Oxfendazole

Oxfendazole (OX) induces not only mRNA expression of phase I enzymes Cyp1a1, Cyp1a2, but also Nrf2-regulated phase II enzymes such as Gpx2, Nqo1, Yc2, Akr7a3 and Gstm1 in rats, presumably due to an adaptive response against OX-induced oxidative stress. Oxfendazole enhances oxidative DNA damage (as assessed by 8-hydroxydeoxyguanosine; 8-OHdG) and lipid peroxidation (as assessed by thiobarbituric acid-reactive substances; TBARS) in rats. ^[1] Oxfendazole administered at the therapeutic dose (4.5 mg/kg) and at the highest dose (22.5 mg/kg) increase 1.54- and 2.36-fold the total liver microsomal cytochrome P450 and more particularly the isoenzyme P450IA2 (95% and 184% increases) in rabbit liver. ^[2] Oxfendazole MRL induces a mutagenic effect in all tested cell types. Oxfendazole exhibits embryotoxicity including teratogenicity. Oxfendazole induces a disturbance in the different biochemical contents of all tested tissues in mice. ^[3] Oxfendazole increases the incidence and multiplicity of altered foci (4.0- and 3.6-fold, respectively) and hepatocellular adenomas (HCAs) (3.0- and 5.5-fold, respectively). Oxfendazole treatment induces 5.2- and 5.6-fold increases in the number of proliferating cell nuclear antigen (PCNA)-positive cells and single-stranded DNA (ssDNA)-positive cells in HCAs compared with the surrounding tissue, respectively. ^[4] Oxfendazole and its sulphone metabolite attain a significantly higher plasma concentration and remain much longer in plasma compared with fenbendazole (FBZ) and albendazole (ABZ) and their respective metabolites in dogs. ^[5]