Search

Nonalcoholic fatty liver disease (NAFLD) is a major health concern. Endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may be targeted to prevent the progress of nonalcoholic fatty liver disease. Sulforaphane (SFN), a sulfur-containing compound that is abundant in broccoli florets, seeds, and sprouts, has been reported to have beneficial effects on attenuating metabolic diseases. In light of this, the present study was designed to elucidate the mechanisms by which SFN ameliorated ER stress, inflammation, lipid metabolism, and insulin resistance — induced by a high-fat diet and ionizing radiation (IR) in rats. In our study, the rats were randomly divided into five groups: control, HFD, HFD + SFN, HFD + IR, and HFD + IR + SFN groups. After the last administration of SFN, liver and blood samples were taken. As a result, the lipid profile, liver enzymes, glucose, insulin, IL-1β, adipokines (leptin and resistin), and PI3K/AKT protein levels, as well as the mRNA gene expression of ER stress markers (IRE-1, sXBP-1, PERK, ATF4, and CHOP), fatty acid synthase (FAS), peroxisome proliferator–activated receptor-α (PPAR-α). Interestingly, SFN treatment modulated the levels of proinflammatory cytokine including IL-1β, metabolic indices (lipid profile, glucose, insulin, and adipokines), and ER stress markers in HFD and HFD + IR groups. SFN also increases the expression of PPAR-α and AMPK genes in the livers of HFD and HFD + IR groups. Meanwhile, the gene expression of FAS and CHOP was significantly attenuated in the SFN-treated groups. Our results clearly show that SFN inhibits liver toxicity induced by HFD and IR by ameliorating the ER stress events in the liver tissue through the upregulation of AMPK and PPAR-α accompanied by downregulation of FAS and CHOP gene expression.

Nattokinase (NK), a protease enzyme produced by Bacillus subtilis, has various biological effects such as lipid-lowering activity, antihypertensive, antiplatelet/anticoagulant, and neuroprotective effects. Exposure to environmental toxicants such as bisphenol A (BPA) or γ-radiation (IR) causes multi-organ toxicity through several mechanisms such as impairment of oxidative status, signaling pathways, and hepatic and neuronal functions as well as disruption of the inflammatory responses. Therefore, this study is designed to evaluate the ameliorative effect of NK against BPA- or IR-induced liver and brain damage in rats. Serum ammonia level and liver function tests were measured in addition to brain oxidative stress markers, amyloid-beta, tau protein, and neuroinflammatory mediators. Moreover, relative quantification of brain nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) genes, as well as apoptotic markers in brain tissue, was carried out in addition to histopathological examination. The results showed that NK improved liver functions, impaired oxidative status, the cholinergic deficits, and minified the misfolded proteins aggregates. Furthermore, NK alleviated the neuroinflammation via modulating NF-κB/Nrf2/HO-1 pathway and glial cell activation in addition to their antiapoptotic effect. Collectively, the current results revealed the protective effect of NK against hepatic and neurotoxicity derived from BPA or IR.

Improving radiation effect on tumor cells using radiosensitizers is gaining traction for improving chemoradiotherapy. This study aimed to evaluate copper nanoparticles (CuNPs) synthesized using chrysin as radiosensitizer with γ-radiation on biochemical and histopathological approaches in mice bearing Ehrlich solid tumor. CuNPs were characterized with irregular round sharp shape with size range of 21.19–70.79 nm and plasmon absorption at 273 nm. In vitro study on MCF-7 cells detected cytotoxic effect of CuNPs with IC50 of 57.2 ± 3.1 μg. In vivo study was performed on mice transplanted with Ehrlich solid tumor (EC). Mice were injected with CuNPs (0.67 mg/kg body weight) and/or exposed to low dose of gamma radiation (0.5 Gy). EC mice exposed to combined treatment of CuNPs and radiation showed a marked reduction in tumor volume, ALT and CAT, creatinine, calcium, and GSH, along with elevation in MDA, caspase-3 in parallel with inhibition of NF-κB, p38 MAPK, and cyclin D1 gene expression. Comparing histopathological findings of treatment groups ends that combined treatment was of higher efficacy, showing tumor tissue regression and increase in apoptotic cells. In conclusion, CuNPs with a low dose of gamma radiation showed more powerful ability for tumor suppression via promoting oxidative state, stimulating apoptosis, and inhibiting proliferation pathway through p38MAPK/NF-κB and cyclinD1.

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...

Synthesized gallium nanoparticles synthesized by grape seed extract were characterized with spherical shape and size range less than100 nm, possessing the functional groups of the biological material. The purpose of this study is to evaluate gallium nanoparticles synthesized by grape seed extract, as an antitumor agent with low dose of γ-radiation against hepatocellular carcinoma in rats.This work aimed to evaluate the antitumor effect of gallium nanoparticles synthesized (GaNPs) by grape seed extract and the co-binded treatment with low dose of γ-radiation on hepatocellular carcinoma in rats, through evaluating their effect on signaling pathways and tumor markers.Cytotoxic activity of GaNPs synthesized by grape seed extract was estimated by mediated cytotoxicity assay on HepG2 cell line that recorded ICIt can be concluded that the combined treatment with GaNPs synthesized by grape seed extract and low dose γ-radiation may have antineoplastic activity against hepatocarcinogenesis by inhibiting signal pathways extracellular signal-regulated kinase/mitogen-activated protein kinase/c-Jun NH2-terminal kinase and stimulating apoptotic protein.

Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity.In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured.The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats.The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

Background: Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromenes activity varies between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behavior other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and antitumor activity. Methods: In the present study a new chromene derivative (Ch) was studied against HCC induced by diethylnitrosamine (DEN) in rats. Results: The treatment strategy Ch compound is to down regulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently controls other factors such as p53, Cyt C and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN induced HCC in rats. Conclusion: The ability to control the primary initiators of HCC offers the new Ch derivative an antitumor activity and encourages further researches to follow and monitor its effect on the molecular level.

Background: Liver injury due to ionizing radiation exposure either accidental or after radiotherapy treatment, may lead to many alterations in proteins expression related to inflammation or apoptosis. Our study investigated the curative effect of Mangosteen (MGS) extract (fruit rind) against ionizing radiation (IR) induced liver damage. Methods: Hepatotoxicity was induced in Wister rats by exposure to an acute single dose (6 Gy) of IR while MGS was given orally to rats (500 mg/kg bwt) and administered daily for 30 days after irradiation. Results: MGS treatment has significantly attenuated redox imbalance state and toxicity induced by protracted exposure to gamma-rays in liver tissues, which was substantiated by the significant amelioration of liver function tests, MDA contents, antioxidant enzymes (SOD and CAT) activities and NO level. MGS inhibited also the inflammatory markers (TNF-alpha, IL-6 and CRP) and downregulated transcriptional factor NF-Kappa-B/TGF-β1. These alterations were concomitant with an improvement of the Proliferating cell nuclear antigen (PCNA) which is a protein expressed in the nuclei of cells during cell cycle and is important for both DNA synthesis and DNA repair. These results were confirmed by amelioration in histological and ultrastructural examinations. Conclusion: We concluded that MGS could ameliorate via minimizing significantly the amount of oxidative damage, inflammations disturbances and pro-apoptotic alternations induced by IR. MGS may be a promising supplement with protective effects from irradiation-induced injury such as TNF-α/NF-κB/TGF-β1 management.

The present study was designed to evaluate the suspected anticancer activity of Solenostemma argel (200 mg/kg body weight/ day) either alone or combined with cisplatin (0.64 mg/kg body weight/day) for 4 weeks against lung cancer induced by DMBA (20 mg/kg bw) for 8 weeks in male Wistar rats.At the end of experiment, blood and Lung samples were collected to assess biochemical and biophysical markers as well histopathological investigations. Biochemical parameters:, serum Tumor suppressor protein (P53) and (P16), Transforming Growth Factor-beta (TGF-β), interleukin-1beta (IL-1β), interleukin-6 (IL-6), Carcino Embryonic antigen (CEA). Lung induced nitric oxide synthase (i-Nos), cyclin dependent kinase-2 (CDK2). The level of significance between mean values was set at p < 0.05. The results of this study also showed that administration of olenostemma argel to lung carcinoma induced rats demonstrated a significant improvement in biochemical parameters and life span as compared to DMBA control rats. The histopathological examinations of this study revealed damage and degeneration in the lung of DMBA treated rats. Also, lung of Argel and Cisplatin rats showed significant improvement and protection against DMBA harmful effect.

Background 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. Methods Rats exposed to a single dose of IR (6 Gy, as an acute effect) or a fractionated dose of IR (2 Gy/time/3 days, 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. Results 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. Conclusion 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.

Combining chemotherapy with radiotherapy potentiates the outcome of cancer treatment for the more comprehensive attack. In the current study, we continued to assess the therapeutic efficaciousness of the newly synthesized gallium nanoparticles (GaNPs) combined with low level of gamma radiation (IR), on the incidence of diethylnitrosamine (DEN)–induced hepatocellular carcinoma (HCC) in rats. Oral administration of GaNPs (1 mg/Kg b.wt.) 5 times per week for 6 weeks combined with IR to rats treated with DEN (20 mg/Kg b.wt. 5 times per week for 6 weeks) significantly reduced serum levels of alpha-fetoprotein (AFP), aspartate transferase (AST), alanine transferase (ALT), and gamma-glutamyltransferase (GGT). In addition, the immunoblotting results of matrix metalloproteinase-9 (MM-9) showed a marked downregulation of protein expression along with a significant decrease in the hepatic level of transforming growth factor β (TGF-β). Furthermore, GaNPs and/or low dose of radiation significantly elevated the level of caspase-3 gene transcript accompanied with evoked DNA fragmentation in rats treated with DEN. The ameliorative effect of GaNPs and IR well appreciated with the histopathological alteration finding in DEN groups. It can be concluded that the combination of GaNPs and/or IR can serve as a good therapeutic agent for the treatment of HCC, which ought to attract more studies.

The present study was designed to elucidate the protective effect of subsequent pretreatment withFructus Piperis Longi extract in liver and brain tissue of experimental rats exposed to Hepaticencephalopathy induced by intraperitoneal administration of TAA. Plf extract (50 mg/kg) was force-fedto rats every day, 7 days before administration of Thioacetamide. Thioacetamide 200 mg/kg wasintraperitoneally administered to rats twice per week for four weeks. Administration of Plfext wasextended during Thioacetamide. After 4 weeks, animals were sacrificed. Biochemical parameters inserum and homogenized liver and brain were tested. A significant increase in serum transglutaminase,alkaline phosphatase and gamma glutamyl transferase activity and plasma ammonia, a significantdecrease in serum albumin and total protein was recorded in the liver of Thioacetamide-treated rats.Significant increases in liver and brain lipid peroxides associated to significant decreases of liver andbrain reduced glutathione concentration and catalase activities were also recorded. Administration ofPlfext treatment reduced the severity of liver fibrosis and oxidative damage which was substantiated byimprovement of liver function detected by a decrease in serum aspartate amino transaminase, alanineaminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and increase in totalprotein and Albumin. It was concluded that treatment of the ethanolic extract of Fructus Piperis Longienhance Liver and brain parameter and enhanced antioxidant activities of liver and brain.

This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.

5, 7-Dihydroxyflavone (DHF), a natural plant flavonoid, have shown a variety of beneficial effects. Neurotoxic effects of acrylamide (ACR) or gamma irradiation (IR) have been established in humans and animals. The current study was designed to evaluate whether DHF could restrain ACR or IR induced neurotoxicity in rats and to explore the underlying mechanisms. The study was carried out by investigating some biochemical and biophysical parameters as well as histopathological examination. The daily oral administration of ACR (25mg/kg b.wt.) for 21days or exposure to single dose of IR (5Gy) induced brain damage throughout the significant decrease in catecholamine contents and brain derived neurotrophic factor (BDNF) in brain tissue with a concomitant significant decrease in serum activity of creatinine kinase-BB. Moreover, the brain levels of MDA and β-amyloid and activities of acetylcholinesterase and caspase-3 were remarkably augmented in ACR-induced rats. Additionally, the electrical properties of erythrocytes membrane were significantly disturbed. The administration of DHF (50mg/kg b.wt. daily for 21day) to rats exposed to either ACR or IR significantly reversed the alteration in all studied parameters. Histopathological investigation of brain tissues supported the neuroprotective effect of DHF on brain. From the obtained data, it can be concluded that the DHF has neuroprotective effect against ACR or IR induced-neurotoxicity.

Hepatic encephalopathy (HE) is a syndrome resulting from acute or chronic liver failure. This study was designed to evaluate the effect of rutin on thioacetamide (TAA) or γ-radiation-induced HE model. Animals were received with TAA (200mg/kg, i.p.) twice weekly for four weeks or exposed to 6Gy of γ-radiation to induce HE then groups orally treated with rutin (50mg/kg b.wt.) for four weeks. At the end of experiment, blood, liver and brain samples were collected to assess biochemical and biophysical markers as well histopathological investigations. TAA or γ-radiation exposed rats experienced increases in serum activities of ALT, AST, ALP and ammonia level. Also an alteration in relative permeability and conductivity of erythrocytes was observed. Furthermore, cytokines levels and AChE activity were induced whereas the activities of HO-1 and neurotransmitters contents were depleted. TAA or γ-radiation caused distortion of hepatic and brain architecture as shown by histopathological examination. Treatment with rutin resulted in improvement in liver function by the decline in serum AST and ALT activities and reduction in serum ammonia level. In addition, the administration of rutin significantly modulated the alteration in cytokines levels and neurotransmitters content. Histopathological examinations of liver and brain tissues showed that administration of rutin has attenuate TAA or radiation-induced damage and improve tissue architecture. Consequently, rutin has been a powerful hepatoprotective effect to combat hepatic encephalopathy associated hyperammonemia and its consequential damage in liver and brain.