Anticlastogenic effects of Ginkgo biloba extract (EGb 761) and some of its constituents in irradiated rats

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Abstract

In a previous study we reported that radiation-induced clastogenic factors (CF) are found in the plasma of Chernobyl accident recovery workers and that their chromosome damaging effects are inhibited by antioxidant treatment with a Ginkgo biloba extract (EGb761). In the present study, we induced CF in rats with a radiation dose of 4.5 Gy. The protective effects of the complete extract were compared to those obtained with the extract devoid of its terpene fraction (CP205), with isolated ginkgolides A+B and bilobalide at the concentrations present in EGb761. The pretreatment samples were taken at day 22 postirradiation, the posttreatment samples the day following arrest of the 3-week treatment. The adjusted clastogenic score (ACS) were reduced from 11.71±3.55 to 2.00±2.83 after treatment with 100 mg/kg and from 13.43±2.23 to 4.29±2.14 with 50 mg/kg of the complete extract (p<0.0001). Similar protective effects were observed with CP205, ginkgolides and bilobalide (p<0.001), while the reduction of ACS in placebo-treated rats was not statistically significant (12.80±1.79 and 9.20±2.68). However, if the efficacy of the treatment was compared to placebo, only the complete extract was significantly protective. While all components exerted anticlastogenic effects at the concentrations present in the complete extract, the comparison of the different groups by analysis of variance did not reveal significant differences. This may be due to to the small number of animals available in each treatment group. The complete extract reduced the ACS by 83% at the dose of 100 mg/kg, while the lower dose of 50 mg/kg and the three components reached only 66%–68% reduction. The better protection provided by the complete extract is due to synergistic rather than to additive effects.

Introduction

Chromosomal aberrations resulting from ionizing radiation are well documented. While a large body of evidence supports a direct effect of ionizing radiation on the chromosomes of exposed cells, several observations suggest indirect radiation effects due to the presence of plasma factors able of inducing chromosomal aberrations in unexposed cells. Such chromosomal breakage or clastogenic factors (CF) were first described in the plasma of patients, who had been irradiated accidentally [1]or therapeutically [2]. They were also observed in A-bomb survivors, where they persisted for many years after irradiation [3]. In a previous study, we reported that clastogenic activity was present in the plasma of Chernobyl accident recovery workers [4]and in children exposed to radiation as the consequence of this disaster [5]. We were also able to show that the damaging effects of these CF can be inhibited in vitro and in vivo by treatment with an extract from Ginkgo biloba leaves (EGb761) 6, 7. In the present study, we tried to determine which component of this extract was responsible for the protective effects. For this purpose, we choose an animal model, previously shown to respond to X-rays with CF formation [8].

Section snippets

Animals

Male Wistars rats (IFFA CREDO, Les Oncins France), 3 months of age were used for this study. They weighed approximately 400 g when they were irradiated.

Radiation exposure

Whole body irradiation was administered by a telecobalt unit to deliver a dose of 4.5 Gy in one fraction using two parallel opposed equally weighted lateral fields (8×8 cm at source axis distance, 80 cm).

Blood samples were taken on day 22 and 44 after irradiation and immediately centrifuged for plasma preparation. During the 3-week period

Results and discussion

The present study confirms the findings of Faguet et al. [8], who reported that the plasma of irradiated rats has clastogenic properties in cultures set up with blood of unexposed rats. The clastogenic activity was demonstrable immediately after irradiation, diminished therafter, but remained significantly increased until the end of their study period (10 weeks).

We studied a group of 14 animals at day 8 after irradiation and noted clastogenic activity in all samples, with a mean ACS of

Acknowledgements

We are grateful to Professor F. Baillet and the Department of Radiotherapy, La Pitié-Salpétrière Hospital, Paris, where the animals were irradiated.

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