Differential effect of Taraxacum officinale L. (dandelion) root extract on hepatic and testicular tissues of rats exposed to ionizing radiation.

Exposure to high doses of radiation negatively impacts on human organs. Dandelion (Taraxacum officinale ) L. has been used as a traditional folk. This study was to investigate the effect of dandelion root extract (DRE) on radiation -induced hepatic and testicular tissues injury. Animals were exposed to 8.5 Gy of gamma radiation applied as a shot dose and DRE (200 mg/kg/day), was orally supplemented to rats 14 days before and after irradiation. The results showed that DRE administration attenuated oxidative stress in the liver and testis denoted by a significant reduction in the level of MDA and PCO with a marked elevation in GSH and the activity of SOD, CAT and Gpx. Moreover, DRE administration showed positive modulation in the activity of PNPase, GLDH and GSH-Ts. Additionally, these alterations were associated with a significant decrease in the activity of ALT, AST, ALP, and LDH with a marked increase of AL level. Further, elevated levels of testosterone, LH and inhibin B, as well as StAR and P450scc gene expression and Zn level with a decrease of FSH level were noticed. Also, DRE reduced the level of IL-1ß, TNF-α, and caspase-3. Also administration of DRE significance diminished the histopathological changes in the hepatic and testicular tissues, denoted by a reduction in the necrotic and degenerative changes of hepatocytes or fibrinoid necrosis of congested central vein and improving the seminiferous tubules and interstitial tissue between the tubules of the testis. In conclusion, treatment with DRE pre-irradiation is effective on both liver and testicular tissues of rats. Meanwhile, in the case of post-radiation administration, DRE was more effective on testicular tissue than liver. So we suggest that it is better to use the dandelion before exposure to radiation rather than after it.

Effect of Low-Level Laser on Some Metals Related to Redox State and Histological Alterations in the Liver and Kidney of Irradiated Rats.

Low-level laser therapy (LLLT) is a type of medicine that uses laser light at low levels to activate the cellular chromophores and the initiation of cellular signaling. This study aimed to evaluate the photomodulation effect of LLL against ionizing radiation (IR)-induced metal disorders related to redox state in the liver and kidney of male rats. Rats were divided into 4 groups (control, LLLT, IR (7Gy), IR+LLLT). The results showed that LLLT 870 nm one time for 3 days post-irradiation revealed redistribution of iron (Fe), copper (Cu), zinc (Zn),calcium (Ca), magnesium (Mg), manganese (Mn), and selenium (Se) in the liver and kidney tissues. Moreover, LLLT attenuated the oxidative stress manifested by a marked reduction of hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE), total oxidant state (TOS), and oxidative stress index (OSI) associated with a significant increase in total antioxidant status (TAS), glutathione (GSH) content, and glutathione peroxide (GPx), glutathione reductase (GRx), superoxide dismutase(SOD), and catalase (CAT) activities. Moreover, LLLT displayed an increase in glutathione-S-transferase (GSH-T) and ceruloplasmin activities and a decrease in the activity of gamma-glutamyl transferase (γ-GT). Besides, LLLT significantly attenuated the histological changes in the liver and kidney tissues, denoted by a reduction in the necrotic and degenerative changes of hepatocytes and an improvement in the corpuscles and tubules of the kidney. In conclusion, LLLT could be used as an adjuvant treatment post-exposure to radiation, while it is not beneficial to use it on the normal tissue.

Ameliorative effect of kefir against γ-irradiation induced liver injury in male rats: impact on oxidative stress and inflammation.

Ionizing radiation is a double-edged sword because of its benefits and risks to human health. Therefore, protecting human organs from harmful effects of radiation is an important concern of researchers. Kefir, as a good source of probiotics, received growing interest in protective medicine owing to its antioxidant, anti-inflammatory, and immunomodulatory properties. Thus, this study was planned to investigate the protective role of kefir against γ-radiation-induced hepatotoxicity. Thirty-two male rats were distributed in four groups: (I) control, (II) received Kefir orally (5 ml/kg body weight) for 28 days, (III) exposed to whole body γ-irradiation (6.5 Gy) to induce hepatotoxicity, and (IV) was pretreated with kefir for 21 days then exposed to γ-irradiation followed by 7 days of kefir treatment. At the end of the experiment, complete blood picture (CBC), liver function, and lipid profile were estimated. Furthermore, levels of lipid peroxidation, nitric oxide content, and endogenous antioxidants, in addition to concentrations of copper, iron, and calcium were measured in liver tissue. Furthermore, monocyte chemoattractant protein-1 (MCP-1) and relative gene expression of nuclear factor kappa (NF-κB) were assessed. The results revealed that oral administration of kefir significantly reduced the radiation-induced hepatic histological alterations, hepatic function impairment, and dyslipidemia. Moreover, kefir notably ameliorated the state of oxidative stress and appeared to inhibit the induced inflammation. This study provides a possible counteracting role of kefir against hepatotoxicity induced γ-radiation. This can focus the benefit of kefir application as a prophylactic treatment to limit hepatic inflammation during radiotherapy.

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.

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.

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.

Mechanisms involved in the possible nephroprotective effect of rutin and low dose γ irradiation against cisplatin-induced nephropathy in rats.

Cisplatin has demonstrated high antitumor efficacy. However, nephrotoxicity is a dose-limiting factor in its clinical use. The present study was designed to investigate the protective effect of rutin and low dose of irradiation (LDR) on cisplatin-induced nephrotoxicity in rats. Rats received rutin (200mg/kg/day, p.o) for 10 consecutive days and subjected to LDR (0.5Gy) 1day prior to cisplatin. Intraperitoneal administration of single dose of cisplatin (7.5mg/kg) was used to induce nephrotoxicity. Data showed that cisplatin caused elevation in serum creatinine and urea, disturbance in blood count, elevation in gene expression of tumor necrosis factor alpha, nuclear factor kappa B, interleukin-1ß, caspase-3, mitochondrial cytochrome C and apoptosis-inducing factor in renal tissue. Moreover, it caused elevation in renal malondialdehyde accompanied by reduction in glutathione content. These effects were confirmed by histopathological examination. It was observed that LDR and rutin ameliorated the studied parameters. In conclusion, LDR could be considered as a novel approach for prophylaxis of cisplatin induced renal damage, also it augmented the nephroprotective effect of rutin via modulating the expression of inflammatory, oxidative stress and apoptotic mediators as well as histological changes in rats kidneys and hence might be valuable in improving the therapeutic index of cisplatin.

Antioxidant and antiapoptotic effects of sea cucumber and valsartan against doxorubicin-induced cardiotoxicity in rats: The role of low dose gamma irradiation.

Doxorubicin (DOX) is a highly effective antineoplastic drug; however, the clinical use of DOX is limited by its dose dependent cardiotoxicity. This study was conducted to evaluate the cardioprotective effect of sea cucumber and valsartan against DOX-induced cardiotoxicity in rats. Also, the role of exposure to low dose γ radiation (LDR) on each of them was investigated, since LDR could suppress various reactive oxygen species-related diseases. Rats received DOX (2.5mg/kg, ip) in six equal injections over a period of 2weeks, sea cucumber (14.4mg/kg, p.o) and valsartan (30mg/kg, p.o) for 8 successive weeks. Exposure to LDR (0.5Gy) was performed one day prior to DOX. Results revealed that DOX administration elevated serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK-MB) and troponin-I as well as increased cardiac lipid peroxide content and myeloperoxidase (MPO) activity. Additionally, it increased cardiac expressions of iNOS and caspase-3, accompanied by reduction in cardiac total protein and glutathione (GSH) contents. Treatment with sea cucumber or valsartan improved the cardiotoxicity of DOX. Their adjuvant therapy with LDR offers an additional benefit to the cardioprotection of the therapeutic drugs. These results confirmed by histopathological examination. In conclusion, sea cucumber and valsartan alone or combined with LDR attenuated DOX-induced cardiotoxicity via their antioxidant and anti-apoptotic activities and thus might be useful in the treatment of human patients under doxorubicin chemotherapy.

Chemopreventive Activity of MGN-3/Biobran Against Chemical Induction of Glandular Stomach Carcinogenesis in Rats and Its Apoptotic Effect in Gastric Cancer Cells.

In the current study, we investigated the chemopreventive activity of arabinoxylan rice bran, MGN-3/Biobran, against chemical induction of glandular stomach carcinogenesis in rats. Gastric cancer was induced by carcinogen methylnitronitrosoguanidine (MNNG), and rats received MNNG alone or MNNG plus Biobran (40 mg/kg body weight) for a total of 8 months. Averaged results from 2 separate readings showed that exposure to MNNG plus Biobran caused gastric dysplasia and cancer (adenocarcinoma) in 4.5/12 rats (9/24 readings, 37.5%), with 3.5/12 rats (7/24 readings, 29.2%) showing dysplasia and 1/12 rats (8.3%) developing adenocarcinoma. In contrast, in rats treated with MNNG alone, 8/10 (80%) developed dysplasia and adenocarcinoma, with 6/10 rats (60%) showing dysplasia and 2/10 rats (20%) developing adenocarcinoma. The effect of combining both agents was also associated with significant suppression of the expression of the tumor marker Ki-67 and remarkable induction in the apoptotic gastric cancer cells via mitochondrial-dependent pathway as indicated by the upregulation in p53 expression, Bax expression, downregulation in Bcl-2 expression, an increase in Bax/Bcl-2 ratio, and an activation of caspase-3. In addition, Biobran treatment induced cell-cycle arrest in the subG1 phase, where the hypodiploid cell population was markedly increased. Moreover, Biobran treatment protected rats against MNNG-induced significant decrease in lymphocyte levels. We conclude that Biobran provides protection against chemical induction of glandular stomach carcinogenesis in rats and may be useful for the treatment of human patients with gastric cancer.

Hydroferrate fluid, MRN-100, provides protection against chemical-induced gastric and esophageal cancer in Wistar rats.

In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma.

Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body γ-irradiation in mice via restoration of hematopoietic tissues.

The aim of the current study is to examine the protective effect of MGN-3 on overall maintenance of hematopoietic tissue after γ-irradiation. MGN-3 is an arabinoxylan from rice bran that has been shown to be a powerful antioxidant and immune modulator. Swiss albino mice were treated with MGN-3 prior to irradiation and continued to receive MGN-3 for 1 or 4 weeks. Results were compared with mice that received radiation (5 Gy γ rays) only, MGN-3 (40 mg/kg) only and control mice (receiving neither radiation nor MGN-3). At 1 and 4 weeks post-irradiation, different hematological, histopathological and biochemical parameters were examined. Mice exposed to irradiation alone showed significant depression in their complete blood count (CBC) except for neutrophilia. Additionally, histopathological studies showed hypocellularity of their bone marrow, as well as a remarkable decrease in splenic weight/relative size and in number of megakaryocytes. In contrast, pre-treatment with MGN-3 resulted in protection against irradiation-induced damage to the CBC parameters associated with complete bone marrow cellularity, as well as protection of the aforementioned splenic changes. Furthermore, MGN-3 exerted antioxidative activity in whole-body irradiated mice, and provided protection from irradiation-induced loss of body and organ weight. In conclusion, MGN-3 has the potential to protect progenitor cells in the bone marrow, which suggests the possible use of MGN-3/Biobran as an adjuvant treatment to counteract the severe adverse side effects associated with radiation therapy.