Radioprotective Effect of Zinc Nanoparticles on Ionizing Radiation-induced Nephrotoxicity in Mice.

INTRODUCTION: Ionizing radiation (IR) causes oxidative stress in kidneys and subsequently disrupts renal function. The use of green synthesized zinc nanoparticles (Zn NPs) with antioxidant properties may reduce the damage caused by IR. METHODS: Thirty-six mice were kept in a standard situation and divided into 6 groups: 1: Control; 2-4: receiving 5 mg/kg, 10 mg/kg, and 25 mg/kg of Zn NPs with IR; 5: receiving 5 mg/kg of ZnSO4 with IR; and 6: IR. After 15 days, half of the animals in each group were sacrificed and their blood samples isolated to evaluate the plasma urea and creatinine levels. The kidneys were kept for evaluating the glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels; on 21st day, the rest of the animals were sacrificed and their kidneys removed for histological assessments. RESULTS: IR decreased GSH content, increased MDA level, and reduced SOD and CAT activity. On the other hand, Zn NPs at 10 and 25 mg/kg doses increased GSH, decreased MDA, and enhanced SOD and CAT activities. Zn NPs treatment at 10 and 25 mg/kg doses decreased the plasma urea and creatinine levels induced by IR. Moreover, Zn NPs significantly decreased the level of urea and creatinine in irradiated mice in comparison with IR alone (p < 0.05). The main histopathological results were tubular and glomerular atrophy and interstitial fibrosis in irradiated mice, while tubular degeneration and atrophy were less frequent in Zn NPs + IR group than in IR group alone. CONCLUSION: Zn NPs treatment, especially at 25 mg/kg dose, attenuates the side effect of IR on kidneys through reducing oxidative stress factors, biochemical, and histopathological changes.

Ondansetron enhanced diclofenac-induced nephrotoxicity in mice.

This study was performed to investigate the effect of ondansetron, a serotonin receptor (5-HT3) antagonist, in the alleviation of diclofenac-induced kidney injuries. NMRI mice were randomly divided into six groups and treated with (A) untreated control group, (B) diclofenac (100 mg/kg), (C) ondansetron (1 mg/kg), (D to F) ondansetron (0.1, 0.5, and 1 mg/kg, respectively) and diclofenac (100 mg/kg) for last 3 days of experiment. The oxidative stress tests strongly demonstrated the negative synergistic effects of diclofenac and ondansetron, regarding the observation of dose-dependent enhancement of malondialdehyde concentration, and reduction of glutathione content, and superoxide dismutase and catalase activity. Histopathological analyses revealed dose-dependent tubular epithelial cells degeneration, outstanding mononuclear cells infiltration, clear necrosis at the papillary region of kidney, dilation, and vascular hyperemia in mice kidney tissues treated with ondansetron and diclofenac. Conclusively, these findings suggested the possible ondansetron-diclofenac interaction through the induction of oxidative stress.

Toxicity of microwave-assisted biosynthesized zinc nanoparticles in mice: a preliminary study.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD50) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30-80 nm. The LD50 value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.