzymes was tested in vitro. In addition, cataract was induced in rats through selenite injection, and the effect of EGb761 administration on the progression of cataract was studied using slit lamp examination. Ginkgo biloba was found to be an excellent antioxidant. It readily scavenges reactive oxygen and nitrogen radicals and inhibits oxidative modifications that occur to proteins in vitro. It enters intact cells and protects them from alloxan-mediated and light-mediated stress, and the nuclear DNA from single strand breaks. It also effectively inhibits chemically induced apoptosis. It does not modulate the activities of endogenous antioxidant enzymes, nor does it have any significant antimicrobial activity. Unlike some other plant extracts, it is not phototoxic. In experiments wherein selenite cataract was induced in laboratory rats, treatment with the extract significantly retards the progression of lens opacification in vivo. Ginkgo biloba's inherent antioxidant, antiapoptotic and cytoprotective action and potential anticataract ability appear to be some of the factors responsible for its beneficial effects.

Animals↗
PubMed2006

Effects of Ginkgo biloba extract feeding on salt-induced hypertensive Dahl rats.

We previously demonstrated that Ginkgo biloba extract (GBE) produced vasodilation via the nitric oxide synthesis and release by increasing the intracellular calcium level in vascular endothelial cells of rats. The present study aimed to clarify the effects of dietary administration of GBE on the blood pressure and vascular tone of hypertensive Dahl salt-sensitive (Dahl) rats in order to evaluate its therapeutic actions and availability. Dahl rats were fed an 8.0% NaCl diet or an 8.0% NaCl plus 0.5% GBE diet for 24 d. The feeding of GBE did not change the heart rate, but significantly decreased systolic blood pressure. After 24 days' administration, the effects of GBE on the atria and aorta isolated from Dahl rats were examined. The GBE-containing diet did not affect the negative and positive actions of isolated atria that were produced by acetylcholine and isoproterenol, respectively. In the aortic preparations, the relaxation in response to acetylcholine was significantly potentiated by a GBE-containing diet. Sodium nitroprusside-induced relaxation was unchanged by GBE-containing diet. These results demonstrated that GBE reduced salt-related elevation of blood pressure and restored the impaired acetylcholine-induced vasodilation in aortic segments.

Acetylcholine↗
PubMed1994

Effects of repeated treatments with an extract of Ginkgo biloba (EGb 761), bilobalide and ginkgolide B on the electrical activity of pancreatic beta cells of normal or alloxan-diabetic mice: an ex vivo study with intracellular microelectrodes.

1. The effects of repeated (5-day) treatments with an extract of Ginkgo biloba leaves (EGb 761), bilobalide, and ginkgolide B on the in vitro electrical activity of insulin-secreting pancreatic beta cells of mice have been examined using intracellular microelectrodes. 2. EGb 761 (200 mg/kg/day, p.o.) protected beta cells against the toxic effects of alloxan (50 mg/kg, i.v.), an effect characterized by a restoration of membrane potential (Vr) and an increase in spike frequency (Fs/30), an indicator of insulin secretion. 3. Treatment of non-diabetic mice with EGb 761 (200 mg/kg/day, p.o.) increased Fs/30 of their beta cells, as tested by in vitro exposure of the cells to 11.1 mM glucose, an effect that also occurred with bilobalide (8 mg/kg/day, i.p.) but not with ginkgolide B (4 mg/kg/day, i.p.). 4. Since bilobalide and ginkgolide B caused opposite effects on the sensitivity of beta cells to glucose, the stimulatory effect of EGb 761 on Fs/30 may be attributed to its content of bilobalide. 5. In contrast to its ex vivo effect, the direct in vitro effect of EGb 761 (10 and 25 micrograms/ml) on beta cells favors a decrease in electrical activity, indicating that its in vivo action might be indirect (e.g. via the formation of an active metabolite).

Action Potentials↗
PubMed2006

Sustained neuroprotection and facilitation of behavioral recovery by the Ginkgo biloba extract, EGb 761, after transient forebrain ischemia in rats.

The effects of the Ginkgo biloba extract, EGb 761, on ischemia-induced learning/memory impairments and hippocampal damage were evaluated in a non-food motivated, aversive radial maze task (AvRM). Rats were subjected to 15 min transient, global cerebral ischemia (TGCI). In the first experiment, rats were rendered ischemic, and 23 days later were tested for acquisition performance (post-operative training). In a second experiment, rats were trained for 10 days and then subjected to ischemia (pre-operative training); the retention of cognition performance was assessed on days 31, 35 and 39 after ischemia. Acquisition and retention performances were expressed by (a) latency to find a goal box, (b) number of reference memory errors, and (c) number of working memory errors. EGb 761 (50 or 150 mg/kg) was given orally, starting before ischemia and continuing for up to 3 days after ischemia. TGCI markedly disrupted both acquisition and retention performance (p < 0.001-0.05). EGb 761 (150 mg/kg) completely reversed acquisition impairment as measured by the parameters 'latency' and 'number of reference errors' when performance was examined across sessions (p < 0.01-0.05). The total number of reference errors was also completely abolished by EGb 761 (150 mg/kg). However, EGb 761 did not statistically reduce the effects of TGCI on the parameter 'working memory errors' (across session and total). At 50 mg/kg, EGb 761 did not affect ischemia-induced acquisition impairment at all. The retention deficit caused by ischemia was not statistically reduced by EGb 761 (150 mg/kg), whatever examined across session or as total. EGb 761 reduced the extent of hippocampal CA1 cell loss (p < 0.01-0.001), an effect sustained at least up to 40 days after ischemia. These findings show that EGb 761 is effective in reducing, at least partially, both the cognitive impairments and hippocampal damage after TGCI in rats, and suggest that its effect on behavioral recovery may be dissociated from the neuroprotective effect on the hippocampus. The present results also validate the AvRM as an alternative, reliable behavioral test to assess the effects of drugs on behavioral recovery after ischemic brain damage.

Analysis of Variance↗
PubMed2001

Chemopreventive effect of Ginkgo biloba extract against benzo(a)pyrene-induced forestomach carcinogenesis in mice: amelioration of doxorubicin cardiotoxicity.

Ginkgo biloba extract (EGb) is a natural product that possesses antioxidant and anticlastogenic properties. The current study was conducted to investigate the effect of EGb on benzo(a)pyrene (BP)-induced forestomach neoplasia, and to explore its possible beneficial effects against doxorubicin (Dox)-induced cardiotoxicity. Tumor was induced in female Swiss albino mice by oral administration of 1 mg BP, twice weekly for four weeks. EGb was given, at a daily oral dose of 150 mg kg(-1), two weeks before and during BP administration. Dox was given ip at a dose of 1.5 mg kg(-1), once weekly, for four weeks, during BP administration. EGb and Dox were given as combined or monotherapies. Results of the present investigation revealed that EGb blunted forestomach tumor multiplicity, as compared to control tumor bearing group. It also exhibited high activity to induce cytosolic glutathione S-transferase and glucose-6-phosphate dehydrogenase (G6PDH) in liver, as well as replenished hepatic glutathione that have been inhibited or depleted by tumorigenesis. Furthermore, it normalized nitric oxide (NO) serum level, without any observed alteration in neither the activity of liver microsomal NADPH-cytochrome P-450 reductase nor serum level of tumor necrosis factor-alpha (TNFalpha). Similar results have been obtained with Dox, but it failed to affect G6PDH activity, while increased serum TNFalpha and NO levels. The combined therapy did not add further to the anticarcinogenic effect of Dox, however it succeeded in ameliorating the deleterious effects of Dox on the heart; as evidenced by the reduction of cardiac lipoperoxidation, with modulation of Dox-induced pathological changes. Therefore, EGb confers a beneficial chemopreventive effect against BP-induced gastric carcinogenesis in mice, and possesses a salutary ameliorating potential on the cardiotoxic effects of Dox.

Animals↗
PubMed2005

[Study on the effect of Ginkgo biloba extract on the tension of diabetic rat artery].

OBJECTIVE: To investigate the effect and possible mechanism of Ginkgo biloba extract EGB50 on vascular tension of type II diabetes mellitus (DM) induced by hyperglycemia and hyperlipidemia. METHODS: Rats were randomly divided into normal control rats (Control), diabetic rats (DM), diabetic rats oral-treated with higher dose Ginkgo biloba extract EGB50 (H) and diabetic rats treated with lower dose EGB50 (L). The serum levels of Advanced Glycosylation end-products (AGEs), cholesterol (CHOL), triglyceride (TRIG) and superior mesenteric artery tension were quantified and measured. RESULTS: After 5 weeks' oral-treatment, serum CHOL, TRIG and AGEs increased, sustained phase of contractile response in high K+ solution and PD2 of phenylephine decreased in diabetic arteries. The biochemical indexes and the tension of vascular function had less significance in L group, but improved distinctly in EGB50 H group (decreasing rate in high K+ solution: 22.52 +/- 5.48%, vs DM:44. 19 +/- 11.03%, P < 0.05) (PD2 of PE: 6.15 +/- 0.22 vs DM: 6.62 +/- 0.13, P < 0.05). CONCLUSION: EGB50 is capable of reducing serum hyperlipidemia,the concentration of AGEs, thus it can reduce the impairment of the oxidants to endothelium cells of vessels and improve pathological and functional change of artery of diabetes.

Animals↗
PubMed2003

Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma.

OBJECTIVE: To evaluate the effect of Ginkgo biloba extract (GBE) on preexisting visual field damage in patients with normal tension glaucoma (NTG). DESIGN: Prospective, randomized, placebo-controlled, double-masked cross-over trial. PARTICIPANTS: Twenty-seven patients with bilateral visual field damage resulting from NTG. INTERVENTION: Patients received 40 mg GBE, administered orally, three times daily for 4 weeks, followed by a wash-out period of 8 weeks, then 4 weeks of placebo treatment (identical capsules filled with 40 mg fructose). Other patients underwent the same regimen, but took the placebo first and the GBE last. Visual field tests, performed at baseline and at the end of each phase of the study, were evaluated for changes. MAIN OUTCOME MEASURES: Change in visual field and any ocular or systemic complications. RESULTS: After GBE treatment, a significant improvement in visual fields indices was recorded: mean deviation (MD) at baseline versus MD after GBE treatment, 11.40 +/- 3.27 dB versus 8.78 +/- 2.56 dB (t = 8.86, P = 0.0001, chi-square test); corrected pattern standard deviation (CPSD) at baseline versus CPSD after GBE treatment, 10.93 +/- 2.12 dB versus 8.13 +/- 2.12 dB (t = 9.89, P = 0.0001, chi-square test). No significant changes were found in intraocular pressure, blood pressure, or heart rate after placebo or GBE treatment. Any ocular and systemic side effects were recorded for the duration of the trial. CONCLUSIONS: Ginkgo biloba extract administration appears to improve preexisting visual field damage in some patients with NTG.

Administration, Oral↗
PubMedDate not supplied

Ginkgo biloba extract (EGb 761) modulates bleomycin-induced acute lung injury in rats.

The effect of Ginkgo biloba extract (EGb 761) on bleomycin (BLM)-induced acute lung injury was studied in rats. The responsiveness of isolated pulmonary arterial rings to 5-hydroxytryptamine (5-HT) as well as the levels of some relevant biochemical markers in the lung tissue were taken as evidence for the acute lung injury. BLM was given intraperitoneally at a dose of 15 mg/kg/day for five consecutive days. It was found that BLM treatment attenuated the vasoconstrictor effect of 5-HT on the isolated pulmonary arteries. In lung tissues BLM also elevated the level of lipid peroxides and enhanced the activity of glutathione peroxidase. On the other hand, the level of glutathione and the activity of alkaline phosphatase were reduced. Body weight, lung weight and tissue glutathione-S-transferase activity were, however, not altered. Oral administration of EGb 761 at a dose of 100 mg/kg/day for five consecutive days did not alter any of the chosen biochemical parameters in the lung tissue except for a slight reduction in alkaline phosphatase activity. However, treatment with EGb 761 reduced the responsiveness of the pulmonary artery to 5-HT. Administration of EGb 761 (100 mg/kg/day; po) two hours prior to BLM (15 mg/kg/day; ip), for five consecutive days blunted the occurrence of further reduction in the vasoconstrictor response of the pulmonary artery to 5-HT. Furthermore, EGb 761 tended to normalize BLM-induced alterations in the measured biochemical markers in the lung tissue. The apparent modulatory influence of EGb 761 on BLM-induced acute lung injury stems, at least in part, from its beneficial free radical scavenging properties that provide the extract with antioxidant activity.

Animals↗
PubMedDate not supplied

[Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome].

The efficacy of standardized Ginkgo biloba extract (EGb 761) in treating congestive symptoms of premenstrual syndrome (PMS) was evaluated in a controlled multicentric double blind study versus placebo. The population studied was a group of 165 women aged between 18 to 45, in genital activity period, suffering since 3 cycles from congestive premenstrual troubles during at least 7 days per cycle. The characteristics of patients and PMS were the same in both groups (EGb 761 and placebo). The observation of one menstrual cycle confirmed the diagnosis of PMS. Then, during the 2 following cycles, each patient received either EGb 761 or placebo from the 16th day of the first cycle till the 5th day of the next cycle. A double evaluation of the symptoms was realized by the patient using a daily rating scale (auto-evaluation), by the practitioner during visits at the premenstrual phase before and after the two cycles treatment. From 165 patients included, 143 observations were available. With a good acceptability, EGb 761 was effective against the congestive symptoms of PMS, particularly breast symptoms with a statistical significance between EGb 761 and placebo. Neuropsychological symptoms were also improved. EGb 761 is an alternative of interest to therapeutics already used in treating PMS or can be associated without any inconvenience.

Adolescent↗
PubMed1990

Effects of an extract of Ginkgo Biloba (EGB 761) on "learned helplessness" and other models of stress in rodents.

The effects of repeated oral administration of an extract of Ginkgo Biloba (EGB 761) on various behavioral models of stress in rodents were investigated. The models in rats included "learned helplessness," shock-suppressed licking (Vogel conflict test) and forced swimming-induced immobility ("behavioral despair"). The models in mice included shock-suppressed exploration (four plates test), spontaneous exploration (staircase test) and food consumption in a novel situation (emotional hypophagia). Further tests in rats examined the effects of EGB 761 on memory (passive avoidance test) and responsiveness to shock to determine whether the preventive effects observed with EGB 761 in the learned helplessness procedure were due either to drug-induced impairment of memory or to reduced shock sensitivity. In all experiments EGB 761 was administered over 5 days at daily doses of 50 and 100 mg/kg PO. In some experiments (Vogel test, four plates test, staircase test, emotional hypophagia) the effects of acute administration were also investigated. The results showed that repeated administration of EGB 761 (50 and 100 mg/kg/day) before exposure to unavoidable shock (preventive treatment) clearly reduced the subsequent avoidance deficits in the learned helplessness procedure but was less effective when first administered after "helplessness" induction (curative treatment). EGB 761 did not affect performance in the passive avoidance task or alter the animals' response to electric shock, suggesting that the effects observed in the learned helplessness procedure were not due to impaired memory or reduced shock sensitivity. Anxiolytic-like activity was also seen in the emotional hypophagia test in mice where repeated administration of EGB 761 increased the amount of food consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Decreased electroconvulsive shock-induced diacylglycerols and free fatty acid accumulation in the rat brain by Ginkgo biloba extract (EGb 761): selective effect in hippocampus as compared with cerebral cortex.

The effect of Ginkgo biloba extract (EGb 761) treatment (100 mg/kg/day, per os, for 14 days) on electroconvulsive shock (ECS)-induced accumulation of free fatty acids (FFA) and diacylglycerols (DAG) was analyzed in rat cerebral cortex and hippocampus. EGb 761 reduced the FFA pool size by 33% and increased the DAG pool by 36% in the hippocampus. These endogenous lipids were unaffected in cerebral cortex. During the tonic seizure (10 s after ECS) the fast accumulation of FFA, mainly 20:4, was similar in sham- and EGb 761-treated rats, in both the cerebral cortex and hippocampus. However, further accumulation of free 18:0 and 20:4, observed in the hippocampus of sham-treated rats during clonic seizures (30 s to 2 min after ECS), did not occur in EGb 761-treated animals. The rise in DAG content triggered in the cortex and hippocampus by ECS was delayed by EGb 761 treatment from 10 s to 1 min, when values similar to those in sham animals were attained. Moreover, in the hippocampus the size of the total DAG pool was decreased by 19% during the tonic seizure. At later times, DAG content showed a faster decrease in EGb 761-treated rats. By 2 min levels of all DAG acyl groups decreased to values significantly lower than in sham animals in both cortex and hippocampus. This study shows that EGb 761 treatment affects, with high selectivity, lipid metabolism and lipid-derived second messenger release and removal in the hippocampus, while affecting to a lesser extent the cerebral cortex.

Animals↗
PubMed1998

Superoxide scavenging effect of Ginkgo biloba extract on serotonin-induced mitogenesis.

We have reported previously that serotonin (5-HT) stimulates the mitogenesis of bovine pulmonary artery smooth muscle cells (SMCs) through active transport of 5-HT and cellular signaling that includes elevation of superoxide (O2.-) and enhancement of protein tyrosine phosphorylation. Ginkgo biloba extract 501 (EGb 501), which has been demonstrated to act as an antioxidant, was found to block both the elevated O2.- and the proliferative and hypertrophic influences of 5-HT on SMCs, but not to directly inhibit the associated activation of NAD(P)H oxidase or the stimulation of phosphorylation of GTPase-activating protein (GAP). A similar effect of Ginkgo biloba extract 501 occurred on Chinese hamster lung fibroblasts (CCL-39), where 5-HT receptor, as opposed to transporter, action has been associated with mitogenesis. We conclude from these studies that Ginkgo biloba extract 501 quenches O2.- formation by 5-HT, thereby blocking its mitogenic effect. Stimulation of protein tyrosine phosphorylation of GAP by 5-HT appears to precede the elevation of O2.-.

Animals↗
PubMed2002

Effects of L-carnitine and ginkgo biloba extract (EG b 761) in experimental bleomycin-induced lung fibrosis.

The effects of Ginkgo biloba extract (EGb 761) and L-carnitine on bleomycin (BLM)-induced lung fibrosis were studied in rats. BLM (cumulative dose of 180 mgkg(-1)) was given intraperitoneally (i.p.) three times weekly for 4 consecutive weeks. Treatment with BLM enhanced the responsiveness of isolated pulmonary arterial rings to serotonin (5-HT), significantly increased the normal serum level of tumour necrosis factor (TNF-alpha) by approximately 105% and markedly elevated the level of lipid peroxide (LPO) and collagen content in the lung homogenates by 34 and 83%, respectively. EGb 761 (100 mgkg(-1) ), given in drinking water for the whole study period, totally abolished the BLM-induced alterations in the measured biochemical and pharmacological parameters. Meanwhile, L-carnitine (500 mg kg(-1) ), administered in drinking water, significantly decreased the BLM-induced elevations of serum TNF-alpha, LPO level in lung tissues and the enhanced responsiveness of pulmonary arterial rings to 5-HT. However,L-carnitine did not reduce the increase in the collagen content produced by BLM. The results of the present study indicate the beneficial effects of EGb 761 and L-carnitine against lung toxicity induced by BLM treatment. Furthermore, the present data shows the advantageous use of EGb 761 as a protective agent in BLM-induced lung fibrosis under the experimental circumstances.

Animals↗