Evaluating the hepatotoxic versus the nephrotoxic role of iron oxide nanoparticles: One step forward into the dose-dependent oxidative effects.

The present study has been designed to detect the dose-dependent effect of iron oxide nanoparticles (IONPs) on the liver and kidney of rats by evaluating three different doses 30, 300, 1000 mg/kg/day IONPs for 28 days. Forty rats were divided into four groups; I (control), II (low dose), III (medium dose) and IV (high dose). There also was a statistically-significant elevation in the serum levels of hepatic enzymes; AST and ALT in medium & high dose. The elevation of serum ALP, on the other hand, was significant in all IONPs doses. There was significant elevation in the levels of urea creatinine, and MDA in the medium and high doses of IONPs. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed significant decrease in the high dose only compared to the control group. The serum iron levels increased in a dose-dependent manner in the IONPs-treated groups with highly significant increase in the moderate and high dose groups. On comparing the effect of different doses of IONPs between the liver and kidney, the high dose revealed statistically significant difference (p < 0.05) in the area percent of collagen deposition (54.4 ± 3.9 versus 6.1 ± 2.6) and alpha smooth muscle actin (α-SMA) reaction (7.7 ± 1.5 versus 17.8 ± 4.3) in the liver relative to the kidney. The medium and high doses revealed statistically significant difference in optical density of Periodic acid Schiff (PAS) reaction (45 ± 3.4 versus 50.3 ± 1.8 in the medium dose, and 38.9 ± 6 versus 63 ± 3 in the high dose) and area percent of inducible nitric oxide synthase (iNOS) reaction (12.98 ± 2.7 versus 3.5 ± 0.5 in the medium dose, and 27.91 ± 1.5 versus 7.7 ± 0.6 in the high dose) in the liver relative to the kidney.