@tdb2.tanta.edu.eg
Pharmacology and Toxicology
Faculty of Pharmacy, Tanta University
Pharmacology, Drug Guides, Toxicology
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
R. M. Elgharabawy, E. Tousson, I. E. El Sayed, A. H. A. Abd El-Aleim, M. Elabd, D. Gebreel and A. S. Ahmed
OBJECTIVE
The limitations faced by conventional drug delivery systems are being overcome through the use of rapidly evolving cancer nanotherapeutics. Determining the manner in which the Ehrlich solid tumor (EST) is impacted by the new bioactive Alanda-loaded flax seed gum nanoparticles (Alanda NPs) functioning as an anti-carcinogenic agent represents the research objective of this paper.
MATERIALS AND METHODS
Identification of the functional groups, surface morphology, particle size, and zeta potential were among the characterizations and preparations made for the prepared nanoparticles. A Control group, a Flax Seed Gum group, a raw Alanda group, an Alanda NPs group, an EST group, and an induced EST treated with Alanda NPs group comprised the six groups respectively which the 60 female mice were separated into in this in vivo study.
RESULTS
Toxicity assessments for kidneys and liver were performed alongside the detection of total genomic DNA degradation. The zeta potential and the particle sizes for Alanda NPs were -25.60±0.38 mv and 40±0.28 nm, respectively, where the latter demonstrated a monodisperse spherical shape, per the findings. The use of Alanda NPs to treat EST was found to alle te the DNA damage, apoptosis, and renal and hepatic toxicity that EST induces. Additionally, the activation of oxidative stress and apoptosis causing the renal and hepatic toxicity induced by EST is counteracted by the scavenging of free radicals by the Alanda NPs.
CONCLUSIONS
A high degree of safety for effective cancer treatment was displayed by the newly developed oral nanoparticles while also demonstrating strong potential in vivo.
Manar M. El Tabaa, Maram M. El Tabaa, Rehab M. Elgharabawy, and Walaa G. Abdelhamid
Springer Science and Business Media LLC
Rasha Abdelhady, Simona Cavalu, Sameh Saber, Rasha Elmowafy, Nesreen Elsayed Morsy, Samar Ibrahim, Mahmoud Said Ibrahim Abdeldaiem, Mervat Samy, Marwa A. Abd-Eldayem, Ahmed Shata,et al.
Elsevier BV
Sameh Saber, Eslam E. Abd El-Fattah, Amir Mohamed Abdelhamid, Ahmed A.E. Mourad, Manal Ali Mahrous Hamouda, Amr Elrabat, Sahar Zakaria, Amira A. Haleem, Sherin Z. Mohamed, Rehab Mohamed Elgharabawy,et al.
Elsevier BV
Eman M. Khalaf, Hanan M. Hassan, Ahmed M. El-Baz, Ahmed Shata, Ahmed E. Khodir, Mahmoud E. Yousef, Rehab Mohamed Elgharabawy, Nehal A. Nouh, Safaa Saleh, Mashael M. Bin-Meferij,et al.
Elsevier BV
Simona Cavalu, Hossam Sharaf, Sameh Saber, Mahmoud E. Youssef, Amir Mohamed Abdelhamid, Ahmed A. E. Mourad, Samar Ibrahim, Shady Allam, Rehab Mohamed Elgharabawy, Eman El‐Ahwany,et al.
Wiley
Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF‐κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti‐inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO‐1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF‐κB signaling and its consequent target pro‐inflammatory mediators, IL‐6 and TNF‐α. In contrast, IL‐10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti‐inflammatory, antioxidant, and antiapoptotic properties.
Manar Mohammed El Tabaa, Maram Mohammed El Tabaa, Anis Anis, Rehab Mohamed Elgharabawy, and Nermeen Borai El-Borai
Elsevier BV
Amir Mohamed Abdelhamid, Mahmoud E. Youssef, Simona Cavalu, Gomaa Mostafa-Hedeab, Amal Youssef, Sara T. Elazab, Samar Ibrahim, Shady Allam, Rehab Mohamed Elgharabawy, Eman El-Ahwany,et al.
Frontiers Media SA
Ulcerative colitis (UC), an inflammatory bowel disease, is a chronic condition of a multifaceted pathophysiology. The incidence of UC is increasing internationally. The current therapies for UC lack relative effectiveness and are associated with adverse effects. Therefore, novel therapeutic options should be developed. It has been well documented that modulating the Nrf2/NFκB is a promising therapeutic target in inflammation. Carbocisteine is a mucoregulatory medication and its efficacy in COPD was found to be more closely related to its antioxidant and anti-inflammatory properties. Carbocisteine has not yet been examined for the management of UC. Hence, our approach was to investigate the potential coloprotective role of carbocisteine in acetic acid-induced colitis in rats. Our results revealed that carbocisteine improved colon histology and macroscopic features and subdued the disease activity as well. Additionally, carbocisteine attenuated colon shortening and augmented colon antioxidant defense mechanisms via upregulating catalase and HO-1 enzymes. The myeloperoxidase activity was suppressed indicating inhibition of the neutrophil infiltration and activation. Consistent with these findings, carbocisteine boosted Nrf2 expression along with NFκB inactivation. Consequently, carbocisteine downregulated the proinflammatory cytokines IL-6 and TNF-α and upregulated the anti-inflammatory cytokine IL-10. Concomitant to these protective roles, carbocisteine displayed anti-apoptotic properties as revealed by the reduction in the Bax: BCL-2 ratio. In conclusion, carbocisteine inhibited oxidative stress, inflammatory response, and apoptosis in acetic acid-induced UC by modulating the Nrf2/HO-1 and NFκB interplay in rats. Therefore, the current study provides a potential basis for repurposing a safe and a commonly used mucoregulator for the treatment of UC.
Manal M. Elbandrawy, Osama Sweef, Doaa Elgamal, Tarek M. Mohamed, EhabTousson, and Rehab M. Elgharabawy
Elsevier BV
Sameh Saber, Mohamed Nasr, Mohamed M.Y. Kaddah, Gomaa Mostafa-Hedeab, Simona Cavalu, Ahmed A.E. Mourad, Ahmed Gaafar Ahmed Gaafar, Sameh S. Zaghlool, Safaa Saleh, Mohamed M. Hafez,et al.
Elsevier BV
Rehab M. Elgharabawy, Ibrahim El Tantawy El Sayed, Nada Abd-Allah Rezk, and Ehab Tousson
Frontiers Media SA
Breast cancer remains the most common cause of cancer deaths among women globally. Ehrlich solid tumor (EST) is a transplantable tumor model for simulating breast cancer. This study aims to describe the protective role of costus (Saussurea lappa) root against EST-induced cardiac toxicity. Forty female mice were randomly and equally divided into four groups (G1, control group; G2, costus group; G3, EST group; G4, EST + costus). The results showed that compared to the control, EST induced a significant increase in lactate dehydrogenase, creatine kinase, creatine kinase myoglobin, aspartate aminotransferase, and alkaline phosphatase activities; in potassium, chloride ion, cholesterol, triglyceride, and low density lipoprotein levels; in DNA damage and cardiac injury; and in p53 and vascular endothelial growth factor expression. Conversely, EST induced a significant decrease in sodium ion and high density lipoprotein levels and Ki67 expression compared to the control. Treatment of EST with costus improved cardiac toxicity, lipid profiles, electrolytes, and apoptosis, and protected against EST. This indicates the potential benefits of costus as an adjuvant in the prevention and treatment of cardiac toxicity.
Rehab M. Elgharabawy, Ahmad H. Alhowail, Ashraf M. Emara, Maha A. Aldubayan, and Amira S. Ahmed
Elsevier BV
Amira S. Ahmed, Maha A. Aldubayan, Hatem A. Ahmed, Ahmed M. Refaat, Albatool S. Alsalloumi, Rawan A. Almasuood, and Rehab M. Elgharabawy
Springer Science and Business Media LLC
Amira S. Ahmed, Amal H. Al-Najjar, Hadeel Alshalahi, Waleed Mohammad Altowayan, and Rehab M. Elgharabawy
Mary Ann Liebert Inc
The aim of the study was to appraise the link between psoriasis and Helicobacter pylori, investigate the influence of H. pylori treatment on psoriasis severity, determine the cutoff value of haptoglobin as a psoriatic biomarker, and determine the most reliable predictor for psoriasis in patients with H. pylori. This study was carried out on 100 adult Saudi participants from the Security Forces Hospital (Riyadh, Kingdom of Saudi Arabia). All participants were allocated into 5 groups (20/group): controls (G1), psoriatic patients (G2), patients with H. pylori (G3), psoriatic patients with untreated H. pylori (G4), and psoriatic patients with treated H. pylori (G5). The study was approved by the ethics committee of Security Forces Hospital, Riyadh, Saudi Arabia. The psoriasis area and severity index (PASI) score, 13C-urea breath test (13C-UBT), C-reactive protein (CRP), haptoglobin, platelet P-selectin, cluster of differentiation 4/cluster of differentiation 8 (CD4/CD8) ratio, and lymphocyte percentages were recorded. The haptoglobin level was significantly elevated in psoriatic patients compared with G1. In G5, there was significant attenuation in the PASI score, P-selectin, CRP, CD4/CD8 ratio, and lymphocyte percentage compared with G4. There was a significant positive correlation between psoriasis severity and 13C-UBT. In addition, 13C-UBT and PASI scores were significantly positively correlated with CRP, platelet P-selectin, and percentage of lymphocytes. H. pylori plays a potential role in psoriasis pathogenesis. H. pylori treatment attenuates psoriasis severity. Haptoglobin could be utilized as a psoriatic biomarker with 1.95 g/L as the cutoff value. The most reliable predictor for psoriasis in infected patients with H. pylori is 13C-UBT.
Amira S. Ahmed, Wejdan S. Alotaibi, Maha A. Aldubayan, Ahmad H. Alhowail, Amal H. Al-Najjar, Sridevi Chigurupati, and Rehab M. Elgharabawy
Hindawi Limited
Objectives. This study screened for factors affecting coronavirus disease 2019 (COVID-19) incidence in type 1 diabetes mellitus (T1DM) patients, appraised vitamin D’s efficacy in preventing COVID-19, and assessed the effects of clinical characteristics, glycemic status, vitamin D, and hydroxychloroquine administration on COVID-19’s progression and severity in T1DM patients. Methods. This retrospective research on 150 adults was conducted at Security Forces Hospital, Riyadh, KSA. Participants were allocated to three groups (50/group): control, T1DM, and T1DM with COVID-19. Participants’ fasting blood glucose (FBG), glycated hemoglobin (HbA1c), complete blood count, vitamin D, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, lactate dehydrogenase (LDH), prothrombin time, activated partial thromboplastin time, D-dimer, liver and kidney function, and hydroxychloroquine treatment were retrieved and analyzed. Results. The percentages of comorbidities and not taking hydroxychloroquine were significantly higher among T1DM patients with COVID-19 than patients with T1DM only. Mean vitamin D level was significantly lower in T1DM with COVID-19 patients than in the other two groups. Vitamin D showed a significant negative correlation with LDH, CRP, ESR, ferritin, and D-dimer, which was the most reliable predictor of COVID-19 severity in T1DM patients. Conclusion. Comorbidities and vitamin D deficiency are risk factors for COVID-19 in patients with T1DM. Patients who do not take hydroxychloroquine and have higher FBG and HbA1c levels are vulnerable to COVID-19. Vitamin D may be useful for preventing COVID-19 in T1DM patients. Comorbidities, higher FBG and HbA1c levels, not taking hydroxychloroquine, and vitamin D inadequacy elevate COVID-19 progression and severity in patients with T1DM.
Hussein Mohammad Eldeeb, Rehab M. Elgharabawy, Alaa E Abd Elmoniem, and Ahmed Ali Ahmed
SAGE Publications
The hypertension (HTN) and type 2 diabetes mellitus (T2DM) are a common multifactorial disease due to genetics and environmental factors. The alpha 2B adrenergic receptor (α2B-AR) has relationship with secretion of insulin and mediates the vasoconstriction that elevate blood pressure. This study aimed to determine the association between α2B-AR gene polymorphism with HTN and T2DM in Saudi cases. 200 cases and 100 healthy controls from Saudi population were recruited from the Internal Medicine clinic, Qassim University. The patients were grouped into: 72 HTN without T2DM; 62 HTN with T2DM and 66 T2DM only. Full medical history, examination and biochemical assays were performed for all participants. Genomic DNA was isolated from blood lymphocytes of all subjects for detection of α2B-AR gene polymorphism by using polymerase chain reaction (PCR). The results found a significant association between D carriers genotype and HTN with T2DM cases ( p < 0.05) as well as with T2DM-only cases, ( p < 0.05) compared to control. Regardless of HTN status, only cases with HTN and T2DM as well as those with T2DM were significantly associated with the recessive model DD versus II+ID ( p < 0.05). So, D carriers genotype was significantly associated with total cases of HTN and T2DM ( p < 0.05) compared to controls. Our results suggested that there is a relationship between the α2B-AR I/D gene polymorphism and the risk for T2DM with or without HTN, but no such comparable relationship is evident with HTN-only cases among Saudi population in Qassim region.
Ashraf Mahmoud Emara, Khaled Ali Alrasheedi, Salha Dihim Alrashidi, and Rehab Mohamed Elgharabawy
Informa UK Limited
Abstract The objective of this research was to evaluate consequences to the immune system of long-term exposure to waste anesthetic gases (WAG) by medical theater personnel. Two groups were recruited: (i) 60 healthy male controls; (ii) 120 medical professionals exposed to WAG, subdivided according to theater role, i.e. surgeons, surgical assistants (SA), anesthetists, anesthetic assistants (AA), nurses, and workers. Serum levels of fluoride, hexafluoroisopropanol (HFIP), total lymphocyte counts, as well as of CD3, CD4, and CD8 cells, CD4/CD8 ratios, and immunoglobulins IgA, IgG, IgM, and IgE were assayed. The results showed that fluoride and HFIP titers were significantly increased in anesthetists and AA compared with the other exposed groups. All exposed groups demonstrated significant elevation in lymphocyte count, CD4+ cell levels, CD4/CD8 ratios, as well as levels of IgE, IgM and IgG compared with the controls. With regard to the latter outcomes, a significant increase in IgE was seen in the surgeon, nurse, and worker groups compared with the other professions. Surgeons, anesthetists and AA exhibited higher IgM titers compared with their colleagues. Significantly higher IgG levels were identified in the SA, anesthetists, AA, and workers than in their nurses and surgeon coworkers. Of the six sub-groups, only the anesthetists and their assistants (AA) displayed a significant increase in CD4+ cells and CD4/CD8 ratios and a decrease of CD8+ cells compared with the controls. This spectrum of results suggests that variation exists in immunomodulatory responses to WAG exposure amongst hospital personnel.
A. Alhowail, S. Chigurupati, R. Elgharabawy and M. Aldubayan
OBJECTIVE
Doxorubicin (DOX) is a chemotherapeutic agent widely used to treat cancers, particularly breast cancer. DOX has side effects, including cardiotoxicity, hepatotoxicity, and nephrotoxicity. Imipramine is an antidepressant that increases the release of neurotransmitters. This study aimed to investigate the effect of co-administration of imipramine and DOX on DOX-induced toxicity.
MATERIALS AND METHODS
Forty female mice (10-12-weeks-old, 30-38 g) were divided into four groups (n = 10 per group). The animals in the control group received a single-dose saline injection. The animals in the DOX group received a single dose of DOX (20 mg/kg) by intraperitoneal (i.p.) injection. The animals in the imipramine group received the drug daily in their drinking water (0.13 mg/mL) for 9 days, starting 1 day before the DOX injection received by the DOX group. The animals in the combination group (DOX+imipramine) received a single dose of DOX (20 mg/kg, i.p. injection), and a daily dose of imipramine in their drinking water (0.13 mg/mL) for 9 days starting 1 day before the DOX injection. The animals were observed daily to record mortality, and their body weights were recorded every alternate day.
RESULTS
DOX treatment increased the rate of mortality compared with that for control animals. Imipramine co-administration with DOX increased the rate of mortality significantly (p < 0.05) compared with DOX treatment alone. The mortality rate in both the control and imipramine-treatment groups was zero. DOX co-administered with imipramine resulted in significantly reduced body weight compared with control animals.
CONCLUSIONS
The combination of DOX and imipramine reduced the survival rate of female mice, suggesting that imipramine increases the toxic effects of DOX.
Ehab Tousson, Ezar Hafez, Somia Zaki, Amani Gad, and Rehab M. Elgharabawy
Elsevier BV
AM Emara, KA Alrasheedi, MA Aldubayan, AH Alhowail, and RM Elgarabawy
SAGE Publications
A significant health risk exists within a section of health workers that are exposed to anaesthetic gas and vapours, found in the atmosphere of treatment or operating rooms. These compounds are classified as waste anaesthetic gases (WAG). The present study aimed at identifying alterations in hepatic and haematological parameters occurring as a result of chronic exposure to WAG potentially affecting the health of team members working in hospitals. Therefore, operating room operatives, vulnerable to long-standing WAG exposure, were recruited for this study. Sevoflurane anaesthesia metabolites (inorganic fluoride and hexafluoroisopropanol (HFIP)), haematological indices and liver toxicity markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and osteopontin) were measured. The collected results showed increased plasma inorganic fluoride, HFIP and liver toxicity markers, as well as disturbances in haematological parameters. In conclusion, exposure to halogenated inhalational anaesthetics, in general, and Sevoflurane, in particular, induces alterations in hepatic markers and haematological indices.
Maha A. Aldubayan, Amira S. Ahmed, Ashraf M. Emara, Ahmed A. Ahmed, and Rehab M. Elgharabawy
Hindawi Limited
The main avoidable risk factor for cardiovascular conditions is high blood pressure (hypertension). At global level, hypertension is believed to be responsible for a 54% stroke-related mortality rate and a 47% mortality rate associated with coronary heart disease. It is postulated that sinapic acid (SA) could help in hypertension management because it displays robust antioxidant, antihyperglycemic, and peroxynitrite scavenging effects. To explore this hypothesis, this work examined the effect of SA on oxidative stress and cardiovascular disease in rats with hypertension by comparison against captopril. For this purpose, 50 male rats were used and equally allocated to five groups, namely, normal control, positive control (L-NAME), L-NAME with concomitant captopril administration, L-NAME with concomitant SA administration, and L-NAME with concomitant administration of both SA and captopril. Results showed that, by contrast to control, L-NAME exhibited marked elevation in serum CK-MB, total cholesterol, triglycerides, VLDL-C, LDL-C, Ang II, AT2R, ET-1, and angiopoietin-2; on the other hand, L-NAME exhibited marked reduction in serum HDL-C, superoxide dismutase (SOD) activity, nitric oxide synthase 3 (NOS3), and glutathione (GSH). Furthermore, joint administration of SA and captopril ameliorated hypertension, enhanced cardiovascular function, hindered hyperlipidemia, and decreased oxidative stress and myocardial hypertrophy displayed by rats with hypertension. Based on such findings, better chemopreventive or therapeutic approaches can be devised to manage hypertension and cardiovascular conditions.
Mohamed L. Salem, Sabry A. El-Naggar, Maysa A. Mobasher, and Rehab M. Elgharabawy
Hindawi Limited
One of the activating factors of the cells of the innate immune system is the agonists of toll-like receptors (TLRs). Our earlier publications detailed how poly(I:C), a TLR3 agonist, elevates the NK cell population and the associated antigen-specific CD8+T cell responses. This study involved a single treatment of the B6 mice with poly(I:C) intraperitoneally. To perform a detailed phenotypic analysis, mononuclear cells were prepared from each of the liver, peripheral blood, and spleen. These cells were then examined for their NK cell population by flow cytometric analysis following cell staining with indicated antibodies. The findings of the study showed that the NK cell population of the liver with an NK1.1highCD11bhighCD11chighB220+Ly6G-phenotype was elevated following the treatment with poly(I:C). In the absence of CD11b molecule (CR3-/-mice), poly(I:C) can still increase the remained numbers of NK cells with NK1.1+CD11b-and NK1.1+Ly6G-phenotypes in the liver while their numbers in the blood decrease. After the treatment with anti-AGM1 Ab, which induced depletion of NK1.1+CD11b+cells and partial depletion of CD3+NK1.1+and NK1.1+CD11b-cell populations, poly(I:C) normalized the partial decreases in the numbers of NK cells concomitant with increased numbers of NK1.1-CD11b+cell population in both liver and blood. Regarding mice with a TLR3-/-phenotype, their injection with poly(I:C) resulted in the partial elevation in the NK cell population as compared to wild-type B6 mice. To summarise, the TLR3 agonist poly(I:C) results in the elevation of a subset of liver NK cells expressing the two myeloid markers CD11c and CD11b. The effect of poly(I:C) on NK cells is partially dependent on TLR3 and independent of the presence of CD11b.
Maha A. Aldubayan, Rehab M. Elgharabawy, Amira S. Ahmed, and Ehab Tousson
Hindawi Limited
Interest is growing in finding natural sources of effective antitumor agents that generate fewer side effects than conventional chemotherapeutic drugs. Avenanthramides (Avns) are such compounds; these phenolic molecules naturally occur in oats and have antioxidant, anti-inflammatory, and antiproliferative effects making them worthy of further research. The aim of this study is to characterise Avns’ curative ability and antineoplastic activity on solid-form Ehrlich tumors. For the study, 75 female mice were randomly and equally allocated to five groups (group 1-control, group 2-DMSO, group 3-positive control receiving Avns, group 4-mice with Ehrlich solid tumor, and group 5-Ehrlich solid tumor treated with Avns). Mice with Ehrlich solid tumors exhibit increased tumor volume; elevated expression of AFP, ALT, AST, Bcl2, CEA, cholesterol, creatinine, urea, MDA, PCNA, potassium, triglycerides, TNF-α, and NF-κB; and a concomitant decline in catalase, GSH, P53, and SOD. In the mice with Ehrlich tumors who received Avns, there appeared to be improvement in NF-κB TNF-α, tumor markers (AFP and CEA), electrolytes, liver and kidney function enzymes, and lipid profiles; reduced MDA level; improved antioxidant parameters; normalised liver protein, P53, and PCNA; and reduced Bcl2 expression. Pathological examination of tumor lesions also indicated improvement. These results suggest that Avns exhibit antineoplastic activity and possess antioxidant properties that enhance the antioxidant defence system, thus reducing the oxidative stress caused by Ehrlich solid tumors.
RM Elgharabawy, DM Elgharbawy, and AM Emara
SAGE Publications
Reactive oxygen species have a significant role in the pathogenesis of iron oxide nanorod (IONR) overload-induced organ toxicity in some organs such as the lungs. Green tea induces upregulation of phase II antioxidant enzymes that are transcriptionally organized by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that when activated antagonize the oxidative stress induced by IONR overload that causes cardiotoxicity. The aim of the present study was to determine whether treatment of cardiotoxicity with iron chelators (deferiprone (DFP) or deferoxamine (DFO)) alone or in combination with phytochemical activation of Nrf2 (green tea) can protect cardiomyocytes from IONR overload-induced cardiotoxicity. One hundred five rats were distributed into seven groups: two control groups (non-IONR-overloaded and IONR-overloaded) and five IONR-overloaded groups such as a green tea group, DFP group, DFP combined with green tea group, DFO group, and DFO combined with green tea. Blood samples and cardiac tissues were obtained for estimation of total iron-binding capacity, ratio of myocardial 8-hydroxy-2′-deoxyguanosine/myocardial 2-deoxyguanosine, thiobarbituric acid reactive substances, glutathione (GSH) contents, and histopathological examination. The results showed mild histopathological changes in the heart and a significant decrease in all biochemical parameters, except for myocardial GSH, in the DFP group. The addition of green tea improved the biochemical and histopathological results compared with chelators alone.
Mohamed L Salem, Sabry A El-Naggar, Heba A Mahmoud, Rehab M Elgharabawy, and Abeer M Bader
SAGE Publications
Although the majority of cancers respond to chemotherapy, most cancer types relapse, at least in part, due to the poor immunogenicity of most tumor. We have reported before that treatment of tumor bearing mice with a combination of the anti-cancer chemotherapy cyclophosphamide (CTX) and immunotherapy can result in complete tumor regression using T-cell receptor (TCR) transgenic CD8+T cells specific to antigens. This study aimed to determine whether chemotherapy can cure immunogenic tumor which expresses non-self-tumor antigen and result in antitumor immunity. Either EL4 cell line, a poorly immunogenic thymoma, or EG7, a clone of EL4 cells transfected with ovalbumin (OVA), as a non-self-antigen were inoculated subcutaneously into wild type or splenectomized C57BL/6 mice and then treated once with intraperitoneal (i.p.) injection of 4 mg CTX/mouse. In certain experiments, the mice were rechallenged with the same tumor type 1–2 months after the primary challenge. Treatment of EL4 bearing mice with CTX induced transient antitumor effect followed by tumor progression. Interestingly, however, treatment of EG7-bearing mice with CTX resulted in regression of early and advanced tumors. EG7 tumor-free mice rejected the second and the third challenges with EG7 cells, but not with challenge EL4 cells. These antitumor effects did not require spleen, since splenectomized mice showed similar antitumor effects of CTX on EG7 cells. Taken together, these data indicate that expression of non-self-antigen by poorly immunogenic tumor might be a reliable means to increase its immunogenicity and its response to chemotherapy.