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 On the 15th day, mice were weighed, blood withdrawn then sacrificed and hearts were removed to estimate various biochemical and histopathological parameters.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.
Keywords: Cardiac inflammation; Cardiotoxicity; Cyclophosphamide; Levocabastine; Oxidative stress.
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