Γ-irradiated Rats Research Articles

Iron overload induced submandibular glands toxicity in gamma irradiated rats with possible mitigation by hesperidin and rutin.

Radiation triggers salivary gland damage and excess iron accumulates in tissues induces cell injury. Flavonoids are found in some fruits and are utilized as potent antioxidants and radioprotective agents. This study aimed to evaluate the antioxidant and anti-inflammatory effects of hesperidin and rutin on gamma radiation and iron overload induced submandibular gland (SMG) damage and to evaluate their possible impact on mitigating the alteration in mTOR signaling pathway and angiogenesis. Forty-eight adult male Wistar albino rats were randomly assigned to six groups: group C received a standard diet and distilled water; group H received hesperidin at a dose of 100mg/kg; four times a week for four weeks; group U received rutin at a dose of 50mg/kg; three times a week for three weeks; group RF received a single dose (5Gy) of gamma radiation followed by iron at a dose of 100mg/kg; five times a week for four weeks; group RFH received radiation and iron as group RF and hesperidin as group H; group RFU received radiation and iron as group RF and rutin as group U. SMG specimens from all groups were removed at the end of the experiment; and some were used for biochemical analysis, while others were fixed for histological and immunohistochemical examination. In the RF group, several genes related to antioxidants (Nrf-2 and SOD) and DNA damage (BRCA1) were significantly downregulated, while several genes related to inflammation and angiogenesis (TNFα, IL-1β and VEGF) and the mTOR signaling pathway (PIK3ca, AKT and mTOR) were significantly upregulated. Acinar cytoplasmic vacuolation, nuclear pyknosis, and interacinar hemorrhage with distinct interacinar spaces were observed as histopathological changes in SMGs. The duct system suffered significant damage, eventually degenerating entirely as the cells were shed into the lumina. VEGF and NF-κB were also significantly overexpressed. Hesperidin and rutin cotreatment generated partial recovery as indicated by significant upregulation of Nrf-2, SOD and BRCA1 and considerable downregulation of TNF-α, IL-1β, VEGF, PIK3ca, AKT, and mTOR. Although some acini and ducts continued to deteriorate, most of them had a normal appearance. There was a notable decrease in the expression of VEGF and NF-κB. In γ-irradiated rats with iron overload, the administration of hesperidin and rutin may mitigate salivary gland damage.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats

BackgroundMelissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation.MethodsHyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-β1) were determined.ResultsMO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes’ activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-β1/Smad pathway.ConclusionAccordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

The probable radioprotective role of Acacia nilotica L. against biochemical and cytogenetic disorders induced in gamma irradiated male rats

Gum Arabic (Acacia nilotica L.) is a respected plant that has many nutrients and curative practices. It hinders, improves, or manages many disorders. The radio-protective activity of Acacia nilotica was investigated against γ-rays-induced testicle damage in rats. Twenty-four rats were correspondingly distributed into 4 groups; control, Acacia nilotica (15mg/kg, daily for 30 days), γ-irradiated (5Gy γ-rays, single dose) and Acacia nilotica plus γ-rays treated groups. The plasma testosterone and total antioxidant status (TAS) were estimated. Lipid peroxidation; malondialdehyde (MDA), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), also glutathione peroxidase (GPx), catalase (CAT), tumor necrosis factor-α (TNF-α) with interleukin-1β (IL-1β), were determined in the testicle tissues. A testis weight, sperm count and motility, peripheral-blood and bone-marrow micronuclei (PMN and BMN), and frequency of chromosomal aberrations (CAs) were scored. A significant decline in the levels of plasma testosterone with TAS observed in the γ-irradiated rats. The results also showed significantly increased levels of testicle MDA, inflammatory markers, PMN, BMN and CAs frequencies and decrease in testes weight, sperm count and motility and levels of testicle antioxidants markers in gamma irradiated group. All these biochemical and fertility indices results were significantly enhanced in the Acacia nilotica plus γ-rays treated groups. However, the possible alleviate activity of Acacia nilotica on γ-rays-induced testicle injury in rats has not previously conversed, and this is the topic of this study.

β-Sitosterol mitigates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced hepatic injury in γ-irradiated rats.

Liver damage in rats was induced by TAA (150 mg/kg I.P twice a week/3 weeks) and γ-irradiation (single dose 3.5 Gy) and treated with βS (20 mg/kg daily for 30 days). Serum aminotransferase activity, lipid profile and lipid metabolic factors were measured beside liver oxidative stress and inflammatory markers. Moreover, the hepatic expression of ER stress markers (inositol-requiring enzyme 1 alpha (IRE1α), X-box-binding protein 1 (XBP1) and CCAAT/enhancer binding protein homologous protein (CHOP) and apoptotic markers were detected together with histopathological examination. βS diminished the aminotransferase activity, the oxidative stress markers as well as the inflammatory mediators. Furthermore, βS lowered the circulating TG and TC and the hepatic lipotoxicity via the suppression of lipogenesis (Srebp-1c) and improved the β-oxidation (Pparα and Cpt1a) together with the mitochondrial biogenesis (Pgc-1 α). Moreover, the upregulated levels of ER stress markers were reduced upon treatment with βS, which consequently attenuated hepatic apoptosis. βS relieves hepatic injury, ameliorates mitochondrial biogenesis, and reduces lipotoxicity and apoptosis via inhibition of CHOP and ER stress response.

Trans-resveratrol alleviates hepatic and renal injury in γ-irradiated rats.

Although ionizing radiation (IR) has been of immense value to human life due to its involvement in several fields, it doesn't eliminate that exposure to IR results in an array of biological consequences, including oxidative stress, inflammation, and death. Thus, this study aimed to explore the curative effect of trans-Resveratrol (t-Res) on hepatic and renal injury in a rat model exposed to single and fractionated doses of γ-rays. Rats exposed to a single dose of IR (6Gy, as an acute effect) or a fractionated dose of IR (2Gy/time/3days, day after day; to imitate a chronic impact) were treated with t-Res. Then, the radio-protective effect of t-Res was investigated via biochemical and histological estimations in the liver and kidney of rats in the different groups. The data displayed a significant amelioration in biochemical and histological indices in the liver and kidney of rats exposed to IR doses and treated with t-Res. Particularly, t-Res reduced the oxidative stress milieu through decreasing HIF-1α, ROS, and MDA levels associated with increased CAT activity and Nrf-2 gene expression. Also, t-Res improved the inflammatory status via a decrease in TNF-α, NF-κB, SOCS-3, and HSP-70 genes expression linked with elevations in SIRT-1 and P53 genes expression. It could be concluded that t-Res had hepatoprotective and renoprotective effects against the deleterious consequences of γ-rays exposure due to its antioxidant and anti-inflammatory properties.

Evaluation of the radio-protective role of PEG-Fe3O4 NPs on γ-irradiated male Wistar rats

This study explores the conceivable ameliorative outcome of iron oxide nanoparticles (1.5 mg/kg intraperitoneal (IP) injection) on γ-irradiated male Wistar rats. Iron oxide nanoparticles (Fe3O4 NPs) were prepared via the co-precipitation method using polyethylene glycol (PEG) as an emulsifier to yield PEG-Fe3O4 NPs. XRD, TEM, and FTIR clarified that PEG-Fe3O4 NPs were formed with a spherical shape (5–15 nm) and cubic crystal configuration. Whole-body γ-irradiation of rats at 5.5 Gy (single sublethal dose) instigated significant biochemical disorders in the blood picture, protein fractions, lipid profile, liver enzymes, and kidney function after three weeks post-irradiation. Histo-pathological images displayed diverse distortion in the liver and renal architecture after three weeks post-γ-irradiation. These distortions varied from swelling, vacuolization to necrosis and complete degeneration of the epithelial cells. Histopathological image of liver sections of the group injected by PEG-Fe3O4 NPs pre-γ-irradiation (group 4) showed Kupffer cells activation. Likewise, photomicrograph of the same group signposts the inhibition in the kidney morphological alterations induced by γ-irradiation. So In vivo administration of PEG-Fe3O4 NPs pre-γ-irradiation diminishes the impact of γ-irradiation to a great extent on biochemical and histological disorders. On the other hand, administration of the PEG-Fe3O4 NPs post-irradiation couldn't overcome the damaging effect of γ-irradiation. Therefore, PEG-Fe3O4 NPs can be a useful radio-protective agent when administered before γ-irradiation. This study introduces a thorough report on the radio-protective role of PEG-Fe3O4 NPs on γ-irradiated rats exploiting the biosafety of PEG-Fe3O4 NPs.

Effects of Sargassum virgatum extracts on the testicular measurements, genomic DNA and antioxidant enzymes in irradiated rats

Background Oxidative stress and reactive oxygen species (ROS) are primarily responsible for the development of male infertility after exposure to γ-irradiation. The present work aimed to assess the ameliorative and therapeutic roles of the aqueous and ethanolic extracts of the edible seaweed Sargassum virgatum (S. virgatum) on spermatogenesis and infertility in γ-irradiated Wistar rats. Materials and methods Induction of infertility was performed by exposing the rats to 137Cs-gamma rays, using a single dose of 3.5 Gy. γ-irradiated rats were given the S. virgatum ethanolic (S. virgatum-EtOH) and aqueous extracts intraperitoneally on a daily base for two consecutive weeks at doses of 100 and 400 mg/kg body weight (b.wt.) for each seaweed extract. Morphometric data of the testes, semen quality indices, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx), and deoxyribonucleic acid (DNA) fragmentation were assessed. The results obtained were taken during two-time intervals of 15 and 60 days from the commencement of the algal treatments. In vitro antioxidant assays and polyphenolic compounds of S. virgatum were characterized. Results Significant negative changes in the semen quality and morphometric data of the testes, as well as remarkable DNA fragmentation, were detected in the irradiated rats compared to the control. The levels of the endogenous antioxidant enzymes (SOD, CAT, GSH, and GPx) were also significantly diminished. Nonetheless, treatments of γ-irradiated rats with the S. virgatum-EtOH and aqueous extracts significantly improved the above-mentioned enzymes, in addition to noteworthy amendments in the dimensions of the testes, the semen quality, as well as the DNA structure. Conclusions The ameliorative potency of S. virgatum to cure γ-irradiation-induced male infertility, particularly 400 mg/kg ethanolic extract for 60 days, is the result of the consistent therapeutic interventions of its potent antioxidant and anti-apoptotic polyphenols, particularly protocatechuic, p-hydroxybenzoic, rosmarinic, chlorogenic, cinnamic and gentisic acids, as well as the flavonoids catechin, hesperidin, rutin and quercetin. Besides its high-value nutraceutical importance, S. virgatum could be a natural candidate for developing well-accepted radioprotectant products capable of treating γ-irradiation-induced male infertility.

The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling

Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage.

The role of Garcinol in abrogating cyclophosphamide/radiation nephrotoxicity via suppressing Mincle/Syk/NF-κB signaling pathway

Radiation and chemotherapy are toxic agents; their clinical utility, nevertheless, and curative effect are restricted by toxic side consequences such as nephrotoxicity. This study aims to determine the potential protective effects of Garcinol (G) (10 mg/kg/orally/daily for 4 weeks), a natural polyisoprenylated benzophenone, against renal injury in cyclophosphamide (CA) (150 mg/kg i.p. single-dose) and/or radiation (R) delivered as fractionated doses of 2 Gy/week up to total cumulative dose of 6 Gy to induce toxicity in rats. Kidney injury has been examined by histopathological investigation. Garcinol treatment showed amelioration by a significant decrease in the inflammatory markers (IL-1β and IL-6). Similarly, Garcinol-injected rats exhibited a significant decline in monocyte chemotactic protein-1(MCP-1), macrophage inducible c type lectin (Mincle), spleen tyrosine kinase (Syk), transcriptional factor (NF-kB), and toll-like receptor (TLR-4) compared to the CA + R group. Additionally, histopathological and immunohistochemical examination showed that the administration of CA and/or γ-irradiated rats induced severe injury in kidney, and a decrease in Cyclin d1 immunostain level compared to the control group. Finally, this work may verify the protective role of Garcinol significantly shielding the kidney from damage by inhibiting Mincle expression, which also promotes M1 to M2, and prevents Syk and TLR-4/NF-kB activation.

Effect of Spirulina platensis against Thyroid Disorders Associated with Liver Dysfunction and Dyslipidaemia in Irradiated Rats

SPIRULINA platensis (SP) is a nutritional supplement that has a variety of pharmacological properties and it is considered one of the good nutritional supplements for human and animal feed worldwide. Also, exposure to different forms of radiations is almost unavoidable in daily life, especially during radiotherapy. This study aims at evaluating the effect of SP against thyroid dysfunction associated with alteration in liver functions and lipid profile in gamma-irradiated male albino rats. Male rats were divided into four groups 1-Control, 2-Spirulina, rats were given SP via gavages 300mg/kg/day for 15days, 3-Radiation, whole body γ-irradiated rats at a dose of 5Gy, 4-Spirulina+ Radiation, rats were given SP for 15days before irradiation at a dose of 5Gy. The thyroid tissues of the irradiated rats revealed a significant decrease in the activity of the antioxidant enzymes, accompanied by a significant increase in the level of lipid peroxidation end-product malondialdehyde (MDA) indicating radiation-induced oxidative stress. Furthermore, the activity of the apoptotic marker caspase-3 was significantly increased. Also, serum level of thyroid hormones, triiodothyronine (T3) and thyroxine (T4) showed a significant decrease while the thyroid stimulating hormone showed an increase. Thyroid dysfunction was accompanied by alteration in liver function enzymes and a state of hyperlipidaemia, SP treatment has significantly decreased oxidative stress and caspase-3 activity in thyroid tissues, which was accompanied by a significant improvement in the level of thyroid hormones, liver functions and lipid profile. SP may be a useful adjunct to attenuate thyroid disorders associated with liver dysfunction and dyslipidaemia in irradiated rats by its free radical scavenging and potent antioxidant activity.

MicroRNA-122 expression in hepatotoxic and γ-irradiated rats pre-treated with naringin and silymarin

Recently, the fundamental roles of microRNAs (miRNAs) in the progression and development of diseases have been shown in several studies. In the liver 70% of all expressed miRNAs is miR-122; therefo...

Studying the Ameliorative Effect of Bee Venom Against Damage and Inflammation Induced in Gamma-Irradiated Rats

The aim of this study was focused on investigating the possible protective effect of Bee Venom (BV) against gamma radiation induced damage and inflammation in male rats. Gamma-irradiation (6 Gy) resulted in a significant elevation in the level of tumor necrotic factor-alpha (TNF-α) , interleukin-6 (IL-6) , creatinine kinase-MB (CK-MB) and cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), serum aspartate transaminase (AST) and alanine transaminase (ALT) , serum glucose, malondialdehyde (MDA) concentration and xanthine oxidase activity associated with remarkable decrease in insulin level, glutathione content (GSH) and the activity of xanthine dehydrogenase (XDH), superoxide dismutase (SOD) and catalase (CAT) in heart and liver tissues compared to control group. Injection of BV (5ml/kg b. wt. / day/6weeks) to γ-irradiated rats was found to offer protection against γ-irradiation induced oxidative stress and significantly ameliorated the changes occurred in the above investigated biochemical parameters. It could be concluded that Bee venom clarified a modulatory role against gamma radiation induced oxidative damage and inflammation in the heart and liver tissues.

Concerted effects of L-carnitine and vitamin E on cardio-pulmonary apoptosis induced by gamma irradiation in rats

Pulmonary fibrosis and cardiotoxicity are a common and dose-limiting side-effect of ionizing radiation used to treat cancers of the thoracic region. This study aims at investigating the role of Bcl-2, Bax protein and caspase-3 in the pathogenesis of tissue damage induced by gamma irradiation (IRR) and the protective potential role of vitamin E (Vit E) and/or L-carnitine (L-car) against γ-irradiation induced oxidative injury. Irradiation was performed as a whole body γ-irradiation (5Gy). Immnuohistochemistry was used to estimate Bcl-2 expression. The level of Bax and caspase 3 activity were determined using enzyme-linked immunosorbent assay. C-reactive protein was determined using immunoturbidimetric assay. Results revealed that γ-irradiation (5Gy) induced apoptosis via the mitochondrial pathway by downregulating Bcl-2 expression, upregulating Bax protein and activating caspase-3. Administration of Vit E (50mg/kg) and/or L-car (300mg/kg) prior to gamma-irradiation decreased apoptosis through changing the expression of Bcl-2, Bax and caspase-3 activity. Exposure to γ-irradiation increased triglyceride, cholesterol, low density lipoprotein-cholesterol (LDL-C), C-reactive protein (CRP) and potassium levels, creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities and decreased high density lipoprotein-cholesterol (HDL-C) levels. The altered lipid profile, CRP and potassium levels, CK-MB and LDH activities induced by exposure to γ-irradiation were significantly renovated in Vit E and/or L-car pretreated γ-irradiated rats. In conclusion, Vit E and/or L-car might ameliorate γ-irradiation induced apoptosis via modulation of Bcl-2, Bax and caspase-3.

Blueberry extract attenuates γ-radiation-induced hepatocyte damage by modulating oxidative stress and suppressing NF-κB in male rats.

Radiation exposure is known to produce many harmful effects in biological systems, and these effects are often mediated by oxygen free radicals. Because blueberries are rich in antioxidant compounds such as anthocyanins and phenolic acids, we divided forty adult rats into four treatment groups of 10 (G1–4) as follows: G1 rats were used as a control, G2 rats were irradiated with 8 Gy at 2 Gy/week at a dose rate of 0.5 Gy/min, G3 rats were administered blueberry extract (200 mg/kg) and G4 rats were administered blueberry extract during the same irradiation period. In subsequent determinations, γ-irradiated rats had increased levels of cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL), and significantly elevated liver enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and total bilirubin. In contrast, significant reductions in albumin, total protein and globulin were observed, whereas gamma irradiation decreased activities of the antioxidant enzymes glutathione (GSH), catalase (CAT), xanthine dehydrogenase (XDH) and superoxide dismutase (SOD). We also observed incremental increases in DNA fragmentation percentages and histopathological changes in liver tissues. Serum pro-inflammatory cytokine levels (IL-6, IL-10 and TNF-α) were significantly elevated and hepatic NF-кB was upregulated. In G4 rats, treatments with blueberry extract restored liver pro-oxidant status, reduced cytokine levels, ameliorated histopathological parameters and reduced DNA damage. In conclusion, γ-radiation exerts toxic effects in the rat livers, and blueberry extract is protective against these.

Cicer arietinum extract ameliorate γ-irradiation disorders via modulation of oxidative/antioxidative pathway

Ionized radiations trigger thoughtful adverse hazards through multiple organ dysfunctions. Recently, antioxidant-based biodrugs are used to prevent and treat ionizing radiation hazards. The present study aimed to investigate the prospective ameliorative effect of Cicer arietinum extract (CAE) against γ-irradiation and the pathway of this amelioration in male albino rats. Twenty four rats were allocated into four groups; (i) control group, (ii) CAE group in which rats treated with a dosage of 500 mg CAE/kg b.wt, (iii) γ-irradiated group in which rats exposed to 6Gy γ-irradiation, (iv) γ-irradiated+CAE group; rats of this group treated with CAE 1 h post exposure. All rats treated for 21 days. Liver, kidney and femoral bone were rapidly excised and homogenized for the biochemical analysis. Energy dispersive X-ray (EDX) and inductively coupled plasma emission spectrometer (ICP) analyses exhibit that γ-irradiation elicits significant change in the essential trace elements content in liver, kidney, and bone. Further, significant increases in TBARS and H2O2 contents accompanied by significant decreases in GSH, SOD, CAT, and GPx activities in liver, kidney and bone tissues were recorded in the γ-irradiated rats compared to control group. Additionally, marked reduction in the thickness of cortical bone was recorded in rats exposed to γ-irradiation. Conversely, CAE (500 mg/kg b.wt, p.o) administration for 21 days to γ-irradiated rats effectively reverses most of the altered parameters of the γ-irradiated rats. In conclusion, the present findings suggested that CAE is a potential agent that can be used against radiation hazards. This effect may be owing to its antioxidant mechanism, as CAE has an inhibitory effect against hydrogen peroxide (H2O2) and superoxide radical (O2·−) beside its ferric reducing antioxidant power (FRAP). This finding recommended that CAE can be utilized clinically to mitigate ionized radiation-induced hazard effects.

Beneficial Effects of Piperine in global cerebral ischemia/reperfusion model in irradiated rats

Stroke is the third cause of death and a leading cause of chronic disability all around the world. Inflammation and oxidative stress are common pathogenic pathways of brain injury induced by ischemia/reperfusion (I/R). This work aims to investigate the possible role of Piperine as antioxidant and anti-inflammatory in attenuating the cerebral ischemia/reperfusion (I/R)-induced brain injury in whole body γ-irradiated rats. Global cerebral ischemia was induced in both irradiated and non-irradiated male Wistar rats, and was followed by reperfusion. The beneficial effect of pretreatment with piperine (10 mg/kg, once daily p.o. for 15 days) was examined on cerebral ischemia-induced brain injury in 24 h pre-irradiated (6 Gy) male Wistar rats. I/R increased brain content of malondialdehyde (MDA) and decreased its glutathione (GSH) content and total antioxidant capacity (TAC). It also raised serum lactate dehydrogenase (LDH) activity and brain cytosolic calcium (Ca2+) level. Pre-treatment with piperine significantly attenuated brain injury in I/R irradiated rats by decreasing cytosolic brain calcium level and serum lactate dehydrogenase (LDH) activity. In addition, a significant decrease in nuclear factor kappa-B (NF-kB) was recorded in piperine treated group. These findings indicate that administration of piperine ameliorated most of the tested biochemical changes induced by I/R in irradiated rat brain and serum.

PROPHYLACTIC ROLE OF SOME MEDICAL HERBS AGAINST GAMMA RADIATION INDUCED BIOCHEMICAL DISTURBANCE IN THE LIVER AND CARDIAC FUNCTIONS OF RATS.

The objective of this study was to evaluate the ability of ginseng, green tea or/and cinnamon to improve the disturbances occur in liver, heart, lipid and thyroid profiles as well as antioxidant and lipid peroxidation status in rats as a result of exposure to γ-irradiation. The obtained results revealed a significant (p < 0.05) increase in serum alanine transferase (ALT), aspartate transferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) activities as well as elevations in the levels of total cholesterol, triglycerides, high density cholesterol (HDL-Ch) and low density cholesterol (LDL-Ch) in irradiated rats than those in control ones. On the other hand, the concentrations of serum total protein, albumin and free triiodothyronine (FT3) were remarkable decreased in rats as a result of exposure to γ-irradiation. Moreover, as a result of exposure to γ-radiation, the mean value of GSH content and Gpx activity were remarkable decreased in both the liver tissues and in the cardiac tissues of the rats. On the contrary, the exposure to γ-radiation caused a significant (P<0.001) increment in thiobarbituric acid reactive substance (TBARS) level in both liver and heart tissues of rats. When γ-irradiated rats groups were treated with ginseng, green tea or cinnamon, considerable amelioration effects in all previous studied parameters were pronounced dependent on time of treatment (15 & 30 days). The maximum correction was occurred in all studied parameters in irradiated-rats treated with mixture of ginseng, green tea and cinnamon dependent on the time of treatment (15 and 30 days). So, this study can practically help to encourage the clinical use of this mixture as a treatment for exposure to γ-radiation. These mechanisms were discussed according to available recent researches.

Anti-apoptotic role of spermine against lead and/or gamma irradiation-induced hepatotoxicity in male rats.

Exposure to either lead (Pb) or γ-irradiation (IR) results in oxidative stress in biological systems. Herein, we explored the potential anti-apoptotic effect of spermine (Spm) against lead and/or γ-irradiation-induced hepatotoxicity in male albino rats. Rats were divided into eight experimental groups of ten rats each: groups including negative control, whole body γ-irradiated (6Gray (Gy)), lead acetate (PbAct) trihydrate orally administered (75mg/kg bw≡40mg/kg bw Pb for 14 consecutive days), and Spm intraperitoneally dosed (10mg/kg bw for 14 consecutive days) rats and groups subjected to combinations of Pb+IR, Spm+IR, Spm+Pb, and Spm+Pb followed by IR on day 14 (Spm+Pb+IR). A significant decrease in arginase activity as well as mRNA and protein levels of Bcl-2 and p21 was observed in rats intoxicated with Pb and/or γ-irradiation compared to controls, whereas Bax mRNA and protein levels were significantly increased. Also, an increased level of nitric oxide (NO) with a reduced arginase activity was observed in liver tissues of intoxicated rats. Spm co-treatment with lead and/or γ-irradiation attenuated the increase in Bax mRNA and protein expression, while it restored those of Bcl-2 and p21 together with NO levels and arginase activity to control values. Altogether, we suggest that Spm may be useful in combating free radical-induced apoptosis in Pb-intoxicated and/or γ-irradiated rats.

Role of Annona muricata (L.) in oxidative stress and metabolic variations in diabetic and gamma-irradiated rats

A. muricata L., commonly known as graviola, is a plant widely distributed throughout the world rich in phytochemicals and minerals. The objective of this study was to investigate the influence of A.muricata on oxidative stress in the liver, kidney and pancreas along with variations in glucose, insulin, lipid profile, liver and kidney functions in diabetic (DM) and γ-irradiated rats (IRR). Diabetes was induced by a single intraperitoneal injection of streptozotocin (65 mg/Kg body weight). Irradiation was performed as whole body γ-irradiation (5 Gy) administered in a single acute dose. A.muricata leaves aqueous extract (100 mg/Kg body weight) was administered via gavages during 2 weeks to diabetic rats or during 2 weeks before γ-irradiation. Diabetic rats received A. muricata during 2 weeks before irradiation. Animals were sacrificed 24 hours post irradiation and/or A. muricata trearment. A. muricata treatment has significantly attenuated hyperglycemia, hypoinsulinemia and dyslipidemia, and reduced the increase of serum alanine and aspartate amino transferase activities and serum urea and creatinine levels. The amelioration in metabolic variations was associated to significant improvement of oxidative stress in tissues notified by a higher superoxide dismutase (SOD) activity and glutathione (GSH) content and a lower malondialdehyde (MDA) content. It could be suggested that the synergistic relationship between the different elements found in the leaf of A.muricata could be beneficial in ameliorating liver and kidney function and correcting metabolic variations associated with oxidative stress in the liver, kidney and pancreas.

Curative role of pantothenic acid in brain damage of gamma irradiated rats.

Radiation induced brain damage is associated with impairment of mitochondrial functions, variations in the level of neurotransmitters, and oxidative stress. Mitochondrial function is closely linked to the level of neurotransmitters since the precursors are supplied by the Kreb's cycle intermediates. The objective of this study was to evaluate the influence of pantothenic acid, an essential component in the synthesis of Coenzyme A (CoA), on the activity of the Krebs cycle enzymes, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), and succinate dehydrogenase (SDH); the level of aspartic, glutamic and GABA; the activity of transaminases, and oxidative stress, in the cerebrum of γ-irradiated rats. Pantothenic acid (26mg/Kg) was orally administered to the rats, 2h after irradiation and during the following 5days. Animals were sacrificed the 7th day post-irradiation. The exposure of male albino rats to γ-rays (5Gy) has triggered oxidative stress notified by a significant elevation in the level of malondialdehyde (MDA), an end product of lipid peroxidation, associated to a significant decrease in the content of phospholipids, and the antioxidant compound glutathione (GSH). The activity of IDH, α-KGDH, and SDH, has significantly decreased, while the level of aspartic, glutamic and GABA has significantly increased. In parallel to these changes, the activity of alanine and aspartate transaminase has significantly increased, compared to their values in the control rats. Pantothenic acid treatment, has significantly attenuated oxidative stress; enhanced the activity of IDH, α-KGDH, and SDH; minimized the increase in the level of amino acids and the activity of transaminases, compared to their values in the cerebrum of irradiated rats. In conclusion, pantothenic acid could improve the level of neurotransmitters amino acids, which depends on the enzymatic activities of Krebs cycle and linked to oxidative stress.