The investigation of protective role of acetyl l-carnitine on cisplatin myelosuppression in experimental animal model

Materials and methods: Four groups of twenty-eight adult female Wistar albino rats were taken in this study. The groups were like these: Group 1: Control, group 2:Acetyl L-carnitine (ALCAR), group 3: Cisplatin, group 4: ALCAR+Cisplatin administered groups. Baseline complete blood count and peripheral blood smear of all the rats were obtained for confirming if there was any bone marrow suppression at the beginning of the study. All rats were given 5 ml/kg/dose intraperitoneal normal saline injection once a day for hydration over three days. Yet over three days (-2, -1 and 0. days) group 2 and group 4 were injected with acetyl L-carnitine (200 mg/kg) subcutaneously while group 1 and group 3 were injected with same volumes of normal saline. On the third day (0.day) of study, rats in group 3 and group 4 were given cisplatin 8 mg/kg/dose by intraperitoneal infusion in one hour; rats in group 1 and group 2 were given intraperitoneal infusion of normal saline in equal volume. All rats were sacrificed on the tenth day of cisplatin infusion and their femurs were dissected. Bone marrow samples were painted with Wright stain and all three sequences (myeloid, lymphoid and erythroid cells) were evaluated. Acute cellular changes related to chemotherapy evaluated on Wright stained imprints. Contour and size irregularities in cells, stoplasmic bulges, nuclear vacuolization, disruption on nuclear membrane; all of these were evaluated for severity and the number of effected cells. Sections of parafine blocs prepared with hematoxilen eosin stain were evaluated in light microscope for cellularity, bone marrow cell components, maturation, fibrosis, necrosis, hemorrhage, adipose tissue rate.Results: All baseline complete blood count and peripheral blood smear of rats were normal at the beginning of the study. Bone marrow evaluation of all rat groups were like following: In group 1 (Control) mean cellularity was %93.57±3.7, there was no maturation halt. Bone marrow cells assessed on light microscope, myeloid colony %40.85±3.4 , lymphoid colony %47.42±3.7, erythroid colony %11.71±1.7 in this group. In group 2 (ALCAR) mean cellularity was %95±4, there was no maturation halt. Myeloid colony %43.14±2.5, lymphoid colony %45.42±2.5, erythroid colony %11.42±1.5 in this group. In group 3 (Cisplatin) mean cellularity was %61.66±5.1, there was maturation halt in this group. Myeloid colony %22.33±1.5, lymphoid colony %26.66±3.2, erythroid colony %50.66±4.1 in this group. In group 4 (ALCAR+Cisplatin) mean cellularity was %71,42±4.7 and maturation halt was more mild compared to cisplatin administered group. Myeloid colony %32±1.6, lymphoid colony %36.28±2.6, erythroid colony %31.71±3.3 in group 4. As compared to control and ALCAR groups; cellularity, lymphoid and myeloid cell rates were lower in cisplatin administered group. As compared to control group, there was myelosuppression in ALCAR+cisplatin administered group. As compared to only cisplatin administered group cellularity, lymphoid and myeloid colonies were significantly high.Conclusion : In this study, it was featured that the myelosuppressive effect of cisplatin reduced by using acetyl L-carnitine in experimental myelosuppression model created by cisplatin administring.Key words: Acetyl L-carnitine, cisplatin, myelosuppression