Cerium oxide nanoparticles display antioxidant and antiapoptotic effects on gamma irradiation-induced hepatotoxicity.

Throughout radiotherapy, radiation of the hepatic tissue leads to damage of the hepatocytes. We designed the current study to examine how cerium oxide nanoparticles (CONPs) modulate gamma irradiation-induced hepatotoxicity in rats. Animals received CONPs (15 mg/kg body weight [BW], ip) single daily dose for 14 days, and they were exposed on the seventh day to a single dose of gamma radiation (6 Gy). Results showed that irradiation increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities. Furthermore, it elevated oxidative stress biomarker; malondialdehyde (MDA) and inhibited the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in hepatic tissues homogenate. Additionally, hepatic apoptotic markers; caspase-3 (Casp-3) and Casp-9 were elevated and the B-cell lymphoma-2 (Bcl-2) gene level was decreased in rats exposed to radiation dose. We observed that CONPs can modulate these changes, where CONPs reduced liver enzyme activities, MDA, and apoptotic markers levels, in addition, it elevated antioxidant enzyme activities and Bcl-2 gene levels, as well as improved histopathological changes in the irradiated animals. So our results concluded that CONPs had the ability to act as radioprotector defense against hepatotoxicity resulted during radiotherapy.

Gallic acid and/or cerium oxide nanoparticles synthesized by gamma-irradiation protect cisplatin-induced nephrotoxicity via modulating oxidative stress, inflammation and apoptosis.

Cisplatin is one of the most significant anticancer. However, its use is associated with numerous toxicities especially nephrotoxicity. The main aim of this work was to examine the protective effect of Gallic acid (GA) and/or cerium oxide nanoparticles (CONPs) synthesized by gamma-irradiation on cisplatin-induced nephrotoxicity in rats. To do that, 48 adult male albino rats were separated into eight groups and received GA (100 mg/kg orally) and/or CONPs (15 mg/kg i. p.) for 10 days before injection with a single dose of cisplatin (7.5 mg/kg i. p.). The findings showed that cisplatin treatment impaired kidney functioning as shown by elevated serum levels of urea and creatinine. Additionally, the oxidative stress indicators (MDA and NO), levels of NF-kB, pro-inflammatory cytokines (IL1-and TNF-) and pro-apoptotic proteins (BAX and caspase-3) were raised after cisplatin injection, while levels of intrinsic anti-oxidants (CAT, SOD, and GSH) and anti-apoptotic protein (Bcl-2) were reduced. Moreover, renal toxicity was confirmed by alteration in normal histological architecture of the kidneys. On the other hand, pretreatment with CONPs and/or GA ameliorated cisplatin-induced nephrotoxicity as evidenced by improvement of renal function parameters and levels of oxidative stress, inflammatory and apoptotic markers in renal tissue along with the renal histopathological changes. This study clarifies how GA and CONPs protect against cisplatin-induced nephrotoxicity and demonstrates any potential synergism between them. Therefore, they can be considered as promising nephroprotective agents during chemotherapy.

Ameliorative effect of selenium nanoparticles and fish oil on cisplatin and gamma irradiation-induced nephrotoxicity in male albino rats.

Cisplatin (CP) is a major antineoplastic drug for the treatment of solid tumors, however, its clinical utility is limited by nephrotoxicity. Also, radiotherapy is an important treatment modality for many malignancies. The present studies were performed to test whether fish oil (FO) and/or selenium nanoparticles (SeNPs) administration have an ameliorative effect on CP and γ-irradiation induced nephrotoxicity. FO and/or SeNPs were administered to male albino rats daily for 12 days before being intraperitoneally injected with a single dose of CP (10 mg/kg body weight) and whole body exposed to a single dose of γ-radiation (0.7 Gy). Biochemical analysis and histopathological examination were performed. Pretreatment with FO and/or SeNPs before the administration of CP and exposure to γ-radiation significantly reduced CP- and γ-radiation-induced high levels of serum urea and creatinine and renal tumor necrosis factor-α, caspase-3 and cyclooxygenase-2, also they significantly prevented renal total antioxidant capacity levels decrease and ameliorated the levels of most studied trace elements. The histopathological results supported the biochemical findings of this study. The administration of FO and/or SeNPs might be useful for preventing nephrotoxicity which can be caused by CP and radiotherapy during the treatment of various malignancies.

Role of Vitamin D on glycemic control and oxidative stress in type 2 diabetes mellitus.

BACKGROUND: Vitamin D deficiency may play a key role in the development of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Several studies have shown that Vitamin D has an antioxidant property. We aimed to investigate 25-hydroxy Vitamin D (25[OH]D) levels in patients with T2DM and in nondiabetic healthy controls and to ascertain the impact of 25(OH)D levels on glycemic control and oxidative stress in T2DM patients. MATERIALS AND METHODS: Thirty male patients with T2DM and twenty age- and socioeconomic status-matched male healthy controls were included in the study. Fasting and postprandial blood sugar and glycated hemoglobin (HbA1c) were measured. Enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) was determined by spectrophotometric assay, and serum levels of 25(OH)D were measured using radioimmunoassay. RESULTS: Serum Vitamin D levels were significantly lower in patients with T2DM than healthy controls (P = 0.015). There was a significantly lower GPx activity in patients with T2DM than controls (P = 0.048), but the difference in SOD activity did not reach statistical significance. There was a significant negative correlation between serum Vitamin D levels and HbA1c (P = 0.016), but no statistical correlation was shown between serum Vitamin D levels and GPx and SOD. CONCLUSION: We conclude that low level of Vitamin D might play a significant role in T2DM pathogenesis. Hence, Vitamin D supplementation may improve glycemic control and oxidative stress in T2DM.

Treatment of hepatotoxicity induced by γ-radiation using platelet-rich plasma and/or low molecular weight chitosan in experimental rats.

Background and aim: Platelet-rich plasma (PRP) is rich in growth factors and plays an important role in tissue healing and cytoprotection. Also, it has been proved that low molecular weight chitosan (LMC) possesses many outstanding health benefits. The aim of this study was to assess the possibility of using PRP and/or fungal LMC to treat hepatotoxicity induced by γ-radiation in albino rats.Materials and methods: Forty-eight adult male albino rats were randomly divided into eight groups. Group I (control), Group II (PRP alone), Group III (LMC alone), Group IV (PRP + LMC), Group V (γ-irradiated alone), Group VI (γ-irradiated + PRP), Group VII (γ-irradiated + LMC), and Group VIII (γ-irradiated + PRP + LMC). The irradiated rats were whole body exposed to γ-radiation (8 Gy) as fractionated doses (2 Gy) twice a week for 2 consecutive weeks. The treated groups received PRP (0.5 mL/kg body weight, s.c.) and/or LMC (10 mg/kg body weight, s.c.) 2 days a week 1 h after every dose of γ-radiation and continued for another week after the last dose of radiation. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities, as well as reduced glutathione (GSH) content, malondialdehyde (MDA), total antioxidant capacity (TAC), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels in the liver tissue and relative expression of microRNA-21 (miR-21) in serum were measured, in addition to histopathological examination.Results: Exposure of rats to γ-radiation resulted in a significant increase in serum ALT and AST activities, hepatic MDA levels, and serum miR-21 relative expression, along with a significant decrease in hepatic GSH content, TAC, and Nrf2 levels. Treatment with PRP and/or fungal LMC after exposure to γ-radiation ameliorated these parameters and improved the histopathological changes induced by γ-radiation.Conclusions: The results demonstrated that PRP and/or LMC inhibited γ-radiation-induced hepatotoxicity and using both of them together seems more effective. They can be a candidate to be studied toward the development of a therapeutic strategy for liver diseases.

Platelet-rich plasma ameliorates gamma radiation-induced nephrotoxicity via modulating oxidative stress and apoptosis.

AIMS: As a source of growth factors and with its cytoprotective properties, platelet-rich plasma (PRP) received considerable attention in regenerative medicine. Thus, this study was designed to evaluate the protective efficacy of PRP against γ-radiation-induced nephrotoxicity. MAIN METHODS: Forty male rats were distributed in four groups: 1) control, 2) PRP, 3) Radiation, and 4) PRP + radiation. Nephrotoxicity was examined in rats after a whole body γ-irradiation at a single dose of 8 Gy. Activated PRP (0.5 ml/kg BW) was injected subcutaneously twice weekly for three successive weeks prior to γ-irradiation. At the end of the experiment, creatinine, urea, albumin, and neutrophil gelatinase-associated lipocalin (NGAL) serum levels, as well as renal relative gene expression level of kidney injury molecule-1 (KIM-1) were estimated. Further, malondialdehyde level, nitric oxide content and reduced glutathione content in addition to superoxide dismutase and catalase activities were measured. Moreover, the expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 proteins were assayed. KEY FINDINGS: PRP pre-treatment significantly reduced the radiation-induced abnormalities in kidney histology and attenuated the induced cell injury. Furthermore, PRP notably ameliorated the state of oxidative stress and appeared to inhibit the induced apoptosis. SIGNIFICANCE: This study lends a probable protective role of PRP against γ-radiation-induced nephrotoxicity which can highlight the possibilities of its application as a complementary procedure during radiotherapy.

Platelet-rich plasma as a potential therapeutic approach against lead nitrate- and/or gamma radiation-induced hepatotoxicity.

Because of the potential regenerative and cytoprotective effects of its content of numerous bioactive growth factors and cytokines, platelet-rich plasma (PRP) became an attractive biomaterial for therapeutic purposes. Therefore, the current study was designed to investigate the potential therapeutic effect of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity. To do so, hepatotoxicity was induced in rats by intraperitoneal administration of lead nitrate (7.5 mg/kg) thrice weekly for two consecutive weeks and/or a whole-body γ-irradiation at a single dose of 6 Gy. Activated PRP (0.5 ml/kg) was injected subcutaneously 24 h after the last dose of lead nitrate and/or γ-irradiation and continued twice weekly for three successive weeks. Lead nitrate intoxication and/or γ-irradiation resulted in a significant elevation of serum alanine transaminase and aspartate transaminase activities accompanied with a significant decrease in serum levels of total protein and albumin. Further, a significant increase in malondialdehyde level and nitric oxide content accompanied with a significant decrease in the reduced glutathione content and the enzyme activities of glutathione-S-transferase, superoxide dismutase, and catalase were observed. Additionally, hepatic extracellular signal-regulated kinase (ERK) and Akt signaling pathways were stimulated. PRP treatment notably ameliorated the induced cell injury, reduced the intracellular oxidative and interestingly increased the upregulation of phosphorylated ERK1/2 and Akt. Moreover, PRP treatment relieved lead nitrate and/or γ-radiation-induced hepatic histological damages. In conclusion, this study sheds the light on a probable therapeutic role of PRP against lead nitrate- and/or γ-radiation-induced hepatotoxicity which might attribute to its ability to activate ERK and Akt signaling pathways.

Correction to: Platelet-rich plasma as a potential therapeutic approach against lead nitrate- and/or gamma radiation-induced hepatotoxicity.

The original publication of this paper contains adjustment errors.