环磷酰胺(CP),虽然是一种有效的抗癌药物,导致心脏毒性作为限制其使用的副作用。因此,非常需要一种可以降低心脏毒性并在癌症治疗中用作佐剂的特定药物。在这种情况下,我们旨在评估左卡巴斯汀(LEV)对CP诱导的瑞士白化病小鼠心脏毒性的保护作用.给小鼠施用LEV(50和100μg/kg,i.p.)每天持续14天,CP为200mg/kg,第7天腹膜内一次。在第15天,老鼠称重,抽取血液,然后处死,取出心脏以评估各种生化和组织病理学参数。CP200mg/kg显著增加心肌肌钙蛋白T,LDH,CK-MB,白细胞介素-1β,IL-6,TNF-α,TBARS,亚硝酸盐,减少CAT,GSH,和SOD水平,因此,表现为心脏损伤,炎症,氧化应激,和无足轻重的压力,累积引起心脏毒性。CP还提高了各种标志物的表达,包括裂解的caspase-3,NF-κB,TLR4,NLRP3和心脏组织中的纤维化病变,而血液学参数降低(红细胞,血小板,和Hb)以确认心脏毒性。LEV和非诺贝特(FF)治疗将这些变化逆转为正常,并显示出对CP的显着保护作用。结果显示LEV在恢复CP诱导的心脏毒性方面的保护作用。凋亡,氧化应激,心脏损伤和组织病理学损害。因此,左卡巴斯汀可用作环磷酰胺治疗癌症的佐剂,但需要进一步对各种动物癌症模型进行深入研究才能确定这一事实。
Cyclophosphamide (CP), although a potent anti-cancer drug, causes cardiotoxicity as a side effect that limits its use. Hence, a specific medicine that can lower cardiotoxicity and be utilised as an adjuvant in cancer treatment is very much needed. In this light, we intended to assess the protective potential of levocabastine (LEV) on CP-induced cardiotoxicity in Swiss albino mice. Mice were administered LEV (50 and 100 μg/kg, i.p.) daily for 14 days and CP at 200 mg/kg, intraperitoneally once on the 7th day. On the 15th day, mice were weighed, blood withdrawn then sacrificed and hearts were removed to estimate various biochemical and histopathological parameters. CP 200 mg/kg significantly increased cardiac troponin T, LDH, CK-MB, interleukin-1β, IL-6, TNF-α, TBARS, nitrite, and decreased CAT, GSH, and SOD levels, thus, manifested cardiac damage, inflammation, oxidative stress, and nitrative stress, cumulatively causing cardiotoxicity. CP also elevated the expression of various markers including cleaved caspase-3, NF-κB, TLR4, NLRP3, and fibrotic lesions in cardiac tissues, whereas decreased hematological parameters (RBCs, platelets, and Hb) to confirm cardiotoxicity. LEV and fenofibrate (FF) treatment reversed these changes towards normal and showed a significant protective effect against CP. The results showed the protective role of LEV in restoring CP-induced cardiotoxicity in terms of inflammation, apoptosis, oxidative stress, cardiac injury and histopathological damage. Thus, levocabastine can be used as an adjuvant to cyclophosphamide in cancer treatment but a thorough study with various animal cancer models is further needed to establish the fact.