Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

Abstract

Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX). However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine), a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p.) significantly inhibited the generation of reactive oxygen species (ROS) and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG), and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h). Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity.

Protective Effect of Bergenin against Cyclophosphamide-Induced Immunosuppression by Immunomodulatory Effect and Antioxidation in Balb/c Mice

“…The oxidative DNA damage in cells is the main side effect of chemotherapy drugs including cyclophosphamide [ 6 ]. The modulation of oxidative stress and inflammatory cytokine production through stimulation of immunity may help in maintaining a disease-free state [ 35 ].…”

“…Generally, chemotherapeutics drugs often generate many harmful side effects such as cytotoxic effects and host immunosuppression, no matter how great of their therapeutic effects are [ 4 ]. Cyclophosphamide (Cy), an alkylating agent, has been widely used as chemotherapeutic drug which results in a lot of adverse effects including immunosuppression, bone marrow suppression, leucopenia and oxidative stress [ 5 , 6 , 7 , 8 ]. It has been reported that Cy can generate oxidative stresses, mediate disruption of the redox balance, and lead to biochemical and physiological disturbances [ 9 ].…”

Immunomodulatory Effect of Tremella Polysaccharides against Cyclophosphamide-Induced Immunosuppression in Mice

“…Cyclophosphamide (CY), an alkylating agent, has been most widely used to treat autoimmune diseases and cancer [ 14 , 15 ]. CY is also a cytotoxic drug, but it has no activity in vitro, and it can damage the structure of DNA, cut off its copy that can lead to cell death in vivo [ 16 , 17 ]. Research showed that the long-term use of CY had harmful side effects, such as immunosuppression, myelosuppression and leucopenia [ 18 ].…”

Regulation on BCAAs catabolism pathway plays the key role in cyclophosphamide-induced leucopenia BALB/c mice after the treatment of a typical Traditional Chinese Medicine of Lvjiao Buxue Granules

“…The liver is the main drug metabolism organ in mammals. Metabolized cyclophosphamide causes damage to mitochondria and damage to cellular respiration, which affects the onset of lipid peroxidation and an increase in reactive oxygen species [33,34]. In this work, signi cant increases in Liver index were observed through the impact of cyclophosphamide, and this altered were regulated by Lvjiao Buxue Granules' treatment.…”