A comparative study on the protective effects of cuminaldehyde, thymoquinone, and gallic acid against carbon tetrachloride-induced pulmonary and renal toxicity in rats by affecting ROS and NF-κB signaling.

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-Ò¡B, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

Seedless black Vitis vinifera polyphenols suppress hepatocellular carcinoma in vitro and in vivo by targeting apoptosis, cancer stem cells, and proliferation.

Hepatocellular carcinoma (HCC) is an aggressive tumor and one of the most challenging cancers to treat. Here, we evaluated the in vitro and in vivo ameliorating impacts of seedless black Vitis vinifera (VV) polyphenols on HCC. Following the preparation of the VV crude extract (VVCE) from seedless VV (pulp and skin), three fractions (VVF1, VVF2, and VVF3) were prepared. The anticancer potencies of the prepared fractions, compared to 5-FU, were assessed against HepG2 and Huh7 cells. In addition, the effects of these fractions on p-dimethylaminoazobenzene-induced HCC in mice were evaluated. The predicted impacts of selected phenolic constituents of VV fractions on the activity of essential HCC-associated enzymes (NADPH oxidase "NADPH-NOX2", histone deacetylase 1 "HDAC1", and sepiapterin reductase "SepR") were analyzed using molecular docking. The results showed that VVCE and its fractions induced apoptosis and collapsed CD133+ stem cells in the studied cancer cell lines with an efficiency greater than 5-FU. VVF1 and VVF2 exhibited the most effective anticancer fractions in vitro; therefore, we evaluated their influences in mice. VVF1 and VVF2 improved liver morphology and function, induced apoptosis, and lowered the fold expression of various crucial genes that regulate cancer stem cells and other vital pathways for HCC progression. For most of the examined parameters, VVF1 and VVF2 had higher potency than 5-FU, and VVF1 showed more efficiency than VVF2. The selected phenolic compounds displayed competitive inhibitory action on NADPH-NOX2, HDAC1, and SepR. In conclusion, these findings declare that VV polyphenolic fractions, particularly VVF1, could be promising safe anti-HCC agents.

The black Vitis vinifera seed oil saponifiable fraction ameliorates hepatocellular carcinoma in vitro and in vivo via modulating apoptosis and ROS/NF-κB signaling.

To date, no total curative therapy for hepatocellular carcinoma (HCC) is available. This study aimed to evaluate the anticancer effect of black Vitis vinifera (VV) seed oil saponifiable (Sap) fraction (BSap) using five different cancer cell lines. The apoptotic and anti-inflammatory impacts of BSap on the cell line with the highest cytotoxic effect were studied. Furthermore, its therapeutic effect on p-dimethylaminoazobenzene (p-DAB)-induced HCC in mice was investigated. The phenolic and vitamin content, as well as the antiradical activities of BSap, were assessed. BSap demonstrated a greater cytotoxic effect on HepG-2 cells (lowest IC50 and highest SI values) than did the other tested cell lines. BSap showed superior anticancer efficacy to 5-FU on all examined cancer cells, particularly HepG-2 cells, by inducing apoptosis and downregulating NF-κB. In HCC-bearing mice, BSap reduced hepatic lipid peroxidation and boosted GSH levels due to its potent antiradical activities and high reducing power. In addition, it had an apoptotic effect by upregulating p53 and BAX and downregulating Bcl-2 fold expression. Moreover, BSap lowered the fold expression of various crucial HCC-related genes: CD133, ALAD1α1, COX-2, ABCG1, AKT1, Gli, Notch1, and HIF1α. Liver function markers and histopathology showed significant improvements in HCC-bearing mice after BSap administration compared to 5-FU. In silico analysis revealed that the most abundant phenolic and fatty acid ingredients of BSap exhibited competitive inhibitory effects on valuable HCC-associated enzymes (NADPH oxidase, histone deacetylase 1, and sepiapterin reductase). Thus, BSap fraction may be a promising treatment of HCC.

The association between body mass index elevation and differentiation in vitamin D receptor gene expression, genetic polymorphism, and oxidative stress in adult Egyptian individuals.

Vitamin D plays a central role in maintaining calcium, phosphorus, and bone homeostasis in close interaction with the parathyroid hormone. Obesity is a significant health problem worldwide, particularly in developed nations. The current study was carried out to investigate the possible relationship between body mass index (BMI) elevation and differentiation in 25-hydroxyvitamin D (VD), vitamin D receptor (VDR) gene expression, and genetic polymorphism besides oxidative stress in adult Egyptian individuals. This was done to explore the mechanisms underlying the suggested role of the VD/VDR complex in the pathogenesis of obesity. A total of 70 subjects (30 obese, 25 overweight, and 15 normal, age: 20-50 years, without other chronic diseases) were selected. The study focused on the determination of VD, VDR gene polymorphism, VDR gene expression, alkaline phosphatase, calcium, phosphorus, glucose, lipid profile, oxidative stress including, oxidant (malondialdehyde), and anti-oxidants (reduced glutathione and superoxide dismutase). The results showed that elevation in BMI led to the percentage of the Ff 'allele' becoming predominant, while the percentage of the FF 'allele' was in the normal BMI range. Also, BMI elevation caused significant reductions in VD and VDR expression, with significant elevations in alkaline phosphatase and the levels of calcium and phosphate in serum. Also, oxidative stress increases with increasing BMI. Elevation in BMI causes a reduction in VD concentration and VDR gene expression levels. Also, the percentage of heterozygous mutant genotype Ff 'allele' is predominantly in the obese human, in contrast to normal subjects, where the percentage of homozygous wild genotype FF 'allele' is predominant. In general, the genetic expression and polymorphism of VD and VDR can be used as a genetic marker for predisposition, diagnosis, prognosis, and progression of obesity.

A new approach for the treatment of bleomycin-induced rat pulmonary injury by combined protein fraction of major royal jelly protein 2 and its isoform X1.

Nowadays, royal jelly (RJ) has gained great interest as a functional food due to its valuable pharmacological effects. We investigated the therapeutic potency of combined protein fraction (PF50) of major RJ protein 2 and its isoform X1 on bleomycin (Bleo)-induced pulmonary injury in rats. Our study examined the impact of PF50 on pulmonary oxidative and inflammatory stress as well as smooth muscle alpha-actin (α-SMA). In addition, the predicted impacts of this PF on the activity of matrix metalloproteinase (MMP)- 8 and 15-prostaglandin dehydrogenase (15-PGDH) and the E-type prostanoid 2 (EP2) and IL-13 α2 subunit (IL13α2R) receptors, were evaluated using molecular docking. The results showed that PF50 reduced pulmonary inflammatory cells and their secreted pro-inflammatory mediators, including NF-κB, IKK, IL-4, IL-6, and NO. Additionally, the levels of IgE and mucin were diminished after treatment with PF50. Moreover, PF50 treatment improved pulmonary oxidative stress indices such as lipid peroxidation, GSH, SOD, and GPX. The histopathological findings, chest conventional X-ray, and immunohistochemistry of α-SMA confirmed the ameliorating effect of PF50. The docking outcomes reported the probable competitive inhibitory influence of PF50 on MMP-8 and a postulated blocking effect on EP2 and IL13α2R. Thus, PF50 could be a novel approach for treating pulmonary injuries.

Anticancer role of mango (Mangifera indica L.) peel and seed kernel extracts against 7,12- dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rats.

Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague-Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-ß estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.

Targeting apoptosis in MCF-7 and Ehrlich ascites carcinoma cells by saponifiable fractions from green and black Vitis vinifera seed oil.

Grape seed (GS) oil is one of the potential functional foods. For the first time, we evaluated the therapeutic effects of GS oil saponifiable (Sap)-fraction from black (BSap) and green (GSap) grapes on MCF-7 cells and Ehrlich ascites carcinoma (EAC) in mice. The fatty acid composition of BSap and GSap was determined using gas chromatography-mass spectrometry analysis. Approximately twelve distinct fatty acids were detected in BSap and eleven in GSap. BSap showed a greater cytotoxic effect on MCF-7 cells than GSap did by inducing apoptosis and reducing inflammation, while both grape fractions had superior potency to 5-FU. Furthermore, BSap massively boosted apoptosis and lowered redox potential (Eh) and CD44+ cells in EAC cells of EAC-bearing mice more than GSap, and both fractions were more efficient than 5-FU. Blood tests and liver histopathology revealed significant improvement in EAC-induced pathological alterations with these fractions. The in silico analysis implied the competitive inhibitory impacts of the most abundant fatty acid composites in BSap and GSap on cancer-metastasis-associated proteases (cathepsin B and MMP9). Also, this analysis predicted that the apoptotic action of these Sap fractions is independent of the 5'AMP-activated protein kinase. Therefore, grape Sap-fraction, especially BSap, may be a useful agent for cancer prevention.

Regulation of the NF-κB signaling pathway and IL-13 in asthmatic rats by aerosol inhalation of the combined active constituents of Punica granatum juice and peel.

Bronchial asthma is a chronic inflammatory airway illness. For the first time, we evaluated the proposed anti-asthmatic protective and therapeutic potency of inhaling Punica granatum juice (PJE) and peel (PPE) extract mixture (PM). Rats were challenged with ovalbumin (OVA) for 23 days and aerosolized with PM before each OVA challenge (protected group) or following the final OVA challenge for 3 days (therapeutic group). Considerable concentrations of phenolics were detected in PJE and PPE. Therefore, PM demonstrated synergistic scavenging abilities of NO and DPPH radicals. It also showed synergistic anti-inflammatory activities against lipopolysaccharide (LPS)-induced inflammation in the white blood cells by lowering the gene expression of CXCR1, CXCR2, IL-6, and IL-8. In addition, PM increased IL-10 gene expression while decreasing NO and TNF-α levels in LPS-exposed cells. Regarding the rats that were protected with PM, they exerted pulmonary pro-oxidant effects but prevented the OVA-induced upregulation of NF-κB, IKK, TNF-α, COX-2, iNOS, IL-13, and COL1A1, as well as MUC5AC and mucin over-secretion. While PM in the therapeutic group improved reactive oxygen species levels and normalized most of the investigated inflammatory and fibrotic mediators and mucin formation, but slightly improved the antioxidant indices. In addition, OVA-induced morphological alterations were massively improved after PM inhalation for short or long periods. Thus, PM inhalation prevented and treated OVA-induced pulmonary inflammation and fibrosis, while the inhalation period between 3 and 23 days needs to be optimized to acquire a better impact on the antioxidant indices.

Inhibition of oxidative stress, IL-13, and WNT/ß-catenin in ovalbumin-sensitized rats by a novel organogel of Punica granatum seed oil saponifiable fraction.

Bronchial asthma is a chronic inflammatory disease marked by inflammation, oxidative stress, and structural remodeling. Here, we prepared two pomegranate fractions from the seed oil, saponifiable (Sap) and unsaponifiable (UnSap). Two organogels (Orgs) were also formulated with the Sap (Org1) or the UnSap (Org2) fraction and beeswax (BW). All preparations were evaluated in vitro for their antioxidant and anti-inflammatory impacts. The transdermal delivery of the most efficient one was evaluated against ovalbumin (OV)-induced bronchial asthma in rats compared to dexamethasone (DEX). The results showed that the prepared pomegranate fractions and BW had considerable amounts of phenolics (flavonoids and tannins) and triterpenoids. Org1 was shown to be the most effective antioxidant and anti-inflammatory fraction with synergistic activities (combination index, 1), as well as having protective and therapeutic influences on OV-sensitized rats. Org1 inhibited the multiple OV-induced signaling pathways, comprising ROS, WNT/ß-catenin, and AKT, with an efficiency superior to DEX. Subsequently, the pro-inflammatory (COX-2, NO, and IL-13), and pro-fibrotic (COL1A1) mediators, oxidative stress, and mucin secretion, were all down-regulated. These outcomes were verified by the histopathological results of lung tissue. Collectively, these outcomes suggest that the transdermal delivery of Org1 to OV-sensitized rats shows promise in the protection and treatment of the pathological hallmarks of asthma.

Therapeutic effect of dithiophenolato chitosan nanocomposites against carbon tetrachloride-induced hepatotoxicity in rats.

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD50) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl4) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl-2 value, with decreases in caspase-8, Bax, and Bax/Bcl-2 ratio. DPT-CSNPs treatment gave preferable results than those treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than cisplatin treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion, DTP and DTP-CSNPs have antiapoptotic and anti-oxidative stress toward hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPs.

Cellulose Acetate Nanofibers: Incorporating Hydroxyapatite (HA), HA/Berberine or HA/Moghat Composites, as Scaffolds to Enhance In Vitro Osteoporotic Bone Regeneration.

The specific objective of this study was to stabilize a simple valid method to prepare pure nanorod hydroxyapatite (HA) mixed with berberine chloride (BER) and Moghat water extract (ME) as composites for incorporation into cellulose acetate (CA) nanofibers to be used as novel bone scaffolds and to determine their efficacy in bone regeneration process In Vitro. Preparation of HA/BER and HA/ME composites were performed by mixing powders using the ball-milling machine. The HA, HA/BER, and HA/ME composites at a concentration of 6.25, 12.5, 25, 50, 100, and 200 mg were mixed with CA solution (13%), then the fiber was formed using electrospinning technique. The properties of the obtained CA fibers were investigated (SEM, TEM, EDX, FTIR, TGA, water uptake, porosity, and mechanical tests). The efficacy of HA and HA composites loaded into CA nanofiber on osteoblast and osteoclast differentiation were measured by tacking ALP, osteocalcin, TRAcP, calcium, and total protein concentration. Moreover, their effects on cell differentiation (CD90 and PARP- É£) and death markers (GSK3b, MAPK, Wnt-5 and ß-catenin) were evaluated by using ELISA and qPCR. The obtained TEM results indicated that the continuous CA and CA/HA composites electrospun fibers have ultrafine fiber diameters of about 200 nm and uniform distribution of discrete n-HA clusters throughout. In addition, hydrocortisone (HCT) was found to increase the formation of adipocytes and osteoclastic markers CD90 and p38-MAPK which indicated the bone lose process take placed. Treatment with CA loaded with HA, HA/BER or HA/ME decreased CD90, Wnt-5, PARP- É£, GSK3b and p38-MAPK associated elevation of osteogenic markers: ALP and osteocalcin. Moreover, HCT overexpressed RANKL and down expressed Osterix gene. Treatment with CA/HA/BER or CA/HA/ME downregulated RANKL and upregulated Osterix associated with a reduction in RANKL/OPG ratio, at p < 0.05. In conclusion, novel CA composite nanofibers (CA/HA/BER and CA/HA/ME) reversed the HCT adverse effect on osteoblast cell death through canonical and non-canonical pathways regulated by Wnt/ß-catenin and Wnt/Ca(2+) pathways. Furthermore, our data confirmed that the novel scaffolds create a crosstalk between RUNX-2, RANKL, p38-MAPK, and Wnt signals which positively impact bone regeneration process. Treatment with CA/HA/BER is better compared to the treatment with CA/HA/ME. Nevertheless, both are considered as alternative biomaterial scaffolds with a potential for biomedical applications in the field of bone tissue engineering.

The antioxidant and anti-inflammatory effects of Carica Papaya Linn. seeds extract on CCl4-induced liver injury in male rats.

BACKGROUND: Oxidative stress (OS) and inflammation are the central pathogenic events in liver diseases. In this study, the protective and therapeutic role of Carica Papaya Linn. seeds extract (SE) was evaluated against the hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. METHODS: The air-dried papaya seeds were powdered and extracted with distilled water. The phytochemical ingredients, minerals, and antioxidant potentials were studied. For determination of the biological role of SE against hepatotoxicity induced by CCl4, five groups of adult male Sprague-Dawley rats were prepared (8 rats per each): C: control; SE: rats were administered with SE alone; CCl4: rats were injected subcutaneously with CCl4; SE-CCl4 group: rats were administered with SE orally for 2 weeks before and 8 weeks during CCl4 injection; SE-CCl4-SE group: Rats were administered with SE and CCl4 as mentioned in SE-CCl4 group with a prolonged administration with SE for 4 weeks after the stopping of CCl4 injection. Then, the markers of OS [lipid peroxidation (LP) and antioxidant parameters; glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx)], inflammation [nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6], fibrosis [transforming growth factor (TGF)-ß], apoptosis [tumor suppressor gene (p53)], liver and kidney functions beside liver histopathology were determined. RESULTS: The phytochemical analyses revealed that SE contains different concentrations of phenolics, flavonoids, terpenoids, and minerals so it has potent antioxidant activities. Therefore, the treatment with SE pre, during, and/or after CCl4 administration attenuated the OS induced by CCl4 where the LP was reduced, but the antioxidants (GSH, SOD, GST, and GPx) were increased. Additionally, these treatments reduced the inflammation, fibrosis, and apoptosis induced by CCl4, since the levels of NF-κB, TNF-α, IL-6, TGF-ß, and p53 were declined. Accordingly, liver and kidney functions were improved. These results were confirmed by the histopathological results. CONCLUSIONS: SE has protective and treatment roles against hepatotoxicity caused by CCl4 administration through the reduction of OS, inflammation, fibrosis, and apoptosis induced by CCl4 and its metabolites in the liver tissues. Administration of SE for healthy rats for 12 weeks had no adverse effects. Thus, SE can be utilized in pharmacological tools as anti-hepatotoxicity.

Synthesized Nanorods Hydroxyapatite by Microwave-Assisted Technology for In Vitro Osteoporotic Bone Regeneration through Wnt/ß-Catenin Pathway.

This research presents an optimal and inexpensive, without any additives, method for the synthesis and sintering of hydroxyapatite (HA) by microwave-assisted technology (MAT) furnace. The target sintering temperature of the furnace (1100 ℃) was held for one and two hours for conventional sintering. With regard to the microwave hybrid sintering, it was held at 100%MW for 20 and 30 min. FTIR, XRD, TGA, SEM/EDS, and TEM were assessed to determine HA phase composition, and structural as well as thermal decomposition behavior. The in vitro effects of sintered HA discs on cultured aged mice-isolated osteoblast cells and hydrocortisone-induced osteoclast cells were assessed by measuring ALP, osteocalcin, TRAP, calcium, and Alizarin red S staining. Moreover, their effects on cell differentiation (CD90 and CD 105 and PARR- É£) and death markers (GSK3b, MAPK, and ß-catenin) were evaluated. The results demonstrate the production of ≈35 nm crystal-sized pure hydroxyapatite nanorod-like particles with a high degree of crystallinity and no impurities as required for biomedical application. HA increased osteogenesis (ALP, osteocalcin, and calcium) markers and decreased cell resorption markers. In addition, HA nanorods reversed the effect of cortisone on cell differentiation and death markers. In conclusion, microwave hybrid sintered HA is a potential nanomaterial for osteoporotic bone regeneration as HA reversed the cortisone adverse effect on osteoblast cell death through canonical and non-canonical pathways.

A Titanium (IV)-Dithiophenolate Complex and Its Chitosan Nanocomposite: Their Roles towards Rat Liver Injuries In Vivo and against Human Liver Cancer Cell Lines.

Titanium (IV)-dithiophenolate complex chitosan nanocomposites (DBT-CSNPs) are featured by their antibacterial activities, cytotoxicity, and capacity to bind with DNA helixes. In this study, their therapeutic effects against rat liver damage induced by carbon tetrachloride (CCl4) and their anti-proliferative activity against human liver cancer (HepG2) cell lines were determined. Results of treatment were compared with cisplatin treatment. Markers of apoptosis, oxidative stress, liver functions, and liver histopathology were determined. The results showed that DBT-CSNPs and DBT treatments abolished liver damage induced by CCl4 and improved liver architecture and functions. DNA fragmentation, Bax, and caspase-8 were reduced, but Bcl-2 and the Bcl-2/Bax ratios were increased. However, there was a non-significant change in the oxidative stress markers. DBT-CSNPs and DBT inhibited the proliferation of HepG2 cells by arresting cells in the G2/M phase and inducing cell death. DBT-CSNPs were more efficient than DBT. Low doses of DBT and DBT-CSNPs applied to healthy rats for 14 days had no adverse effect. DBT and DBT-CSNP treatment gave preferable results than the treatment with cisplatin. In conclusion, DBT-CSNPs and DBT have anti-apoptotic activities against liver injuries and have anti-neoplastic impacts. DBT-CSNPs are more efficient. Both compounds can be used in pharmacological fields.

Synergistic protective effect of Beta vulgaris with meso-2,3-dimercaptosuccinic acid against lead-induced neurotoxicity in male rats.

Lead (Pb) toxicity is one of the most prevalent causes of human neurotoxicity. The available chelator drugs used now have many adverse effects. So, in this study, the protective role of Beta vulgaris juice (BVJ) on rat neurotoxicity induced by Pb was evaluated and the results were compared with the results of dimercaptosuccinic acid (DMSA, as used drug). Additionally, the synergistic effect of BVJ and DMSA against Pb-induced neurotoxicity was assessed. The study focused on the determination of the antioxidant, anti-inflammatory, and neurological potential of BVJ (alone, and with DMSA) towards lead-induced neurotoxicity. Also, the characterization of BVJ was studied. The results showed that BVJ contains considerable quantities of polyphenols, triterpenoids, and betalains which play an important role as antioxidants and anti-inflammatory. BVJ exhibited a protective effect against neurotoxicity via the reduction of Pb levels in blood and brain. Moreover, BVJ decreased the oxidative stress, inflammation, and cell death induced by Pb. Also, BVJ regulated the activities of acetylcholine esterase and monoamine oxidase-A which changed by Pb toxicity. BVJ and DMSA combination displayed a synergistic antineurotoxic effect (combination index ˂ 1). These results were in harmony with brain histopathology. Conclusion: BVJ has a powerful efficacy in the protection from brain toxicity via diminishing Pb in the brain and blood circulation, resulting in the prevention of the oxidative and inflammatory stress. Treatment with BVJ in combination with DMSA revealed a synergistic effect in the reduction of neurotoxicity induced by Pb. Also, the antioxidant and anti-inflammatory effects of the BVJ lead to the improvement of DMSA therapy.

The synergistic hepatoprotective potential of Beta vulgaris juice and 2,3- dimercaptosuccinic acid in lead-intoxicated rats via improving the hepatic oxidative and inflammatory stress.

BACKGROUND: Lead (Pb) is observed in all areas of the environment, mainly derived from human operations such as mining, processing, and burning fossil fuels. Pb toxicity is one of the most prevalent causes of human hepatotoxicity. The available chelator drugs used now have many adverse effects and therefore the world is looking for natural and secure alternatives. METHODS: Here, we evaluated the hepatoprotective role of the oral administration (1 g/kg b.w.) of the lyophilized Beta vulgaris juice (BVJ) against Pb-induced rat hepatotoxicity. We also examined the possible synergistic hepatoprotective impact of the combination between BVJ and 2,3- dimercaptosuccinic acid (DMSA, the currently approved drug for Pb-toxicity). The evaluation depends on the ability of BVJ, DMSA, or their combination (BVJ-DMSA) to reduce serum and hepatic Pb level and to avoid oxidative stress and inflammation caused by Pb. The level of lipid peroxidation, reduced glutathione (GSH), total antioxidant capacity, and the activity of the antioxidant enzymes were quantified. In addition, the level of interleukin (IL)-6, nitric oxide (NO), DNA fragmentation, and liver histology were studied. RESULTS: The results showed that BVJ contained considerable amounts of betalains, vitamin C, and various types of phenolic compounds. Therefore, BVJ displayed a significant (p < 0.05) preventive influence on the elevation of Pb levels in blood and liver as well as the hepatic DNA fragmentation. In addition, it significantly (p < 0.05) improved most of the studied antioxidant and inflammatory markers in the Pb-intoxicated rats. However, the combined extract (BVJ-DMSA) revealed synergistic (combination index < 1) activities in most of the tested parameters. The histopathological results verified the biochemical findings of this research. CONCLUSION: BVJ has a potent efficiency in the protection from Pb-induced hepatotoxicity through the reduction of its accumulation in blood and liver and the prevention of the oxidative stress and inflammation induced by Pb. Additionally, the treatment of hepatotoxicity with BVJ and DMSA in combination showed a synergistic effect and reduced the adverse effects induced by DMSA. Thus, BVJ can be a promising hepatoprotective extract against lead toxicity and its combination with DMSA potentiates this effect.

Protective role of hesperidin against γ-radiation-induced oxidative stress and apoptosis in rat testis.

BACKGROUND: Gamma (γ) ray, an electromagnetic radiation, is occasionally accompanying the emission of an alpha or beta particle. Exposure to such radiation can cause cellular changes such as mutations, chromosome aberration and cellular damage which depend upon the total amount of energy, duration of exposure and the dose. Ionizing radiation can impair spermatogenesis and can cause mutations in germ cells. In general, type B spermatogonia are sensitive to this type of radiation. The current study was carried out to evaluate the protective role of hesperidin (H), as a polyphenolic compound, on rat testis injury induced by γ-radiation. METHODS: Rats were divided into groups including C group (control rats), R (irradiated) group (rats irradiated with γ-radiation), Vehicle (V) group (rats administered with dimethylsulfoxide "DMSO"), H group (rats administered with H only), HR and RH groups (rats treated with H before and after exposure to γ-radiation, respectively). Malondialdehyde (MDA: the end product of lipid peroxidation "LPO") and xanthine oxidase (XO: it generates reactive oxygen species "ROS") in testes homogenate as well as nitric oxide (NO: as ROS) in mitochondrial matrix were determined. The apoptotic markers including DNA-fragmentation (DNAF) in testes homogenate and calcium ions (Ca2+) in mitochondrial matrix were determined. Superoxide dismutase (SOD) and catalase (CAT) activities in testes homogenate, while reduced glutathione "GSH" in nuclear matrix were determined. Also histopathological examination for testes tissues through electron microscope was studied. RESULTS: Exposure of rats to γ-radiation (R group) increased the levels of MDA, NO, DNAF, Ca2+ and XO activity, while it decreased GSH level, SOD and CAT activities as compared to the C groups; γ-radiation increased oxidative stress (OS), LPO, apoptosis and induced testes injuries. These results are in agreement with the histopathological examination. In contrast, treatment with H before or after exposure to γ-radiation (HR and RH groups, respectively) decreased the levels of MDA, NO, DNAF and Ca2+ but increased GSH level and the activities of SOD, CAT and XO as compared to R group and this indicates that H decreased OS, LPO and apoptosis. Also, the histopathological results showed that H improved testis architecture and this is related to the antioxidant and anti-apoptotic activities of H contents. Protection is more effective when H is given before rather than after exposure. Finally, administration of H to healthy rats for a short period had no adverse affect on testes cells. CONCLUSION: Hesperidin showed antioxidant and anti-apoptotic activities. It has a protective role against OS, injury and apoptosis induced by γ-radiation in testes. Protection is more effective when H is given before rather than after exposure.Graphical Abstract.

Distribution of Glutathione S-Transferase Omega Gene Polymorphism with Different Stages of HBV Infection Including Hepatocellular Carcinoma in the Egyptian Population.

BACKGROUND: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV. MATERIALS AND METHODS: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests. RESULTS: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees. CONCLUSIONS: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

Raw agro-industrial orange peel waste as a low cost effective inducer for alkaline polygalacturonase production from Bacillus licheniformis SHG10.

The current study underlines biotechnological valorization of the accumulated and the non-efficiently utilized agro-industrial orange peel waste to produce polygalacturonase (PGase), an industrially important enzyme with augmented demands in enzymes markets, from Bacillus licheniformis SHG10. Sequential statistical optimization of PGase production was performed through one variable at a time (OVAT) approach, Plackett-Burman (PB) and response surface methodology (RSM). The impact of introduction of six raw agro-industrial wastes (orange, lemon, banana, pomegranate, artichoke peel wastes and wheat bran) and other synthetic carbon sources separately into the fermentation broth on PGase productivity was studied through OVAT approach. Orange peel waste as sole raw carbon source in basal medium proved to be the best PGase inducer. It promoted PGase productivity with relative specific activity of 166% comparable with the effect imposed by synthetic citrus pectin as a reference inducer. Three key determinants (orange peel waste, pH of the production medium and incubation temperature) had RSM optimal levels of 1.76% (w/v), 8.0 and 37.8°C, respectively along with maximal PGase level (2.69 µg galacturonic acid. min(-1). mg(-1)) within 48 hrs. Moreover, SHG10 PGase exhibited activity over a wide range of pH (3-11) and an optimal activity at 50°C. Data greatly encourage pilot scale PGase production from B. licheniformis SHG10.

Effect of Punica granatum (pomegranate) juice extract on healthy liver and hepatotoxicity induced by diethylnitrosamine and phenobarbital in male rats.

The effect of pomegranate juice (PJ) on hepatic antioxidant enzyme activities, lipid peroxidation, DNA fragmentation (DNAF), and caspase-3 activity in rats both treated and not treated with diethylnitrosamine (DEN) and phenobarbital (PB) was studied. Administration of rats with DEN and PB caused an elevation in the levels of malondialde-hyde (MDA), DNAF, and activities of glutathione reductase (GSR) and caspase-3, while the activities of superoxide dismutase, glutathione S-transferase, total glutathione peroxidase (t-GPx), and glutathione (GSH) level were decreased in hepatocytes compared to the control. Treatment of rats with PJ pre, during, and post DEN and PB administration improved liver function and decreased the levels of MDA, DNAF, t-GPx, GSR, and caspase-3 activities, but the GSH level did not change compared to the D-P group. This indicates that PJ reduced the oxidative stress and apoptosis induced by DEN and PB. Administration of healthy rats with PJ only for a long period induced oxidative stress and apoptosis for hepatocytes.