Anticancer effect of propranolol on diethylnitrosamine-induced hepatocellular carcinoma rat model.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non-selective ß-blocker propranolol demonstrated antiproliferative activity in many cancer types. OBJECTIVE: This investigation aimed to evaluate the anticancer effect of propranolol against DEN-induced HCC in rats. METHODS: Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10 weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10 weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks. RESULTS: HCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-fetoprotein (AFP), total- and direct-bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF-1α, IL-8, NF-κB, PGE2, TGF-ß1, VEGF, and CD8, but significant decline of GSH, and IL-10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG-3 were up-regulated. Moreover, the protein expression of p-PKC was up-regulated, while that of PD-1 and PD-L1 were down-regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group. CONCLUSION: Propranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD-1/PD-L1 and LAG-3 signals participated in the anti-tumor effect of propranolol on HCC.

Protective effect of chicory and/or artichoke leaves extracts on carbon tetrachloride and gamma-irradiation-induced chronic nephrotoxicity in rats.

The prevalence of chronic kidney disease (CKD) is in progress that causes kidney failure, leading to global problems. This manuscript investigated the nephroprotective effects of chicory (CLE) and/or artichoke (ALE) leaves extracts on carbon tetrachloride (CCl4 ) and gamma-irradiation (Rad)-induced chronic nephrotoxicity in rats. Rats were divided into 10 groups (10 animals/group): group 1: control, groups 2-7 rats were treated with CLE, ALE, CLE/ALE, CCl4 , Rad, and CCl4 /Rad, respectively. Groups 8 to 10, rats were intoxicated with CCl4 /Rad, and treated with CLE, ALE, and CLE/ALE extracts, respectively, for 4 weeks. The data demonstrated that CCl4 administration or Rad exposure induced high levels of urea and creatinine, with low levels of total protein and albumin in the serum. However, high levels of malondialdehyde (MDA), nitric oxide (NO), hydrogen peroxide (H2 O2 ), some pro-inflammatory markers such as interleukins (IL-1ß, IL-2, IL-6), TNF-α, NF-κB, the fibrotic marker; TGF-ß1, calcium, and copper, low contents of reduced glutathione (GSH), iron, and zinc, and suppression of the antioxidant enzymes' activity, superoxide dismutase (SOD), and catalase (CAT) were observed. In addition, the Wnt and ß-catenin protein expression ratios were up-regulated in the kidney tissues of the CCl4 , and Rad intoxicated animals. However, the combined treatment CCl4 /Rad augmented these measurements. On the other hand, CLE, ALE, and CLE/ALE treatments demonstrated nephroprotection in the kidney tissues of CCl4 /Rad intoxicated animals, in the order of CLE/ALE>ALE>CLE by ameliorating the investigated parameters. Kidney tissues' histopathological examinations confirmed these results. In conclusion, CLE and/or ALE demonstrated nephroprotection against CCl4 /Rad co-toxicity mediated by down-regulation of renal Wnt/ß-catenin protein expressions.

Rutin protects against gamma-irradiation and malathion-induced oxidative stress and inflammation through regulation of mir-129-3p, mir-200C-3p, and mir-210 gene expressions in rats' kidney.

Kidney injury represents a global concern, leading to chronic kidney disease. The organophosphate insecticide malathion (MT) demonstrates environmental disturbance and impairment of different mammalian organs, including kidneys. Likewise, gamma-irradiation (IRR) provokes destructive effects in the kidneys. Rutin is a flavonoid glycoside that exhibits nephro-protective and radio-protective properties. This manuscript focused on investigating the protective response of rutin on MT- and IRR-triggered kidney injury in rats. Rats were randomly divided into eight groups of twelve: G1 (C), control; G2 (Rutin), rutin-treated rats; G3 (IRR), gamma-irradiated rats; G4 (MT), malathion-treated rats; G5 (IRR/MT), gamma-irradiated rats treated with malathion; G6 (IRR/Rutin), gamma-irradiated rats treated with rutin; G7 (MT/Rutin), rats treated with malathion and rutin; and G8 (IRR/MT/Rutin), gamma-irradiated rats treated with malathion and rutin, every day for 30 days. The results demonstrated that rutin treatment regulated the biochemical parameters, the oxidative stress, the antioxidant status, and the inflammatory responses due to the down-regulation of the renal NF-κB p65 protein expression. Moreover, it amended the activity of acetylcholinesterase (AchE), angiotensin ACE I, and ACE II-converting enzymes. Besides, it regulated the iNOS, eNOS, miR-129-3p, miR-200c, and miR-210 gene expressions and bradykinin receptor (B1R and B2R) protein expressions. Histopathological examinations of the kidney tissue confirmed these investigated results. It could be concluded that rutin demonstrated nephro/radioprotection and counteracted the toxicological effects triggered in the kidney tissues of IRR, MT, and IRR/MT intoxicated rats, via regulating miR-129-3p, miR-200c-3p, and miR-210-3p gene expressions, which consequently regulated B2R protein expressions, ACE II activity, and HIF-1α production, respectively.

Protective impact of Spirulina platensis against γ-irradiation and thioacetamide-induced nephrotoxicity in rats mediated by regulation of micro-RNA 1 and micro-RNA 146a.

Chronic kidney disease develops popular and medical health problems, especially in developing countries. The objective of this study is to investigate the protective mechanism of Spirulina platensis against γ-irradiation (R) and/or thioacetamide (TAA)-induced nephrotoxicity in rats. Rats intoxicated with R or TAA showed alterations in kidney function markers (urea, creatinine, albumin, and total protein contents), oxidative stress markers (malondialdehyde, reduced glutathione), antioxidant enzymes (superoxide dismutase, catalase), and several inflammatory markers (including, the high-sensitivity C-reactive protein, hypoxia-inducible factor-1 alpha, tumor necrosis factor-alpha, interferon-gamma, some interleukins, and nuclear factor-kappa B). Rats also acquired apoptosis, evinced by high caspase-3 efficacy. This nephrotoxicity mediated by upregulation of the messenger RNA (mRNA) gene expression of the autophagy markers: Beclin-1, microtubule-associated protein LC3, p62 binding protein, immunoglobulin G receptor Fcγ receptor (FcγR), micro-RNA-1 (miR-1), protein expression of phospho-adenosine monophosphate-activated protein kinase, and phospho-mammalian target of rapamycin, along with downregulation of miR-146a mRNA gene expression and alteration of calcium and iron levels. The combined treatment R/TAA enhanced the observed oxidative stress, inflammation, apoptosis, and autophagy that mediated by higher upregulation of miR-1 and downregulation of miR-146a mRNA gene expression. Spirulina platensis administration exhibited a nephroprotective impact on R, TAA, and R/TAA toxicities via regulating miR-1 and miR-146a mRNA gene expression that monitored adenosine monophosphate-activated protein kinase/mammalian target of rapamycin signaling.

Antitumor and Radiosensitizing Effects of Zinc Oxide-Caffeic Acid Nanoparticles against Solid Ehrlich Carcinoma in Female Mice.

This study aimed to evaluate the anticancer and radio-sensitizing efficacy of Zinc Oxide-Caffeic Acid Nanoparticles (ZnO-CA NPs). ZnO-CA NPs were formulated by the conjugation of Zinc Oxide nanoparticles (ZnO NPs) with caffeic acid (CA) that were characterized by Fourier Transform Infrared Spectra (FT-IR), X-ray Diffractometer (XRD), and Transmission Electron Microscopy (TEM). In vitro anticancer potential of ZnO-CA NPs was evaluated by assessing cell viability in the human breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines. In vivo anticancer and radio-sensitizing effects of ZnO-CA NPs in solid Ehrlich carcinoma-bearing mice (EC mice) were also assessed. Treatment of EC mice with ZnO-CA NPs resulted in a considerable decline in tumor size and weight, down-regulation of B-cell lymphoma 2 (BCL2) and nuclear factor kappa B (NF-κB) gene expressions, decreased vascular cell adhesion molecule 1 (VCAM-1) level, downregulation of phosphorylated-extracellular-regulated kinase 1 and 2 (p-ERK1/2) protein expression, DNA fragmentation and a recognizable peak at sub-G0/G1 indicating dead cells' population in cancer tissues. Combined treatment of ZnO-CA NPs with γ-irradiation improved these effects. In conclusion: ZnO-CA NPs exhibit in-vitro as well as in-vivo antitumor activity, which is augmented by exposure of mice to γ-irradiation. Further explorations are warranted previous to clinical application of ZnO-CA NPs.

Biochemical study on the protective effect of curcumin on acetaminophen and gamma-irradiation induced hepatic toxicity in rats.

Acetaminophen (APAP) is one of the few recommended analgesic and antipyretic drugs in some critical cases such as viral disease COVID-19. However, the unrestricted use of APAP develops liver disorders. Hepatotoxicity and liver injury can also be induced by ionizing radiation (IR) during radiotherapy. The data of the current study represents that treatment of rats with either APAP-overdose, or gamma-irradiation (R) induces hepatotoxicity, results in significant increases of the hepatic-enzymes activities (ALT, AST, ALP, GGT, LDH, and MDH), as well as enhancement of triglycerides, total cholesterol levels, combined with declines in albumin and total protein contents. An enhancement of the lipid peroxides (malondialdehyde; MDA), and nitric oxide levels along with a decline of reduced glutathione contents and suppression of superoxide dismutase, catalase, and glutathione peroxidase activities are also observed within the liver tissues of intoxicated animals. TNF-α, IL-1ß, IL-6, iNOS, Cytochrome P450 2E1 (CYP2E1), miR-802 gene expression, NF-κB, and calcium levels are up-regulated, while Nuclear factor erythroid-related factor-2 (Nrf2), Hemoxygenase-1 (HO-1) protein and gene expressions, as well as, glutamate-cysteine ligase catalytic subunit (GCLC), NAD(P)H-Quinone oxidoreductase (NQO1), and miR-122 gene expressions are down-regulated in the livers of intoxicated animals. All these parameters show significant improvement in R/APAP intoxicated animals. Curcumin pretreatment develops an amelioration of these effects in APAP-overdose, R-exposure, or R/APAP treatments. In conclusion, oral administration of curcumin shows hepatoprotective effects against APAP-overdose induced hepatic damage in normal and gamma-irradiated rats through prospective regulation of the therapeutic targets CYP2E1, Nrf2, and NF-κB, via organizing the miR-122 and miR-802 gene expression.

Nicotine encourages oxidative stress and impairment of rats' brain mitigated by Spirulina platensis lipopolysaccharides and low-dose ionizing radiation.

Nicotine is a psychoactive alkaloid of tobacco, which is ingested during cigarettes or electronic cigarette smoking. Extensive consumption of nicotine induced oxidative stress. Accordingly, it is implicated in many pathophysiology brain disorders and triggers neurodegeneration. In this study, we investigated the protective role of Spirulina platensis-lipopolysaccharides (S.LPS) and the low dose-ionizing radiation (LD-IR) against the induced neurotoxicity in the rats' brain due to the prolonged administration of high nicotine levels. Rats treated with nicotine for two months showed alterations in the oxidative stress markers (malondialdehyde (MDA), reduced glutathione (GSH) and oxidized glutathione disulfide (GSSG)), antioxidant enzymes (superoxide dismutase (SOD), catalase (Cat), glutathione enzymes (GPx and GST)) as well as several pro-inflammatory markers (Tumor Necrosis Factor-alpha (TNF-α), Interleukin-17 (IL-17), and Nuclear Factor-kappa B (NF-κB)), and induced apoptosis through Caspase-3 activity. Nicotine also upregulated the mRNA gene expression of cytochrome P450 enzymes (CYP2B1 and CYP2E1), Cyclin-dependent kinase 5 (CDK5), Toll-Like Receptor 4 (TLR4), and phospho-Tau (p-Tau) protein expression. Besides, it downregulated the alpha-7 nicotinic receptor (α7nAChR) mRNA gene expression accompanied by a decline in the calcium (Ca2+) level. S.LPS exhibited antioxidant, anti-inflammatory, anti-apoptotic and neuroprotective activities, which counteracting the detrimental effects of chronic nicotine administration. LD-IR demonstrated comparable effects to S.LPS. Exposure of rats to LD-IR enhanced the neuroprotective effects of S.LPS against nicotine toxicity. The light microscopic examination of the brain tissues was in agreement with the biochemical investigations. These findings display that S.LPS and LD-IR mitigated the oxidative stress and the impairment of rats' brain induced by nicotine, due to regulation of the mRNA gene expression of cytochrome P450 enzymes (CYP2B1 and CYP2E1) and the signaling pathway of Tau protein phosphorylation.

Modulatory effects of new curcumin analogues on gamma-irradiation - Induced nephrotoxicity in rats.

In the present study, a new series of 2-amino-pyran-3-carbonitrile derivatives of curcumin 2-7 have been synthesized via one-pot simple and efficient protocol, involving the reaction of curcumin 1 with substituted-benzylidene-malononitrile to modify the 1,3-diketone moiety. The structures of the synthesized compounds 2-7 were elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. The nephroprotective mechanism of these new curcumin analogues was evaluated on the post-gamma-irradiation (7 Gy) - induced nephrotoxicity in rats. Activation of Nrf2 by these curcumin analogues is responsible for the amendment of the antioxidant status, impairment of NF-κB signal, thus attenuate the nephrotoxicity induced post-γ-irradiation exposure. 4-Chloro-phenyl curcumin analogue 7 showed the most potent activity. In conclusion, the results of the present study demonstrate a promising role of these new curcumin analogues to attenuate the early symptoms of nephrotoxicity induced by γ-irradiation in rats via activation of Nrf2 gene expression. These new curcumin analogues need further toxicological investigations to assess their therapeutic index.

Novel amino acid derivatives bearing thieno[2,3-d]pyrimidine moiety down regulate NF-κB in γ-irradiation mediated rat liver injury.

A series of different amino acid-bearing thieno[2,3-d]pyrimidine moiety was synthesized via green chemistry aspects incorporating water as a solvent to give 2a-f, which were then acidified to attain the target compounds 3-9. Moreover, a tricyclic imidazothienopyrimidine of the glycine derivative (3) was synthesized to give (10). The title compounds were characterized by FT-IR, Mass, 13C-1HNMR spectroscopy and microanalysis. All the obtained amino acid-derivatives were screened for their post-irradiation protective efficacy in young rats. γ-Irradiation exposure was employed to induce oxidative stress. Radiation triggered significant alterations in the hematologic and blood - biochemical parameters. Further, a significant deterioration of hepatic antioxidant status was observed. Furthermore, a significant elevation of Nuclear Factor-kappa B (NF-κB) protein expression and level, which induced elevation in Cyclooxygenase-2 (COX-2) activity and cytochrome P450 2E1 (CYP2E1) gene expression were detected in hepatic tissues. Additionally, elevated levels of Tumor Necrosis Factor-alpha (TNF-α), and Interleukin-6 (IL-6) were perceived in serum of γ-irradiated young rats. However, most of the newly synthesized derivatives showed significant protective effects against injuries induced by γ-irradiation exposure, via ameliorating the altered hematopoietic system and activity of different biochemical parameters in blood. The results indicate that the antioxidant and anti-inflammatory mechanism of these compounds could be attributed to the significant down-regulation NF-κB protein expression in hepatic tissues. Subsequently, NF-κB could regulate TNF-α and IL-6 levels, COX-2 activity and CYP2E1 gene expression. Methionine derivative 8 was found to be the most active one. CONCLUSION: These new amino acid-derivatives showed promising outcomes as curative agents against γ-irradiation induced oxidative stress and physiological disturbance in different organs of young animals. Beyond, they may represent a novel selective class for treating liver injury induced by γ-irradiation in young rats, via down-regulation of NF-κB expression. Further investigations are warranted prior to the clinical use of these new compounds.

Radio-protective effect of some new curcumin analogues.

In the present study, novel symmetrical curcumin analogues (2-7) have been synthesized by substituting the phenolic OH of curcumin with different linkers providing additional keto-enol tautomerism, very essential for radioprotective activity. The structures of the synthesized compounds (2-7) were elucidated by elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found consistent with the assigned structures. The curative effect of these new compounds, against the oxidative stress due to exposure of rats to the whole body γ-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited elevations of ALT, AST activities, urea, creatinine, triglycerides, total cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Nuclear Factor-kappa B (NF-κB) levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Treatment of gamma-irradiated rats with the new curcumin analogues (2-7) showed significant amelioration in the in-vivo antioxidant status, liver and kidney functions, as well as the anti-inflammatory markers (IL-6, TNF-α and NF-κB). Inhibition of NF-κB could be responsible for the improvement of the antioxidant and anti-inflammatory status in gamma-irradiated animals, by down-regulation of IL-1ß and TNF-α level. In conclusion, the new curcumin analogues (2-7) exhibited post-protective effect on gamma-irradiation, by NF-κB inhibition.

Modulation of gamma-irradiation and carbon tetrachloride induced oxidative stress in the brain of female rats by flaxseed oil.

The activity of flaxseed oil (FSO) on gamma-irradiation (7Gy) and/or carbon tetrachloride (CCl4) induced acute neurotoxicity in rats' brain was investigated. The results revealed a significant decrease (p<0.05) in superoxide dismutase (SOD), catalase (CAT), glutathione-peroxidase (GSH-Px) activities, reduced glutathione (GSH) and manganese (Mn) contents. Further, a significant elevation (p<0.05) in malondialdehyde, nitric oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1-beta (IL-1ß), Interleukin-6 (IL-6), transforming growth factor-beta-1 (TGF-ß1), iron (Fe), calcium (Ca), copper (Cu) and magnesium (Mg) levels were observed. Furthermore, the relative ratio of xanthine oxidase (XO) and inducible nitric-oxide synthase (iNOS) gene expression levels were elevated in the brain tissues of γ-irradiated and CCl4 intoxicated animals. Those effects were augmented due to the effect of CCl4-induced toxicity in γ-irradiated rats. The treatment of FSO displayed significant amendment of the studied parameters in the brain tissues of γ-irradiated and CCl4 intoxicated animals. FSO has a neuroprotective effect against CCl4-induced brain injury in gamma-irradiated rats. This effect is interrelated to the ability of FSO to scavenges the free radicals, enhances the antioxidant enzymes activity, increases GSH contents, down-regulates the inflammatory responses, ameliorates the iron, calcium, copper, magnesium, manganese levels and inhibiting the gene expression level of XO and iNOS in the brain tissues of intoxicated animals. In conclusion, this study demonstrated that the potent antioxidant and anti-inflammatory activities of FSO have the ability to improve the antioxidant status, suppress the inflammatory responses, and regulate the trace elements in the brain tissues of γ-irradiated, CCl4, and their combined effect in intoxicated animals. Consequently, FSO exhibited neuroprotective activity on γ-irradiated, CCl4, and their combined effect induced brain injury in rats.

Hepatoprotective effect of grape seed oil against carbon tetrachloride induced oxidative stress in liver of γ-irradiated rat.

Carbon tetrachloride (CCl4) and ionizing radiation are well known environmental pollutants that generate free radicals and induce oxidative stress. The liver is the primary and major target organ responsible for the metabolism of drugs, toxic chemicals and affected by irradiation. This study investigated the effect of grape seed oil (GSO) on acute liver injury induced by carbon tetrachloride (CCl4) in γ-irradiated rats (7Gy). CCl4-intoxicated rats exhibited an elevation of ALT, AST activities, IL-6 and TNF-α level in the serum. Further, the levels of MDA, NO, NF-κB and the gene expression of CYP2E1, iNOS and Caspase-3 were increased, and SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Furthermore, silent information regulator protein 1 (SIRT1) gene expression was markedly down-regulated. Additionally, alterations of the trace elements; copper, manganese, zinc and DNA fragmentation was observed in the hepatic tissues of the intoxicated group. These effects were augmented in CCl4-intoxicated-γ-irradiated rats. However, the administration of GSO ameliorated these parameters. GSO exhibit protective effects on CCl4 induced acute liver injury in γ-irradiated rats that could be attributed to its potent antioxidant, anti-inflammatory and anti-apoptotic activities. The induction of the antioxidant enzymes activities, down-regulation of the CYP2E1, iNOS, Caspase-3 and NF-κB expression, up-regulation of the trace elements concentration levels and activation of SIRT1 gene expression are responsible for the improvement of the antioxidant and anti-inflammatory status in the hepatic tissues and could be claimed to be the hepatoprotective mechanism of GSO.

Fermentation enhances Ginkgo biloba protective role on gamma-irradiation induced neuroinflammatory gene expression and stress hormones in rat brain.

UNLABELLED: Ionizing radiation has attracted a lot of attention due to its beneficial and possible harmful effects to the human population. The brain displays numerous biochemical and functional alterations after exposure to irradiation, which induces oxidative-stress through generation of reactive oxygen species (ROS). The present study evaluated the neuro-protective role of fermented Ginkgo biloba (FGb) leaf extract, compared to non-fermented G. biloba (Gb) leaf extract against γ-irradiation (6Gy) in the rats' brain. The changes of the Gb phytochemical constituents after fermentation, using Aspergillus niger were evaluated by Gas Chromatography-Mass Spectrometry. The results showed a significant decrease in superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and elevation of the calcium level in the brain cytosolic fraction of γ-irradiated rats. Further, significant increases in the malondialdehyde (MDA), the stress hormones (catecholamines); epinephrine (EN), norepinephrine (NE) and dopamine (DA) levels and the interleukin-1-beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) gene expression relative ratio in parallel with a significant decrease in the glutathione (GSH) content and DNA fragmentation in the brain tissues of the γ-irradiated rats were observed. The pre-treatment with Gb extract significantly amended these biochemical parameters. Meanwhile, the pre-treatment with the FGb showed more improvement, compared to Gb, of these biochemical parameters in the brain of γ-irradiated rats, which could be attributed to the enhancement of its antioxidant activity after fermentation. These findings suggested that fermentation enhances the protective effect of Gb in the brain on the neuroinflammation, release of the stress hormones, apoptosis and oxidative damage induced by γ-irradiation. IN CONCLUSION: fermentation improved the bio-activities of Gb leaf extract and thus enhanced the in-vivo antioxidant, anti-apoptotic and anti-inflammatory activities, leading to amelioration of the stress hormones and Ca level. Accordingly, the fermentation enhances the protective role of Gb against γ-irradiation induced physiological disturbance in the rat's brain.

Protective mechanism of grape seed oil on carbon tetrachloride-induced brain damage in γ-irradiated rats.

This study investigated the possible beneficial effects of grape seed oil (GSO) on carbon tetrachloride (CCl4)-induced acute neurotoxicity in γ-irradiated rats. A statistical significant decrease in superoxide-dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GPx) activities and reduced glutathione (GSH) content were exhibited. Further, a significant elevation in malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor-beta-1 (TGF-ß1) levels was observed. Furthermore, xanthine oxidase (XO) and inducible nitric oxide synthase (iNOS) gene expression were elevated in the γ-irradiated animals treated with an acute dose of CCl4. The pretreatment of GSO exerts significant amelioration of the studied parameters. In conclusion, this study demonstrated that GSO has a neuroprotective effect against CCl4-induced brain injury in γ-irradiated rats, which is likely attributed to its ability to scavenge the free radicals, suppress the inflammatory responses, improve the activity of the antioxidant enzymes and inhibit the XO and iNOS gene expression levels.

Gastroprotective effect of kefir on ulcer induced in irradiated rats.

The current study was designed to investigate the protective effect of kefir milk on ethanol-induced gastric ulcers in γ-irradiated rats. The results of the present study revealed that treatment with γ-irradiation and/or ethanol showed a significant increase in ulcers number, total acidity, peptic, H(+)K(+)ATPase, MMP-2 and MMP-9 activities and MDA level, which were accompanied by a significant decrease in the mucus content, the stomach GSH level, the GSH-Px activity and DNA damage. Pre-treatment with kefir milk exert significant improvement in all the tested parameters. Kefir milk exerts comparable effect to that of the antiulcer drug ranitidine. In conclusion, the present study revealed that oral administration of kefir milk prevents ethanol-induced gastric ulcer in γ-irradiated rats that could attribute to its antioxidant, anti-apoptotic and radio-protective activities.

Photodynamic therapy mediated antiproliferative activity of some metal-doped ZnO nanoparticles in human liver adenocarcinoma HepG2 cells under UV irradiation.

Photodynamic therapy (PDT) is a promising new modality for the treatment of cancer through generation of reactive oxygen species (ROS). In this work, human liver adenocarcinoma cells HepG2 were treated with zinc oxide nanoparticles (ZnO-NPs), metal-doped-ZnO-NPs: Fe-ZnO-NPs Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs, Silica-coated ZnO-NPs, titanium dioxide nanoparticles (TiO2-NPs), titanium dioxide nano-tubes (TiO2-NTs) and ZnO-NPs/TiO2-NTs nanocomposite under UV irradiation. Doxorubicin was used as a standard drug. The results demonstrated that the ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs showed cytotoxicity against HepG2 cells, with the median growth inhibitory concentrations (IC50) 42.60, 37.20, 45.10, 77.20 and 56.50 µg/ml, respectively, as compared to doxorubicin (IC50: 20.10 µg/ml). Treatment of the cancer cells with ZnO-NPs, Fe-ZnO-NPs, Ag-ZnO-NPs, Pb-ZnO-NPs, and Co-ZnO-NPs resulted in a significant increase in the activity of SOD and the levels of H2O2 and NO than those of control, accompanied with a significant decrease in the activity of CAT and GSH-Px. Also, depletion of reduced GSH, total protein and nucleic acids levels was observed. In conclusion, metal-doped ZnO-NPs may induce antiproliferative effect on HepG2 cells under UV-irradiation due to generation of ROS. Therefore, they could be included in modern clinical trials after in vivo more investigations, using photodynamic therapy technique.