Gerashchenko Bogdan I, Sarnatskaya Veronika V, Bardakhivska Kvitoslava I, Sydorenko Oleksii S, Kolesnik Denis L, Klymchuk Dmytro O
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology (IEPOR), National Academy of Sciences of Ukraine, Vasylkivska Str. 45, Kyiv, 03022, Ukraine.
M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine, Tereshchenkivska Str. 2, Kyiv, 01601, Ukraine.
Heliyon. 2023 Jul 18;9(7):e18414. doi: 10.1016/j.heliyon.2023.e18414. eCollection 2023 Jul.
Chemotherapy can often cause a variety of side effects including bone marrow (BM) suppression, termed as myelosuppression. Accordingly, facile and effective management of chemotherapy-induced myelosuppression is currently a pivotal task for experimental pathologists and oncologists. Here, we chose to use activated carbon (AC) with an extensive surface area for studying its possible protective effectiveness with respect to BM in doxorubicin (DOX)-treated rats. Spherical AC with an extended surface area up to 4490 m/g was prepared for (p/o) delivery, whereas for intraperitoneal (i/p) delivery we used the powdered form of AC that was derived from the aforementioned spherical AC. During the monthly treatment of animals with AC and DOX these two components were delivered alternately (not in the same day). After treatment, BM cells were isolated from femurs of sacrificed animals, stained with acridine orange (AO) and analyzed by flow cytometry. Regardless of the route of AC delivery (p/o or i/p), apparent myeloprotection with a possible regenerative effect was observed in animals that received DOX, as evidenced by recovery of the populations of total nucleated cells (TNC) and polychromatic (immature) erythrocytes accompanied by a considerable reduction of the number of apoptotic/dead cells among TNC (≤2.0%). Moreover, as a result of AC administrations, there was a significant increase of AO green and far-red fluorescence intensities in the population of TNC, which is suggestive of the ongoing quantitative and conformational changes in DNA and RNA associated with cell recovery and proliferation. Thus, AC preparations under the present experimental conditions can effectively tackle DOX-induced myelosuppression via mechanisms not necessarily associated with adsorptive detoxification.
化疗常常会引发多种副作用,包括骨髓抑制,也称为骨髓抑制作用。因此,简便有效地管理化疗引起的骨髓抑制是目前实验病理学家和肿瘤学家的一项关键任务。在此,我们选择使用具有广泛表面积的活性炭(AC),来研究其对阿霉素(DOX)处理的大鼠骨髓可能的保护作用。制备了表面积高达4490 m/g的球形AC用于口服给药,而对于腹腔内给药,我们使用了由上述球形AC衍生而来的粉末状AC。在每月用AC和DOX对动物进行治疗期间,这两种成分交替给药(不在同一天)。治疗后,从处死动物的股骨中分离出骨髓细胞,用吖啶橙(AO)染色并通过流式细胞术进行分析。无论AC的给药途径是口服还是腹腔内给药,在接受DOX的动物中均观察到明显的骨髓保护作用以及可能的再生效应,表现为总核细胞(TNC)和多色(未成熟)红细胞数量的恢复,同时TNC中凋亡/死亡细胞数量显著减少(≤2.0%)。此外,由于给予了AC,TNC群体中AO绿色和远红色荧光强度显著增加,这表明与细胞恢复和增殖相关的DNA和RNA正在发生定量和构象变化。因此,在当前实验条件下,AC制剂可通过不一定与吸附解毒相关的机制有效应对DOX诱导的骨髓抑制。