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.

Abo-EL-Sooud, K., M. M. Hashem, Y. A. Badr, M. M. E. Eleiwa, A. Q. Gab-Allaha, Y. M. Abd-Elhakim, and A. Bahy-EL-Dien, "Assessment of hepato-renal damage and genotoxicity induced by long-term exposure to five permitted food additives in rats.", Environmental science and pollution research international, vol. 25, issue 26, pp. 26341-26350, 2018 Sep. Abstract

The present study assessed the long-term daily administration of benzoic acid (BA), potassium sorbate (PS), chlorophyll (CPL), tartrazine (TAZ), and butylated hydroxyanisole (BHA) on hepato-renal changes and DNA damage in rats. Animals were orally administered with the 10 times of the acceptable daily intake (ADI) from each tested substance daily for 60 consecutive days. Blood, liver, and kidney samples were collected to evaluate hematological, biochemical, histopathological, and genotoxic alterations. The extent of liver and kidney damage was evaluated by comet assay and histopathologically. Significant reduction of leukocyte numbers and lymphocytes % in CPL- and TAZ-treated rats. However, significant increases in platelet count in all treated groups after 60 days were detected. The levels of serum transaminases enzymes (ALT, AST), alkaline phosphatase (ALP), and creatinine were significantly increased in all treatments except with BHA group, but no substantial differences were found in urea after 60 days. Aside from BHA, results of DNA damage revealed significant increases in tailed nuclei, tail moment, DNA% in the tail, and tail length in liver and kidney at different degrees. Moreover, the histopathological figures of liver and kidneys affirmed destructive and degenerative changes. The study indicates that most of the tested food additives may provoke genotoxicity and hepato-nephropathy, which could be serious for human health. Therefore, it is necessary to be informed about the hazardous effects of food additives and more attention should be focused towards using natural substitutes.

Abdel-Daim, M. M., K. Abo-EL-Sooud, L. Aleya, S. G. Bungau, A. Najda, and R. Saluja, "Alleviation of Drugs and Chemicals Toxicity: Biomedical Value of Antioxidants ", Oxidative Medicine and Cellular Longevity, vol. 2018, issue 6276438, 2018.
Khaled, A. - E. L. - S., "Hypnotic and general anaesthetic effects of Citrus aurantium L. oil on rats", 3rd Global Summit on Herbals & Traditional Medicine, Osaka, Japan, 18-20 October, pp. 8, 2017.
Khaled, A. - E. L. - S., F. A. Ahmed, S. A. El-Toumy, H. S. Yaecob, and H. M. ELTantawy, "Phytochemical, anti-inflammatory, anti-ulcerogenic and hypoglycemic activities of Periploca angustifolia L extracts in rats", Clinical Phytoscience, vol. 4, issue 27, pp. 1-8, 2018.
Abdel-Daim, M. M., S. M. Aly, K. Abo-EL-Sooud, M. Giorgi, and S. Ursoniu, "Role of Natural Products in Ameliorating Drugs and Chemicals Toxicity.", Evidence-based complementary and alternative medicine : eCAM, vol. 2016, pp. 7879406, 2016.
Abd-Elhakim, Y. M., M. M. Hashem, A. Anwar, A. E. El-Metwally, K. Abo-EL-Sooud, G. G. Moustafa, S. M. Mouneir, and H. A. Ali, "Effects of the food additives sodium acid pyrophosphate, sodium acetate, and citric acid on hemato-immunological pathological biomarkers in rats: Relation to PPAR-α, PPAR-γ and tnfα signaling pathway.", Environmental toxicology and pharmacology, vol. 62, pp. 98-106, 2018 Sep. Abstract

The food additives sodium acid pyrophosphate (SAPP), sodium acetate (SA), and citric acid (CA) were evaluated for their hemato-immunotoxic effects. Forty adult Sprague-Dawley rats were distributed into four groups and were orally administered water, SAPP (12.6 mg/kg), CA (180 mg/kg), or SA (13.5 mg /kg) daily for 90 days. Erythrogram and leukogram profiles were evaluated. The levels of lysozyme, nitric oxide, immunoglobulin, and phagocytic activity were measured. Histologic and immunohistochemical evaluations of splenic tissues were performed. Changes in the mRNA expression levels of peroxisome proliferator-activated receptor α and γ (PPAR-α and PPAR-γ), and tumor necrosis factor α (TNF-α) genes were assessed. A significant leukopenic condition was observed with SAPP, while CA induced marked leukocytosis, and SA showed a lymphocytosis condition. Both the innate and humoral parameters were significantly depressed. Various pathological lesions were observed, including diffuse hyperplasia of the red pulp, depletion of the white pulp, and capsular and parenchymal fibrosis. A marked decrease in CD3 T-lymphocyte and CD20 B-lymphocyte immunolabeling in rats treated with SAPP and SA was evident. Marked downregulation of PPAR-α and PPAR-γ together with upregulation of TNF-α was recorded. These results indicate that high doses of SAPP, SA and CA exert hematotoxic and immunotoxic effects with long-term exposure.

Abo-EL-Sooud, K., M. M. Hashem, Y. M. Abd ElHakim, G. M. Kamel, and A. Q. Gab-Allaha, "Effect of butylated hydroxyl toluene on the immune response of Rift Valley fever vaccine in a murine model.", International immunopharmacology, vol. 62, pp. 165-169, 2018 Sep. Abstract

The present study was planned to examine the effect of butylated hydroxy toluene (BHT) on the immune response of Rift Valley fever vaccine (RVFV) in Swiss mice. Animals were divided into four equal groups. The first group was kept as negative control. The 2nd group was orally administrated with the acceptable daily intake (ADI) of BHT 0.3 mg/kg b.wt. daily for 21 days and the 3rd group were vaccinated only by inactivated RVFV at a dose of 0.2 ml I/P two times. The 4th group was orally administrated BHT as in the 2nd group and vaccinated by inactivated RVFV as in the 4th group. Blood samples were collected from all groups two weeks from booster vaccination. The cellular immunity was determined by leucocytic indices and the neutrophil-lymphocyte ratio (NLR) whereas, humoral immunity was evaluated with IgG antibodies titer using enzyme-linked immune-sorbent assay (ELISA) test, serum neutralization test (SNT) and challenge test. BHT induced leucopenia, neutrophilia and marked lymphocytopenia in both non-vaccinated and vaccinated mice. Moreover, BHT significantly decreased the efficiency of vaccination by inducing 70% cytopathic effect (CPE) in the infected cell cultures and increasing the ED value of RVFV vaccine. The present study indicates that BHT possesses a potential for decreasing both cellular and humoral mediated mechanisms.

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