Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice.
TL;DR: The hypothesis that prolonged Fen application induces dose-dependent increase in post-replication repair and caffeine enhanced toxicity by inhibiting repair process(es) is supported and the study suggests that Fen is a clastogen and since caffeine may have a synergistic effect, it should be avoided during treatment.
Abstract: Fenfluramine (Fen), an amphetamine-derivative widely used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice for assessing its clastogenic potentials. Concentrations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were administered orally for the study. Long-term treatment for 21 days showed dose-dependent significant increase in chromosomal aberrations on the 8th day. A significant decrease in aberration levels was seen in the late treatment period. Caffeine alone produced dose-and duration-dependent clastogcnicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given by gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares. The results support the hypouhesis that prolonged Fen application induces dose-dependent increase in post-replication repair and...
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TL;DR: Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity, which may be an additional burden in people using anorectic drugs.
Abstract: Context: Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approv...
13 citations
Cites background from "Potentiation by caffeine of the fre..."
...Its antigenotoxic (Geriyol et al., 2015; Sen et al., 1994), antioxidant (Zheng et al., 2004) and anticancer activities (Sabisz & Skladanowski, 2008) are well established....
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...On the contrary, Sen et al. (1994) reported that caffeine acted synergistically with another antiobesity drug-fenfluramine and increased chromosome aberrations over a period of time....
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...Its antigenotoxic (Geriyol et al., 2015; Sen et al., 1994), antioxidant (Zheng et al....
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TL;DR: It is concluded that the treatment of rats with D-fenfluramine modifies the metabolic balance of adipose tissue so as to direct glucose metabolism away from lipid synthesis and towards lactate production.
18 citations
TL;DR: The pregnancy had no effect on MMC- or CP-induced clastogenicity although a tendency to a decreased sensitivity to the damaging activity of MMC seemed to be detected in pregnant C57Bl mice compared to virgin female animals.
Abstract: Employing the micronucleus test in mouse bone marrow and in fetal mouse liver, the possible clastogenicity of caffeine as well as its influence on MMC- and CP-induced micronucleus levels were studied. The treatment of male and female C57Bl or BDF1 (C57Bl x DBA2) mice with caffeine (1 or 3 x 50 mg/kg and 100 mg/kg, s.c.) had no clastogenic effect in mouse bone marrow or in the fetal livers and maternal bone marrow when pregnant mice were injected with caffeine on day 16-17 of gestation. MMC (2.0 mg/kg, i.p.) increased up to 10-30-fold the number of MNPCEs in bone marrow compared to a 3-7 fold elevation of MNPCEs in fetal liver. A similar effect was also established in pregnant mice treated with CP (30 mg/kg, i.p.). No significant sex differences in spontaneous and MMC- or CP-induced MNPCEs levels were established in C57Bl and BDF1 mice. However, a significantly higher spontaneous rate of MNPCEs as well as a better-expressed responsiveness to the clastogenic activity of MMC and CP were established in C57Bl compared to BDF1 mice. The pregnancy had no effect on MMC- or CP-induced clastogenicity although a tendency to a decreased sensitivity to the damaging activity of MMC seemed to be detected in pregnant C57Bl mice compared to virgin female animals. The combined treatment of mice with caffeine (3 x 100 mg/kg) and MMC or CP caused an up to 45-49% potentiation of clastogenesis in the bone marrow of male, female and pregnant female C57Bl and BDF1 mice but not in fetal mouse livers.
11 citations
TL;DR: Fenfluramine is moderately clastogenic and a DNA damaging agent in vivo, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle.
Abstract: Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.
5 citations
TL;DR: It is shown that the caffeine-induced reduction of the survival of gamma-irradiated HeLa cells is reversed when Escherichia coli RecA protein is introduced into the cells with the aid of liposomes.
Abstract: It is confirmed that survival of γ-irradiated HeLa cells is decreased by post-treatment with caffeine. The caffeine effect is believed to be the result of an inhibition of the repair of γ-ray-induced DNA damage. In this work we show that the caffeine-induced reduction of the survival of γ-irradiated HeLa cells is reversed when Escherichia coli RecA protein is introduced into the cells with the aid of liposomes.
4 citations