The liver is the most significant organ for the detoxification of toxic substances in the human body. As a biological barrier, it can remove different exogenous substances through phagocytosis. 1 Druginduced liver injury is an extended term that refers to any hepatic injury which results from a prescribed medication. 2 LA is an antineoplastic agent, which is utilized as a therapy for acute lymphoblastic leukaemia (ALL). Asparagine is an essential amino acid for leukaemia cells' growth, but they lack asparagine synthase and rely upon the host's asparagine supply for protein production. LA act as an anti-ALL by catalysing Asparagine degradation into aspartate and ammonia and decreasing the glutamine pool. 3 Amino acid reduction results in depletion in protein synthesis, causing mitochondrial dysfunction, metabolic stress and ROS generation in leukaemia cells, mediating their death. However, this reduced protein synthesis leads to impaired mitochondria β-oxidation and unoxidized fatty acid accumulation in the hepatic parenchyma. This can lead to hepatocyte necrosis, which is not very notable, though steatosis is usually seen in 50%-90% of occasions. 4 Mild elevation of transaminases and

Background Recent advances in the synthesis of bioactive nanoparticles resulted in the discovery and introduction of new bioactive nanoparticles to the pharmaceutical industry. In this regard, this research is aimed to synthesize the zinc oxide nanoparticles (ZnO-NPs) using Hyssopus officinalis L. extract and to evaluate the safety of nanoparticles using Balb/C mice. Methods Forty male mice were divided into four groups and received 0, 50, 100, and 200 mg/kg of ZnO-NPs for thirty days. At the end of the experiment, blood sugar, creatinine, aspartate aminotransferase (A.S.T.), and alanine aminotransferase (A.L.T.) were determined. Furthermore, histopathological and oxidative stress biomarker analyses in liver and kidney tissues were performed. The changes in the major inflammatory- and antioxidant-related genes were determined. Results The results showed that blood sugar and creatinine reduced significantly (P < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. The serum ALT and AST and lipid peroxidation in the liver and kidney tissues were increased significantly (p < 0.05) when 50, 100, and 200 mg/kg ZnO-NPs were supplemented to the diet. Supplementation of ZnO-NPs suppressed the expression of antioxidant-related genes (SOD and CAT) and up-regulated the inflammatory biomarkers (iNOS and TNF- α). The concentration of 200 mg/Kg nanoparticles indicated cellular degeneration and necrosis in the liver and kidney tissues. Conclusions Overall, it can be concluded that supplementation of ZnO-NPs synthesized using Hyssopus Officinalis L. extract in this study at 50 mg/kg or higher concentrations might be toxic to the mice.