Impact of zinc oxide nanoparticles on thioredoxin-interacting protein and asymmetric dimethylarginine as biochemical indicators of cardiovascular disorders in gamma-irradiated rats.

Nanoparticle is a microscopic particle that has been existed in a wide range of biotechnological purposes. Zinc oxide nanoparticles (ZnO-NPs) have fewer environmental hazards and have shown positive impacts in the medical field. This work aimed to observe the effects of low and high doses of ZnO-NPs on heart injury induced by ionizing radiation (IR). Animals were irradiated by 8 Gy of gamma rays and ZnO-NPs (10 and 300 mg/Kg/day) were orally delivered to rats 1 hour after irradiation. Animals were dissected on 15th day postirradiation. Data showed that the oxidative damage resulted from radiation exposure, appeared by marked increments in the malondialdehyde (MDA) content and the level and protein expression of thioredoxin-interacting protein (TXNIP) with a noticeable decline in the level and expression of thioredoxin 1 (Trx-1) and thioredoxin reductase (TrxR), as well as glutathione (GSH) level and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, radiation-induced inflammation, manifested by a noticeable elevation in the level of tumor necrotic factor-alpha (TNF-α), interleukin-18 (IL-18), and C-reactive protein (CRP). Additionally, endothelial dysfunction marked with a high level of asymmetric dimethylarginine (ADMA), total nitrite/nitrate (NOx), intercellular adhesion molecule 1 (ICAM-1), homocysteine (Hcy), creatine kinase (CK-MB), cardiac troponin-I (cTn-I), and lactate dehydrogenase (LDH). In addition, a decrease of zinc (Zn) level in the cardiac tissue was recorded. ZnO-NPs treatment (10 mg/kg) mitigated the oxidative stress and inflammation effects on the cardiovascular tissue through the positive modulations in the studied parameters. In contrast, ZnO-NPs treatment (300 mg/kg) induced cardiovascular toxicity of normal rats and elevated the deleterious effects of radiation. In conclusion, ZnO-NPs at a low dose could mitigate the adverse effects on cardiovascular tissue induced by radiation during its applications, while the high dose showed morbidity and mortality in normal and irradiated rats.

Mitigating effect of biotin against irradiation-induced cerebral cortical and hippocampal damage in the rat brain tissue.

Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors. The brain is oversensitive to oxidant injury induced by radiation. Biotin is a member of the vitamin B complex family and its deficiency has been associated with neurogenesis impairment in animals and humans. The present study was undertaken to investigate the mitigating effect of biotin on the cerebral cortical and hippocampal damage induced by radiation exposure. Animals were exposed to radiation in the presence or absence of biotin and sacrificed on day 10. The results demonstrated that the administration of biotin 2 mg to irradiated rats had no significant effect on the radiation-induced damage of the cerebral cortex and the hippocampus, while the administration of biotin 6 mg has significantly attenuated oxidative stress in the hippocampus, manifested by a reduction of 4-hydroxynonenal (4HNE), total nitrate/nitrite (NOx), and xanthine oxidase (XO) levels associated with an elevation of glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities. In addition, biotin decreased the pro-inflammatory cytokines (interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrotic factor alpha (TNF-α)), caspase-3, poly(ADP-ribose) polymerase 1 (PARP1) level, and PARP1 gene expression. Moreover, biotin 6 mg treatment diminished serum S100 protein (S100B) and neuron-specific enolase (NSE) levels. In conclusion, biotin treatment at high dose post-irradiation has efficiently neutralized the effect of free radicals in the hippocampal region of rats. Thus, it could be applicable as a radio-mitigator for reducing or delayed radiation-induced brain injury in patients post-radiotherapy.

Role of betaine in liver injury induced by the exposure to ionizing radiation.

Oxidative stress, apoptosis, and fibrosis may play a major role in the development of radiation-induced liver damage. Betaine, a native compound widely present in beetroot, was reported to possess hepato-protective properties. The objective of this study was to investigate the influence of betaine on radiation-induced liver damage. Animals were exposed to 9 Gy applied in 3 doses of 3 Gy/wk. Betaine (400 mg/kg/d), was orally supplemented to rats after the first radiation dose, and daily during the irradiation period. Animals were sacrificed 1 day after the last dose of radiation. The results showed that irradiation has induced oxidative stress in the liver denoted by a significant elevation in malondialdehyde, protein carbonyl, and 8-hydroxy-2-deoxyguanosine with a significant reduction in catalase activity and glutathione (GSH) content. The activity of the detoxification enzyme cytochrome P450 (CYP450) increased while GSH transferase (GSH-T) decreased. The activity of the apoptotic marker caspase-3 increased concomitant with increased hyaluronic acid, hydroxyproline, laminin (LN), and collagen IV. These alterations were associated with a significant increase of gamma-glutamyl transferase, alkaline phosphatase and alanine and aspartate aminotransferase markers of liver dysfunction. Betaine treatment has significantly attenuated oxidative stress, decreased the activity of CYP450, enhanced GSH-T, reduced the activity of caspase-3, and the level of fibrotic markers concomitant with a significant improvement of liver function. In conclusion, betaine through its antioxidant activity and by enhancing liver detoxification and reducing apoptosis may alleviate the progression of liver fibrosis and exert a beneficial impact on radiation-induced liver damage.