Modification of cyclophosphamide-induced clastogenesis and apoptosis in rats by alpha-lipoic acid.

The aim of the present study was to investigate the protective efficacy of alpha-lipoic acid (LA) on the cyclophosphamide (CP)-induced chromosomal aberrations (CA) and apoptosis in the bone marrow of rats. Male Wistar rats of 140+/-20 g were categorized into eight groups. Five groups were administered CP (40 mg/kg body weight, intraperitoneally) to induce toxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to CP administration. A vehicle-treated control group and LA control groups were also included. Twenty-four hours after CP treatment, the frequency of CA in bone marrow cells were significantly increased in comparison with the controls. The CP-induced CA were associated with significant increase in DNA damage in the bone marrow as evidenced by increased single strand breaks, whereas in rats treated with LA and CP, the frequency of CA and single strand breaks were significantly decreased in comparison to those given CP alone. CP administration distinctly triggered the apoptotic and necrotic cell death, and LA pretreatment affected cell death by decreasing the number of apoptotic and necrotic cells. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage, indicating the dose dependent protective effect of LA. However, the protection by LA was not dependent on the time intervals between LA and CP administration. The results of this study illustrate the protective effect of LA on the CA and apoptosis induced by CP in the erythropoietic system of rats.

Salubrious effects of lipoic acid against adriamycin-induced clastogenesis and apoptosis in Wistar rat bone marrow cells.

Adriamycin (ADR), an anthracycline antibiotic, which is widely used as an antineoplastic drug in the treatment of various solid tumors, has been shown to induce genotoxicity in erythropoietic system. The aim of the present study was to investigate the protective efficacy of DL-alpha-lipoic acid (LA) on ADR-induced clastogenicity and apoptosis in the bone marrow of rats. The animals were randomly divided into eight groups consisting of six rats each. Five groups were administered ADR (20 mg/kg body weight, i.v.) to induce genotoxicity; four of these groups received a single intraperitoneal injection of LA at a dose of either 100 or 200 mg/kg body weight, and either 30 or 60 min prior to ADR administration. A vehicle treated control group and LA control groups were also included. The beneficial effects of LA were monitored by DNA strand breaks, chromosomal aberrations, micronucleus assay and apoptotic studies in the bone marrow cells of rats after 24 h following single dose of ADR treatment. ADR treatment caused significant clastogenicity and apoptosis in rat bone marrow cells. The treatment with LA showed significant reduction in the frequency of chromosomal aberrations, DNA strand breaks and apoptosis in bone marrow cells as well as decreased the micronuclei formation in bone marrow and peripheral blood of rats treated with ADR. The protective effect of LA was found to be stronger at a dose of 200 mg/kg body weight than 100 mg/kg body weight dosage with respect to the above results, indicating the dose dependent effect of LA. However, the protection by LA was not dependent on the time intervals between LA and ADR administration. The results of this study illustrate the protective effect of LA on ADR-induced clastogenicity and apoptosis in the erythropoietic system of rats.