Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain cau... more Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits. Western immunoblotting, spectrophotometric, and histological methods were used in this study. Tramadol (1.5 mg/kg body weight) was administered orally to male rabbits for up to three months (three times/week), and after pretreatment of rabbits with garlic (800 mg/kg) and/or selenium (1 mg/kg body weight) by 2 h. The present study showed that motilities, semen volumes, morphologies, sperm counts, testosterone, and estrogen levels were significantly decreased after 4, 8, and 12 weeks of tramadol treatment. In addition, the protein expressions of CYP 21A2, CYP 19, and 11A1 were down-regulated in the testes of the tramadol-treated rabbits. On the other hand, pretreatment of rabbits with garlic, selenium, and/or garlic-selenium for 2 h before administration of tramadol restored the downregulated CYP 21A2 and 11A1 to their normal levels after 12 weeks of tramadol treatment. Activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the testes of tramadol-treated rabbits. On the other hand, free radical levels were significantly increased in the testes of tramadoltreated rabbits for 12 weeks. Interestingly, such changes in the activities of antioxidant enzymes as well as free radical levels caused by tramadol were restored to their normal levels in the rabbits pretreated with either selenium, garlic, and/or their combination. Histopathological investigations showed that tramadol caused substantial vacuolization with the presence of damaged immature spermatozoid in the testes. However, selenium and garlic treatments showed an increase in healthy sperm production with normal mitotic and meiotic divisions. The present study illustrated for the first time the mechanisms of low steroid hormone levels in the testes of tramadol-treated rabbits which could be due to the downregulation of CYPs proteins, induction of oxidative stress, and inhibition of antioxidant enzyme activities. In addition, the present data showed that such toxic effects of tramadol were attenuated and restored to their normal levels after pretreatment of rabbits with garlic, selenium, and/or their combination. This finding may pave the way for a new approach to reducing the toxicity of tramadol.
The influence of Schistosoma mansoni infection on the capacity of the carcinogen-metabolizing enz... more The influence of Schistosoma mansoni infection on the capacity of the carcinogen-metabolizing enzymes was investigated prior to and after treatment of the infected male mice with praziquantel, an anti-schistosomal agent. The drug was administered in a daily dose of 60 mg/kg body weight for three days before decapitation at various infection intervals. After 20 and 30 days post-infection the hepatic content of cytochrome P-450 and cytochrome b-5 and the activity of aryl hydrocarbon hydroxylase were markedly increased. However, the constitutive levels of the above mentioned enzymes were significantly decreased at 45, 60 and 75 days post-infection. Treatment of the infected mice with praziquantel for three days, however, recovered the changes in these activities at each individual time point. Praziquantel showed no effect on either of the studied enzymes when administered alone except for that of NADPH-cytochrome C reductase activity which exhibited significant increase. The activity of NADPH-cytochrome C reductase gave inconsistent results after treatment of the infected animals with praziquantel. It is concluded that praziquantel can be considered as a safe and useful drug for the chemotherapy of schistosomiasis and it possessed a recovery for the activities of the drug-metabolizing enzyme.
Recently, different microbial ghosts (BGs) were prepared using a strategy based on the critical c... more Recently, different microbial ghosts (BGs) were prepared using a strategy based on the critical chemical concentrations. In the original protocol, it was given the name "Sponge Like" (SL) protocol. The protocol was reduced to be more reliable and given the name "Sponge Like Reduced Protocol" (SLRP). In this study, using SLRP we succeeded to prepare Klebsiella pneumoniae (KPGs) with correct 3D structure and surface antigens. The study has included oral, S/C, inhalation, I/P and I/M vaccination with KPGs and controlled with challenge test. Results of both the SLRP and the animal experiments prove that we have KPGs able to immunize rats subjected to different routes of administration against viable K. pneumoniae. The evaluation of the immune response include humoral and cellular immune responses, IFN-γ production, phagocytic activity, NBT reduction activity, serum agglutination titer and the bacterial load in the various tissues, was performed in BG-vaccinated animals subsequently challenged with K. pneumoniae. The results were compared with animals that were not immunized with the KPGs. KPGs not only are able to promote the generation of high titer antibodies and IFN-γ production but also are able to stimulate a significant increase in phagocytic activity, NBT reduction, a marked decrease in the bacterial load in the various tissues, indicated that the vaccine was able to induce clearance of intracellular K. pneumoniae. The protective effects of BG vaccination in rats against virulent K. pneumoniae were a result of the induction of a more effective immune response in vaccinated animals than that observed with the non-vaccinated animals. These findings demonstrate the potential of K. pneumoniae ghosts to be used as effective vaccines.
Journal of Infection and Public Health, Nov 1, 2019
BACKGROUND Human infection by Acinetobacter baumannii has been increased due to its resistance ag... more BACKGROUND Human infection by Acinetobacter baumannii has been increased due to its resistance against most of the antibiotics. Therefore, the present study aimed to design a candidate vaccine against A. baumannii infection. METHODS The protein and DNA contents of A. baumannii Ali190 were extracted using different critical concentrations of hydrogen peroxide, sodium hydroxide and sodium carbonate leading to the ghost of A. baumannii Ali190. Transmission and scanning electron microscope showed that it retained the 3D structure of its cell membrane. The ghost injected to rats via different routes of administrations including oral, subcutaneous, intramuscular, intraperitoneal, subcutaneous with adjuvant, and intramuscular with adjuvant. RESULTS β-Lactamase OXA-51 gene, is a predominant gene in all Acinetobacter strains, the gene was partially sequenced. The DNA sequence of OXA-51 gene showed 98% homology with A. baumannii isolate 6077/12 and also showed less homology percentage with other strains of Acinetobacter. A new strain of Acinetobacter has been deposited in Gene Bank under accession number MG062776. All routes of ghost administration showed full protection against live bacteria except oral administration showed 67% protection. On the other hand, all non-vaccinated rats did not survive after infection with live bacteria. SDS-gel electrophoresis of protein patterns of both A. baumannii and its ghost showed common protein bands with molecular weights 70, 60, and 23 kDa which were detected using western immunoblotting after raising the primary antibodies against A. baumannii ghost. The levels of INF-γ were significantly increased in all vaccinated groups, particularly in subcutaneous and subcutaneous with adjuvant compared to the control group. CONCLUSION With the exception of oral administration, all vaccinated rats via different routes of ABG administration showed full protection (100%) against live A. baumannii. However, 100% mortality rate was observed in non-vaccinated rats. Therefore, ABG could be useful as a candidate vaccine against A. baumannii infection.
Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liv... more Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liver injury. The combination of amoxicillin with clavulanic acid is commonly cited in such cases. Accordingly, the present study investigated the potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was hydrodistilled from the aerial parts of Salvia officinalis L. and its compositional analysis was characterized by Gas chromatography-Mass spectroscopy. Rats were treated singly or concomitantly with Co-amoxiclav and sage essential oil for a period of seven days. The major components of sage oil as identified by GC-MS were 1,8-cineole, β-pinene, camphor, β-caryophyllene, α-pinene and α-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5% respectively. The in vivo exposure of rats to Co-amoxiclav resulted in hepatotoxicity biochemically evidenced by the significant elevation of serum AST...
Although, there are several breakthroughs in the treatment of breast cancer on the past few decad... more Although, there are several breakthroughs in the treatment of breast cancer on the past few decades, high incidence of relapse and progression after conventional therapies is deeply concerning, indicating a great need for developing new therapeutics for breast cancer. In the present study, the anti-cancer effects of combinational therapy of Letrozole (Aromatase inhibitor) or Olaparib (PARP inhibitor) with Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), were examined on well differentiated ER-positive and poorly differentiated triple negative breast cancer cell lines, T-47D and MDA-MB-231, respectively. In addition, the effect of combined treatment was also examined by detecting cell survival, cell cycle analysis, and alterations in signaling pathway that play a role in breast cancer progression such as β -catenin, STAT3, cyclin D1, Bax, c-PARP, wild and Mutant p53. In addition the effect of combined treatments were examined on gene expression levels of Cytochromes; CYP1A1, ...
Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to ... more Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. aeruginosa ghosts (PAGs) were prepared to maintain surface antigens and immunogenicity. This is the first study, to our knowledge, on the production of chemically induced well-structured bacterial ghosts for PA using concentrations of different chemicals. The research was carried out using diabetic rats who were orally immunized at two-week intervals with three doses of PAGs. Rats were subsequently challenged either by the oral route or by the model of ulcer infection with PA. In challenged rats, in addition to other immunological parameters, organ bioburden and wound healing were determined, respectively. Examination of the scanning and transmission electron microscope (EM) proved that PAG...
Schistosomiasis ranks as one of the most important health prob-lems in developing countries with ... more Schistosomiasis ranks as one of the most important health prob-lems in developing countries with an estimated 200 millioninfected people in 72 different countries.In Egypt,bilharzialinfection is the most frequently found endemic parasitic disease.
Liver cancer is listed among the most common causes o f cancer-related death. Nowadays the clinic... more Liver cancer is listed among the most common causes o f cancer-related death. Nowadays the clinical diagnosis of early-stage hepatocellular carcinoma (HCC) has improved significantly; nevertheless, HCC prognosis is still highly poor. Therefore, new effective and well-designed therapeutic strategies are urgently recommended. Ruthenium complexes represent a new promising family of metal-based anticancer complexes that exhibit reduced toxicity compared to platinum (II) complexes c urrently used clinically. These complexes show a novel mechanism of action with different spectrum of activity compared to platinum-based drugs. The present study was performed to investigate the effect of new formulated Rhuthenium complex {Bis (quinolin-8-olato) bis (triphenylphosphine) Ruthenium(II)} (Ru(quin)2) with or without sorafenib; the gold standard treatment for advanced HCC, as a combined treatment on different molecular signaling pathway such as ERK1/2, Stat3, AKT/m- TOR and Wnt/β-catenin that are...
Journal of Musculoskeletal Surgery and Research, 2019
Osteoporosis is well recognized in children as a consequence of several factors. Therefore, the p... more Osteoporosis is well recognized in children as a consequence of several factors. Therefore, the present review sheds light on the role of diabetes mellitus (DM), malabsorption, glucocorticoids, nutrition, free radicals, and oxidative stress in the induction of osteoporosis. It may also provide valuable information regarding the early detection of osteoporosis to improve not only the bone health of schoolchildren but also their general quality of life. Measurement of bone mineral density (BMD) does not capture all the risk factors of bone fractures and/or osteoporosis. Therefore, bone resorption and formation markers such as osteoprotegerin; prolidase; osteocalcin; bone alkaline phosphatase and Vitamin D; parathyroid hormones; and macroelements such as calcium, phosphorus, and magnesium should be measured beside BMD in the plasma of school-aged children. Moreover, endocrine abnormalities, high levels of free radicals, and induction of oxidative stress showed an adverse effect on the skeleton and cause osteoporosis. It has been found that there is a strong correlation between osteoporosis and DM, malnutrition, and glucocorticoids in both pediatric and adult patients. Inhibition of antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, was found to increase the production of reactive oxygen species by osteoclasts. Therefore, oxidative stress and other factors are important mediators of bone loss and also osteoporosis. Furthermore, antioxidants should be provided to maintain bone integrity because a deficiency of antioxidant vitamins has been found in the osteoporotic children.
N‐nitrosamines are widely spread environmental pollutants of well‐known toxicity and carcinogenic... more N‐nitrosamines are widely spread environmental pollutants of well‐known toxicity and carcinogenicity in various animal species. These compounds are metabolically activated by cytochrome P450 system predominantly in the liver and in other tissues into more active metabolites leading to generation of both alkylating agents that alkylate DNA and reactive oxygen species. In the current study, we investigated the influence of four types of N‐nitrosamines that are commonly present in the environment [methyethylnitrosamine, (MEN), diethylnitrosamine (DEN), diphenylnitroasamine (DPN) and dimethylnitrosamine (DMN)] on both livers and testes of male rabbits through assessment of 17 β‐hydroxysteroid dehydrogenase (17 β‐HSD) activity. The protein expression of the three cytochrome P450s (CYP11A1, CYP19A1, and CYP21A2) is involved in the steroidogenesis. The levels of testosterone (T) and estradiol (E2) were also determined in the plasma of N‐nitrosamines‐treated rabbits after one, four‐, eight‐...
Incidence increased with age with the major burden in women >45 years. The majority had a patholo... more Incidence increased with age with the major burden in women >45 years. The majority had a pathologically confirmed diagnosis (91%), however 47% were at an advanced stage at presentation (regionally advanced 19.9%; metastatic 27%). The incidence correlated with educational level.
International Journal of Medical Microbiology, Apr 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitat... more Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH...
International Journal of Biological Macromolecules
A naturally occurring polyphenol called trans-resveratrol has received a lot of attention due to ... more A naturally occurring polyphenol called trans-resveratrol has received a lot of attention due to its possible health advantages for humans. The low solubility of trans-resveratrol and its isomerization upon UV exposure strongly limit its application as a skin-whitening agent. In the present study, to increase trans-resveratrol solubility, a new nanoformula was created by combining hydrophilic surfactants and oils. Trans-Resveratrol nanoformula has been prepared, characterized, and applied as a skin-whitening agent on the dorsal skin of Guinea pigs. The optimized trans-resveratrol nanoformula with a particle size of 63.49 nm displayed a single peak and a polydispersity index [0.36 ± 0.02]. In addition, the zeta potential of the optimized formula was −30.4 mV, confirming the high stability of this nanoformula. The melanin contents in the trans-resveratrol nanoformula-treated group were substantially lower than those of the control and the blank nanoformula-treated groups after staining of the dorsal skins [black areas] of guinea pigs with Fontana Mountain dye. The pigmentation index in the control, blank nanoformula, and optimized trans-resveratrol nanoformula were 329.4 ± 36.9, 335.8 ± 71.4, and 124.8 ± 19.6 respectively. Confirming this finding, immunohistochemistry analysis of skin tissues revealed that the expressions of melanogenesis-regulating proteins such as tyrosinase and microphthalmia-associated transcription factor were down-regulated. The safety of topical application of trans-resveratrol nanoformula was validated by no changes in free radical levels and oxidative stress markers proteins in the livers and kidneys of guinea pigs at the end of the experiment. Conclusions: A novel trans-resveratrol nanoformula as well as the mechanism whereby it promotes skin whitening effects were presented. Furthermore, the study illustrated that trans-resveratrol nanoformula is safe, non-toxic, and can be applied for skin whitening, although more research on human skin is needed.
Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain cau... more Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits. Western immunoblotting, spectrophotometric, and histological methods were used in this study. Tramadol (1.5 mg/kg body weight) was administered orally to male rabbits for up to three months (three times/week), and after pretreatment of rabbits with garlic (800 mg/kg) and/or selenium (1 mg/kg body weight) by 2 h. The present study showed that motilities, semen volumes, morphologies, sperm counts, testosterone, and estrogen levels were significantly decreased after 4, 8, and 12 weeks of tramadol treatment. In addition, the protein expressions of CYP 21A2, CYP 19, and 11A1 were down-regulated in the testes of the tramadol-treated rabbits. On the other hand, pretreatment of rabbits with garlic, selenium, and/or garlic-selenium for 2 h before administration of tramadol restored the downregulated CYP 21A2 and 11A1 to their normal levels after 12 weeks of tramadol treatment. Activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the testes of tramadol-treated rabbits. On the other hand, free radical levels were significantly increased in the testes of tramadoltreated rabbits for 12 weeks. Interestingly, such changes in the activities of antioxidant enzymes as well as free radical levels caused by tramadol were restored to their normal levels in the rabbits pretreated with either selenium, garlic, and/or their combination. Histopathological investigations showed that tramadol caused substantial vacuolization with the presence of damaged immature spermatozoid in the testes. However, selenium and garlic treatments showed an increase in healthy sperm production with normal mitotic and meiotic divisions. The present study illustrated for the first time the mechanisms of low steroid hormone levels in the testes of tramadol-treated rabbits which could be due to the downregulation of CYPs proteins, induction of oxidative stress, and inhibition of antioxidant enzyme activities. In addition, the present data showed that such toxic effects of tramadol were attenuated and restored to their normal levels after pretreatment of rabbits with garlic, selenium, and/or their combination. This finding may pave the way for a new approach to reducing the toxicity of tramadol.
The influence of Schistosoma mansoni infection on the capacity of the carcinogen-metabolizing enz... more The influence of Schistosoma mansoni infection on the capacity of the carcinogen-metabolizing enzymes was investigated prior to and after treatment of the infected male mice with praziquantel, an anti-schistosomal agent. The drug was administered in a daily dose of 60 mg/kg body weight for three days before decapitation at various infection intervals. After 20 and 30 days post-infection the hepatic content of cytochrome P-450 and cytochrome b-5 and the activity of aryl hydrocarbon hydroxylase were markedly increased. However, the constitutive levels of the above mentioned enzymes were significantly decreased at 45, 60 and 75 days post-infection. Treatment of the infected mice with praziquantel for three days, however, recovered the changes in these activities at each individual time point. Praziquantel showed no effect on either of the studied enzymes when administered alone except for that of NADPH-cytochrome C reductase activity which exhibited significant increase. The activity of NADPH-cytochrome C reductase gave inconsistent results after treatment of the infected animals with praziquantel. It is concluded that praziquantel can be considered as a safe and useful drug for the chemotherapy of schistosomiasis and it possessed a recovery for the activities of the drug-metabolizing enzyme.
Recently, different microbial ghosts (BGs) were prepared using a strategy based on the critical c... more Recently, different microbial ghosts (BGs) were prepared using a strategy based on the critical chemical concentrations. In the original protocol, it was given the name "Sponge Like" (SL) protocol. The protocol was reduced to be more reliable and given the name "Sponge Like Reduced Protocol" (SLRP). In this study, using SLRP we succeeded to prepare Klebsiella pneumoniae (KPGs) with correct 3D structure and surface antigens. The study has included oral, S/C, inhalation, I/P and I/M vaccination with KPGs and controlled with challenge test. Results of both the SLRP and the animal experiments prove that we have KPGs able to immunize rats subjected to different routes of administration against viable K. pneumoniae. The evaluation of the immune response include humoral and cellular immune responses, IFN-γ production, phagocytic activity, NBT reduction activity, serum agglutination titer and the bacterial load in the various tissues, was performed in BG-vaccinated animals subsequently challenged with K. pneumoniae. The results were compared with animals that were not immunized with the KPGs. KPGs not only are able to promote the generation of high titer antibodies and IFN-γ production but also are able to stimulate a significant increase in phagocytic activity, NBT reduction, a marked decrease in the bacterial load in the various tissues, indicated that the vaccine was able to induce clearance of intracellular K. pneumoniae. The protective effects of BG vaccination in rats against virulent K. pneumoniae were a result of the induction of a more effective immune response in vaccinated animals than that observed with the non-vaccinated animals. These findings demonstrate the potential of K. pneumoniae ghosts to be used as effective vaccines.
Journal of Infection and Public Health, Nov 1, 2019
BACKGROUND Human infection by Acinetobacter baumannii has been increased due to its resistance ag... more BACKGROUND Human infection by Acinetobacter baumannii has been increased due to its resistance against most of the antibiotics. Therefore, the present study aimed to design a candidate vaccine against A. baumannii infection. METHODS The protein and DNA contents of A. baumannii Ali190 were extracted using different critical concentrations of hydrogen peroxide, sodium hydroxide and sodium carbonate leading to the ghost of A. baumannii Ali190. Transmission and scanning electron microscope showed that it retained the 3D structure of its cell membrane. The ghost injected to rats via different routes of administrations including oral, subcutaneous, intramuscular, intraperitoneal, subcutaneous with adjuvant, and intramuscular with adjuvant. RESULTS β-Lactamase OXA-51 gene, is a predominant gene in all Acinetobacter strains, the gene was partially sequenced. The DNA sequence of OXA-51 gene showed 98% homology with A. baumannii isolate 6077/12 and also showed less homology percentage with other strains of Acinetobacter. A new strain of Acinetobacter has been deposited in Gene Bank under accession number MG062776. All routes of ghost administration showed full protection against live bacteria except oral administration showed 67% protection. On the other hand, all non-vaccinated rats did not survive after infection with live bacteria. SDS-gel electrophoresis of protein patterns of both A. baumannii and its ghost showed common protein bands with molecular weights 70, 60, and 23 kDa which were detected using western immunoblotting after raising the primary antibodies against A. baumannii ghost. The levels of INF-γ were significantly increased in all vaccinated groups, particularly in subcutaneous and subcutaneous with adjuvant compared to the control group. CONCLUSION With the exception of oral administration, all vaccinated rats via different routes of ABG administration showed full protection (100%) against live A. baumannii. However, 100% mortality rate was observed in non-vaccinated rats. Therefore, ABG could be useful as a candidate vaccine against A. baumannii infection.
Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liv... more Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liver injury. The combination of amoxicillin with clavulanic acid is commonly cited in such cases. Accordingly, the present study investigated the potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was hydrodistilled from the aerial parts of Salvia officinalis L. and its compositional analysis was characterized by Gas chromatography-Mass spectroscopy. Rats were treated singly or concomitantly with Co-amoxiclav and sage essential oil for a period of seven days. The major components of sage oil as identified by GC-MS were 1,8-cineole, β-pinene, camphor, β-caryophyllene, α-pinene and α-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5% respectively. The in vivo exposure of rats to Co-amoxiclav resulted in hepatotoxicity biochemically evidenced by the significant elevation of serum AST...
Although, there are several breakthroughs in the treatment of breast cancer on the past few decad... more Although, there are several breakthroughs in the treatment of breast cancer on the past few decades, high incidence of relapse and progression after conventional therapies is deeply concerning, indicating a great need for developing new therapeutics for breast cancer. In the present study, the anti-cancer effects of combinational therapy of Letrozole (Aromatase inhibitor) or Olaparib (PARP inhibitor) with Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), were examined on well differentiated ER-positive and poorly differentiated triple negative breast cancer cell lines, T-47D and MDA-MB-231, respectively. In addition, the effect of combined treatment was also examined by detecting cell survival, cell cycle analysis, and alterations in signaling pathway that play a role in breast cancer progression such as β -catenin, STAT3, cyclin D1, Bax, c-PARP, wild and Mutant p53. In addition the effect of combined treatments were examined on gene expression levels of Cytochromes; CYP1A1, ...
Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to ... more Infections with Pseudomonas aeruginosa (PA) pose a major clinical threat worldwide especially to immunocompromised patients. As a novel vaccine network for many kinds of bacteria, bacterial ghosts (BGs) have recently been introduced. In the present research, using Sponge-Like Reduced Protocol, P. aeruginosa ghosts (PAGs) were prepared to maintain surface antigens and immunogenicity. This is the first study, to our knowledge, on the production of chemically induced well-structured bacterial ghosts for PA using concentrations of different chemicals. The research was carried out using diabetic rats who were orally immunized at two-week intervals with three doses of PAGs. Rats were subsequently challenged either by the oral route or by the model of ulcer infection with PA. In challenged rats, in addition to other immunological parameters, organ bioburden and wound healing were determined, respectively. Examination of the scanning and transmission electron microscope (EM) proved that PAG...
Schistosomiasis ranks as one of the most important health prob-lems in developing countries with ... more Schistosomiasis ranks as one of the most important health prob-lems in developing countries with an estimated 200 millioninfected people in 72 different countries.In Egypt,bilharzialinfection is the most frequently found endemic parasitic disease.
Liver cancer is listed among the most common causes o f cancer-related death. Nowadays the clinic... more Liver cancer is listed among the most common causes o f cancer-related death. Nowadays the clinical diagnosis of early-stage hepatocellular carcinoma (HCC) has improved significantly; nevertheless, HCC prognosis is still highly poor. Therefore, new effective and well-designed therapeutic strategies are urgently recommended. Ruthenium complexes represent a new promising family of metal-based anticancer complexes that exhibit reduced toxicity compared to platinum (II) complexes c urrently used clinically. These complexes show a novel mechanism of action with different spectrum of activity compared to platinum-based drugs. The present study was performed to investigate the effect of new formulated Rhuthenium complex {Bis (quinolin-8-olato) bis (triphenylphosphine) Ruthenium(II)} (Ru(quin)2) with or without sorafenib; the gold standard treatment for advanced HCC, as a combined treatment on different molecular signaling pathway such as ERK1/2, Stat3, AKT/m- TOR and Wnt/β-catenin that are...
Journal of Musculoskeletal Surgery and Research, 2019
Osteoporosis is well recognized in children as a consequence of several factors. Therefore, the p... more Osteoporosis is well recognized in children as a consequence of several factors. Therefore, the present review sheds light on the role of diabetes mellitus (DM), malabsorption, glucocorticoids, nutrition, free radicals, and oxidative stress in the induction of osteoporosis. It may also provide valuable information regarding the early detection of osteoporosis to improve not only the bone health of schoolchildren but also their general quality of life. Measurement of bone mineral density (BMD) does not capture all the risk factors of bone fractures and/or osteoporosis. Therefore, bone resorption and formation markers such as osteoprotegerin; prolidase; osteocalcin; bone alkaline phosphatase and Vitamin D; parathyroid hormones; and macroelements such as calcium, phosphorus, and magnesium should be measured beside BMD in the plasma of school-aged children. Moreover, endocrine abnormalities, high levels of free radicals, and induction of oxidative stress showed an adverse effect on the skeleton and cause osteoporosis. It has been found that there is a strong correlation between osteoporosis and DM, malnutrition, and glucocorticoids in both pediatric and adult patients. Inhibition of antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase, was found to increase the production of reactive oxygen species by osteoclasts. Therefore, oxidative stress and other factors are important mediators of bone loss and also osteoporosis. Furthermore, antioxidants should be provided to maintain bone integrity because a deficiency of antioxidant vitamins has been found in the osteoporotic children.
N‐nitrosamines are widely spread environmental pollutants of well‐known toxicity and carcinogenic... more N‐nitrosamines are widely spread environmental pollutants of well‐known toxicity and carcinogenicity in various animal species. These compounds are metabolically activated by cytochrome P450 system predominantly in the liver and in other tissues into more active metabolites leading to generation of both alkylating agents that alkylate DNA and reactive oxygen species. In the current study, we investigated the influence of four types of N‐nitrosamines that are commonly present in the environment [methyethylnitrosamine, (MEN), diethylnitrosamine (DEN), diphenylnitroasamine (DPN) and dimethylnitrosamine (DMN)] on both livers and testes of male rabbits through assessment of 17 β‐hydroxysteroid dehydrogenase (17 β‐HSD) activity. The protein expression of the three cytochrome P450s (CYP11A1, CYP19A1, and CYP21A2) is involved in the steroidogenesis. The levels of testosterone (T) and estradiol (E2) were also determined in the plasma of N‐nitrosamines‐treated rabbits after one, four‐, eight‐...
Incidence increased with age with the major burden in women >45 years. The majority had a patholo... more Incidence increased with age with the major burden in women >45 years. The majority had a pathologically confirmed diagnosis (91%), however 47% were at an advanced stage at presentation (regionally advanced 19.9%; metastatic 27%). The incidence correlated with educational level.
International Journal of Medical Microbiology, Apr 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitat... more Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH...
International Journal of Biological Macromolecules
A naturally occurring polyphenol called trans-resveratrol has received a lot of attention due to ... more A naturally occurring polyphenol called trans-resveratrol has received a lot of attention due to its possible health advantages for humans. The low solubility of trans-resveratrol and its isomerization upon UV exposure strongly limit its application as a skin-whitening agent. In the present study, to increase trans-resveratrol solubility, a new nanoformula was created by combining hydrophilic surfactants and oils. Trans-Resveratrol nanoformula has been prepared, characterized, and applied as a skin-whitening agent on the dorsal skin of Guinea pigs. The optimized trans-resveratrol nanoformula with a particle size of 63.49 nm displayed a single peak and a polydispersity index [0.36 ± 0.02]. In addition, the zeta potential of the optimized formula was −30.4 mV, confirming the high stability of this nanoformula. The melanin contents in the trans-resveratrol nanoformula-treated group were substantially lower than those of the control and the blank nanoformula-treated groups after staining of the dorsal skins [black areas] of guinea pigs with Fontana Mountain dye. The pigmentation index in the control, blank nanoformula, and optimized trans-resveratrol nanoformula were 329.4 ± 36.9, 335.8 ± 71.4, and 124.8 ± 19.6 respectively. Confirming this finding, immunohistochemistry analysis of skin tissues revealed that the expressions of melanogenesis-regulating proteins such as tyrosinase and microphthalmia-associated transcription factor were down-regulated. The safety of topical application of trans-resveratrol nanoformula was validated by no changes in free radical levels and oxidative stress markers proteins in the livers and kidneys of guinea pigs at the end of the experiment. Conclusions: A novel trans-resveratrol nanoformula as well as the mechanism whereby it promotes skin whitening effects were presented. Furthermore, the study illustrated that trans-resveratrol nanoformula is safe, non-toxic, and can be applied for skin whitening, although more research on human skin is needed.
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Papers by Salah Sheweita