Abd-Elhakim, Y. M., M. M. M. Hashem, K. Abo-EL-Sooud, H. A. Ali, A. Anwar, A. E. El-Metwally, E. A. Mahmoud, and G. G. Moustafa, "Involvement of tumor necrosis factor-α, interferon gamma-γ, and interleukins 1β, 6, and 10 in immunosuppression due to long-term exposure to five common food preservatives in rats.", Gene, pp. 144590, 2020. Abstract

BACKGROUND: /Aims Food preservatives are abundant in many products in the human environment. However, little is known about the impact of many food preservatives on the immune system and the immune related genes. Hence, this study aimed to evaluate the effects of five widespread food preservatives, including butylated hydroxyanisole (BHA), potassium sorbate (PS), sodium benzoate (SB), boric acid (BA), and calcium propionate (CP), on haemato-immune functions.

METHOD: Sixty Sprague-Dawley rats were assigned to groups orally administered water (control), BHA (0.09 mg/kg), PS (4.5 mg/kg), SB (0.9 mg/kg), BA (0.16 mg/kg) or CP (0.18 mg/kg) for 90 consecutive days. Leukogram and erythrogram profiles were assessed. Nitric oxide and immunoglobulin levels together with phagocytic and lysozyme activities were estimated. Histologic examinations and histomorphometric analysis of splenic tissues were performed. Variations in the mRNA expression levels of tumour necrosis factor alpha (TNF-α), interferon gamma (IFNγ), interleukin (IL)-1β, IL-6, and IL-10 were assessed.

RESULTS: Anemic conditions, thrombocytopenia, leucocytopaenia simultaneous with lymphocytopaenia, monocytopenia, and esinopenia have been obvious following long term exposure to the tested food additives. Prominent exhaustion was noted in immunoglobulin and NO levels and in lysozyme and phagocytic activities. IFNγ, TNF-α, IL-1β, IL-6, and IL-10 were obviously upregulated in the groups exposed to food preservatives.

CONCLUSION: These results confirmed that continued exposure to high levels of BHA, PS, SB, BA, and CP has haematotoxic and immunotoxic effects. Furthermore, these adverse effects are mediated by cytokine production.

Hashem, M. M., K. Abo-EL-Sooud, Y. M. Abd-Elhakim, Y. A. - H. Badr, A. E. El-Metwally, and A. Bahy-EL-Dien, "The long-term oral exposure to titanium dioxide impaired immune functions and triggered cytotoxic and genotoxic impacts in rats.", Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), vol. 60, pp. 126473, 2020. Abstract

BACKGROUND: Titanium dioxide "TiO, E171″ is a widely used food additive that exists in various everyday food products all over the world together with vast applications in cosmetics and industry. However, many toxicological aspects particularly following oral exposure still unclear.

METHODS: Hence, this study was planned to examine the effect of oral exposure of male Wistar rats to two doses of TiO (20 or 40 mg/kg b.wt.) through oral gavage once daily for 90 consecutive days on the blood components, immunity, cytotoxic, and genotoxic indicators.

RESULTS: A dose-dependent leukopenia, eosinophilia, neutrophilia, and thrombocytopenia were noted. Also, the immunoglobins G (IgG) and IgM were significantly elevated in TiO treated rats. The phagocytic activities, lysozyme, nitric oxide, and immunoglobulin levels were significantly depleted following TiO exposure. A significantly reduced lymphocyte proliferation but elevated LDH activity was prominent in TiO treated rats. Different pathological perturbations were observed in both splenic tissue and bone marrow. A marked increase in CD4 and CD8 immunolabeling was evident. A significant increase in the comet variables was recorded in response to the exposure of rats to the increasing level of TiO at both levels.

CONCLUSION: Overall, these results indicated that TiO could induce hematotoxicity, genotoxic, and immunotoxic alterations with exposure for long durations.

Abo-EL-Sooud, K., G. A. Swielim, S. M. EL-Gammal, and M. N. Ramsis, "Comparative Pharmacokinetics and bioavailability of marbofloxacin in geese (Anser Anser domesticus) after two sites of intramuscular administrations.", Journal of veterinary pharmacology and therapeutics, 2020. Abstract

The pharmacokinetics of marbofloxacin (MAR) was compared in geese (Anser Anser domesticus) after single intravenous (IV) and intramuscular (IM) (thigh and pectoral muscles) administrations of 5 mg/kg. Serum concentrations of MAR were determined with high-performance liquid chromatography (HPLC) method. Serum MAR concentrations versus time were analyzed by a noncompartmental method. After IV administration, MAR showed high volume of distribution at steady state (V ) of 5.24 ± 1.08 L/kg. The serum body clearance (Cl) and elimination half-life (T λz) of MAR were 0.79 ± 0.07 L hr  kg and 6.94 ± 1.12 hr, respectively. The peak of MAR serum concentrations C achieved at one and 0.50 hr after thigh and pectoral IM sites of injections, respectively, were 1.20 and 0.91 μg/ml. Significant differences were found in the mean absorption time (MAT), the systemic bioavailability (F%), and elimination parameters of MAR between two sites of injections, indicating that the absorption was fairly slow and complete after thigh IM injection. The pharmacokinetics of MAR in geese diverged according to the site of IM injection following a parallel study design. We recommend the thigh muscle as IM site of injection to obtain maximum concentrations of the administered drug in geese.

Bahr, M., M. Amer, K. Abo-EL-Sooud, A. Abdallah, and O. El-Tookhy, "Preservation Techniques of Stem Cells Extracellular Vesicles: A Gate for manufacturing of clinical grade therapeutic-Extracellular Vesicles and long-term Clinical trials.", International Journal of Veterinary Science and Medicine, vol. 8, issue 1, pp. 1-8, 2020. preservation_techniques_of_stem_cells.pdf
Abo-EL-Sooud, K., M. M. Hashem, Y. M. Abd-Elhakim, G. M. Kamel, M. M. E. Eleiwa, and A. Q. Gab-Allaha, "Effect of sodium nitrite exposure on the immune responses against of rift valley fever vaccine in mice ", International Journal of Pharmacy and Pharmaceutical Sciences , vol. 119, issue 7, pp. 28-31, 2019.
Atef, M., Abo-Baker YI EL-Gendi, N. A. Afifi, K. Abo-EL-Sooud, and H. Y. El-Zorba, "The influence of flunixin on the elimination and milk residual patterns of oxytetracycline in dairy goats", Veterinarski Arhiv, vol. 89, issue 2, pp. 169-182, 2019.
Abd-Elhakim, Y. M., G. G. Moustafa, M. M. Hashem, H. A. Ali, K. Abo-EL-Sooud, and A. E. El-Metwally, "Influence of the long-term exposure to tartrazine and chlorophyll on the fibrogenic signalling pathway in liver and kidney of rats: the expression patterns of collagen 1-α, TGFβ-1, fibronectin, and caspase-3 genes.", Environmental science and pollution research international, vol. 26, issue 12, pp. 12368–12378, 2019. Abstract

Colouring agents are highly present in diverse products in the human environment. We aimed to elucidate the fibrogenic cascade triggered by the food dyes tartrazine and chlorophyll. Rats were orally given distilled water, tenfold of the acceptable daily intake of tartrazine, or chlorophyll for 90 consecutive days. Tartrazine-treated rats displayed a significant rise (p < 0.05) in the mRNA levels and immunohistochemical localization of the renal and hepatic fibrotic markers collagen 1-α, TGFβ-1, and fibronectin and the apoptotic marker caspase-3. Moreover, a significant increment (p < 0.05) in the levels of AST, ALP, creatinine, and urea was evident in both experimental groups but more significant differences were noticed in the tartrazine group. Furthermore, we found a marked increment in the MDA level and significant declines (p < 0.05) in the levels of the SOD, CAT, and GSH enzymes in the kidney and liver from tartrazine-treated rats. The histological investigation reinforced the aforementioned data, revealing hepatocytes with fibrous connective tissue proliferation, apoptotic hepatocytes and periportal fibrosis with tubular necrosis, and shrunken glomeruli and interstitial fibrous tissue proliferation. We concluded that, even at the exposure to high concentrations for long durations, chlorophyll exhibited a lower propensity to induce fibrosis, apoptosis, and histopathological perturbations than tartrazine.

Hashem, M. M., Y. M. Abd-Elhakim, K. Abo-EL-Sooud, and M. M. E. Eleiwa, "Embryotoxic and Teratogenic Effects of Tartrazine in Rats.", Toxicological research, vol. 35, issue 1, pp. 75-81, 2019 Jan. Abstract

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 (3.97 ± 0.21 g and 27.3 ± 0.54 mm, respectively) and 4.5 mg/kg (3.48 ± 0.15 g and 23.22 ± 1.02 mm, respectively) than in the control group (4.0 ± 0.15 g and 30.01 ± 0.42 mm, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.