A Novel Nanocombination of Lactoferrin With Green Synthesized Zinc Oxide Nanoparticles for Alleviating Bleomycin‐Induced Oxidative Stress and Cardiotoxicity in Male Rats

This study aimed to use one-step, instantaneous and cost-effective technique for green fabrication of zinc oxide nanoparticles (ZnONPs) by methanolic extract of Coleus forskohlii Briq, and their alleviating potency, in combination with lactoferrin (LF/ZnONPs), against bleomycin (BLM)-induced cardiotoxicity. ZnONPs that were biosynthesized and coated with lactoferrin (LF) from cows were analyzed utilizing various instruments. Biosynthesized ZnONPs were agglomerated with condensed oval to semi-rod shaped with average size of 102.32 ± 6.57 nm and zeta potential of -19.45 ± 0.35 mV. LF/ZnONPs had higher particle size (185.43 ± 7.4 nm) with negatively charged surfaces of -25.65 ± 4.35 mV. BLM-intoxicated group exhibited an increasing of the levels of cardiac MDA, NO, and serum potassium, GM-CSF, IL-1β, TNF-α, TGF-β, LDH, total CK, cholesterol, LDL-c and triglycerides; whereas serum HDL-c, Na⁺ and Ca⁺⁺, cardiac GSH, GPx and Na^+/K⁺-ATPase values were significantly decreased. The treatment with LF/ZnONPs resulted in a significant restore of the mentioned measurements near to those of control group. Histopathological changes in cardiac tissue and immunohistochemistry analysis supported the results obtained from the biochemical analysis reflecting the ability of these supplements in counteracting bleomycin-induced cardiotoxicity. The treatment with LF/ZnONPs was more effective than LF and ZnONPs alone with safe therapeutic efficiency against BLM-induced cardiotoxicity, which attributed to its antioxidative and anti-inflammation properties.