Toll-like receptors and nuclear factor kappa B signaling pathway involvement in hepatorenal oxidative damage induced by some food preservatives in rats.

Chemical food preservatives are extensively found in various processed food products in the human environment. Hence, this study aimed to investigate the effect of long-term exposure to five food preservatives (potassium sorbate (PS), butylated hydroxyanisole (BHA), sodium benzoate (SB), calcium propionate (CP), and boric acid (BA)) on the liver and kidney in rats and the probable underlying mechanisms. For 90 days, sixty male albino rats were orally given either water (control), 0.09 mg/kg b.wt BHA, 4.5 mg/kg b.wt PS, 0.9 mg/kg b.wt SB, 0.16 mg/kg b.wt BA, or 0.18 mg/kg b.wt CP. Liver and kidney function tests were assessed. Hepatic and renal oxidative stress biomarkers were estimated. Histologic examination analysis of liver and kidney tissues was achieved. Toll-like receptors 2 and 4 (TLR-2 and TLR-4), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels were measured. The results revealed that long-term oral dosing of the five food preservatives resulted in significant increases in alkaline phosphatase, alanine transaminase, aspartate transaminase, urea, uric acid, and creatinine levels. There were significant reductions in hepatic and renal antioxidant enzymes, an increase in MDA concentrations, and pathological alterations in renal and hepatic tissues. The mRNA levels of TLR-4, TLR-2, NF-κB, and TNF-α were elevated in the food preservatives-exposed groups. Conclusively, the current findings revealed that long-term exposure to PS, BHA, SB, CP, and BA has a negative impact on liver and kidney function. Furthermore, these negative effects could be mediated via oxidative stress induction, inflammatory reactions, and cytokine production.

Effect of Selenium Nanoparticles and/or Bee Venom against STZ-Induced Diabetic Cardiomyopathy and Nephropathy.

The main purpose of our study was to examine the role of selenium nanoparticles (SeNPs) and/or bee venom (BV) in ameliorating diabetic cardiomyopathy (DCM) and nephropathy (DN) at the biochemical, histopathological and molecular levels. Fifty male albino rats were used in this experiment, divided into five groups: control, Streptozocin (STZ) diabetic, STZ-diabetic treated with SeNPs, STZ-diabetic treated with BV, and STZ-diabetic treated with SeNPs and BV. Biochemically, STZ injection resulted in a significant increase in serum glucose, BUN, creatinine, CRP, CK-MB, AST, LDH and cardiac troponins with a significant decrease in the serum insulin and albumin concentrations. Histopathologically, STZ injection resulted in diabetes, as revealed by glomerulonephritis, perivascular hemorrhage, inflammatory cell infiltrations and fibrosis, with widening of interstitial spaces of cardiomyocytes, loss of muscle cells continuity and some hyaline degeneration. At the molecular levels, the expression levels of miRNA 328, miRNA-21, TGFß1, TGFß1R, JAK1, STST-3, SMAD-1 and NFκß genes were significantly up-regulated, whereas the expression levels of SMAD-7 were significantly down-regulated. It is concluded that SeNPs and/or BV administration ameliorates the deleterious effects resulting from STZ administration through improving the biochemical, histopathological and molecular effects, suggesting their protective role against the long-term diabetic complications of DCM and DN.

GC-MS Analysis of Bioactive Compounds Extracted from Plant Rhazya stricta Using Various Solvents.

Worldwide, human beings have traditionally employed many folkloric herbal resources as complementary and alternative remedies, and these remedies have played a pivotal role in modern medicines for many decades, as scientists have used them to develop drugs. We studied the effects of employing solvents with varying polarity on the yields of phytochemical components extracted from the plant Rhazya stricta. We used chloroform-methanol (1:1), methanol, ethanol, diethyl ether, and ethyl acetate as extraction solvents. The results showed that the efficiencies of the solvents at extracting phytochemical compounds were in this order: chloroform-methanol < ethanol < methanol < diethyl ether < ethyl acetate extract. The chloroform-methanol extract produced the highest concentration of phenolic and flavonoid contents among the five solvents tested (13.3 mg GAE/g DM and 5.43 CE/g DM). The yields of the extracted phytochemical compounds ranged from 47.55 to 6.05%. The results revealed that the properties of the extraction solvents considerably impacted the extraction yield and the phytochemical components of the R. stricta extract. Furthermore, compared with the other solvents, the chloroform-methanol extraction led to the highest yield (47.55%) and to more phytochemical substances being extracted. The aim of this study is to investigate the phytochemical compounds extracted from R. stricta with different solvents that have different polarities.

Modulation of immune functions, inflammatory response, and cytokine production following long-term oral exposure to three food additives; thiabendazole, monosodium glutamate, and brilliant blue in rats.

The food additives thiabendazole (TBZ), monosodium glutamate (MSG), and brilliant blue (BB) are commonly used in many daily-consumed food products worldwide. They are widely used in major agricultural and industrial applications. Yet, many of its toxicological aspects are still unclear, especially immune modulation. This research was therefore intended to investigate the effects of male Wistar rats' daily oral exposure for 90 days to TBZ (10 mg/kg b.wt), MSG (20 mg/kg b.wt), or BB (1.2 mg/kg b.wt) on the blood cells, immunity, and inflammatory indicators. The three tested food additives showed varying degrees of hematological alterations. Initially, megaloblastic anemia and thrombocytopenia were evident with the three tested food additives. At the same time, TBZ showed no significant changes in the leukogram element except eosinopenia. MSG induced leukopenia, lymphocytopenia, neutrophilia, and eosinophilia. BB evoked neutrophilia and lymphopenia. The immunoglobins M (IgM) and IgG were significantly reduced with the three tested food additives. In contrast, lysozyme and nitric oxide levels were elevated. A reduced considerably lymphocyte proliferation was detected with TBZ and MSG exposure without affecting the phagocytic activity. Various pathologic disturbances in splenic tissues have been detected. An obvious increase in CD4+ but a lessening in CD8+ immunolabeling was evident in TBZ and MSG groups. The cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin 1ß, 6, 10, and 13, were significantly upregulated in the spleen of rats exposed to TBZ, MSG, and BB. These results concluded that TBZ, MSG, and BB negatively affect hematological parameters, innate and humoral immune functions together with inflammatory responses. TBZ achieved the maximal negative impacts followed by MSG and finally with BB. Given the prevalence of these food additives, TBZ and MSG should be limited to a minimal volume use, or natural food additives should be used instead.

Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes.

BACKGROUND/AIMS: Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage. METHOD: Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800 mg/kg bw), ML (700 mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined. RESULTS: ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats. CONCLUSION: MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.

Different kinetics of chicken interferon-alpha signalling transduction responses following immunization of broiler chickens with different Newcastle disease virus vaccines and infection with virulent genotype VIId strain.

Newcastle disease virus (NDV) is a highly contagious and notifiable avian disease leading to grave economic losses in the poultry industry. Although the immune responses against NDV have been widely investigated, little is known regarding the virus interaction with the host innate immune responses. In this study, we tested the effect of different commercially applied Newcastle disease vaccines as well as virulent NDV genotype VIId on the expression pattern of the upstream regulator and downstream effector genes related to chicken interferon-alpha (chIFNα) signalling transduction pathway. Using quantitative real-time PCR analysis, mild transient induction of chIFNα-inducible genes was detected in bird spleen 72 h post-vaccination (hpv) with either live LaSota (respiratory) or VG/GA (enteric) strains. Vaccination with the enteric VG/GA strain led to stimulation of the investigated pathway as early as 24 hpv which continued up to 7 days in bird caecal tonsils. Subcutaneous injection with inactivated LaSota oil adjuvant-based vaccine led to continual stimulation of the investigated pathway up to 7 days post-vaccination (dpv). The recombinant herpesvirus of turkey (rHVT) - NDV vaccine led to remarkable stimulation of all the tested cytokines up to 17 dpv in comparison with LaSota and VG/GA NDV vaccines. Stronger but transient activation of all the tested cytokines was detected in spleens during the first 24 h post-challenge with virulent NDV (vNDV) which reduced gradually and diminished later due to the virus-induced lymphocytic depletion. This study will aid in the discovery of new approaches to control NDV.

The role of sulpiride in attenuating the cardiac, renal, and immune disruptions in rats receiving clozapine: mRNA expression pattern of the genes encoding Kim-1, TIMP-1, and CYP isoforms.

The present study was aimed to explore the cardio-, immuno-, and nephrotoxic effects of the antipsychotic agent clozapine (CLZ) and the alleviative potency of sulpiride (SPD) on these impairments in rats. For this purpose, 40 male rats were divided into four groups and were orally treated with saline (control), CLZ (0.5 mg/kg bw), SPD (28 mg/kg bw), or a combination of CLZ and SPD (CLZ+SPD), daily for 30 consecutive days. At necropsy, blood samples and specimens from the heart, kidneys, and spleen were collected for biochemical, molecular, and histopathological investigations. The results showed that CLZ administration was associated with significantly lower immune status indices and increased serum levels of pro-inflammatory cytokines, lactate dehydrogenase, malondialdehyde, cardiac, and renal tissues injury markers. Moreover, the mRNA expression levels of Kidney Injury Molecule-1 (Kim-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and cytochrome P450 (CYP) isoforms were markedly upregulated in CLZ-treated rats, compared to the control group. On the other hand, rats treated with SPD alone showed non-significant differences in terms of immune response indices, tissue injury markers, and mRNA expression levels of Kim-1, TIMP-1, and CYP isoforms. Finally, CLZ+SPD co-treatment significantly modulated almost all biochemical indices. Besides, Kim-1, TIMP-1, and CYP2C19 mRNA expression levels were significantly downregulated, while other CYP isoforms showed no modulation, compared with CLZ-treated group. Histopathologically, CLZ-treated rats showed severe lesions in renal, splenic, and cardiac tissues, compared with control rats, which were restored in CLZ+SPD-co-treated rats. Overall, these findings demonstrate that CLZ treatment induces significant cardiac, immune, and nephropathic alterations, which were reduced with CLZ+SPD co-treatment.

Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats.

The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats. Forty male adult albino rats were divided into 4 groups; the first one was considered as a control group, the others were orally administrated with 25, 50, and 100 b.wt. representing therapeutic, double therapeutic, and 4 times therapeutic doses, respectively, of tramadol HCL daily for 1 month. Serum and brain, hepatic, and renal tissues were collected for biochemical and molecular investigations. Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. At the same line, hepatic and renal 8-OHdG and MDA levels showed a significant increase with a significant decrease in reduced glutathione (GSH), CAT, and SOD activities. In addition, hepatic and renal function parameters including serum alanine amino transferase (ALT), aspartate amino transferase (AST), urea, and creatinine were increased in a dose-dependent manner. At the molecular levels, hepatic cytochrome P5402E1 (CYP2E1), renal Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) showed also a significant increase in the expression levels. Histopathological evaluation of the brain confirmed the above biochemical results. In conclusion, tramadol HCL induced neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress.

Shelf life extension of wheat bread by alhydwan flour and Carboxymethylcellulose and improvement of their quality characteristics, dough rheological and microstructure.

Alhydwan, has been used in bakery products for many years in South of Yemen. Alhydwan primary function in bakery products is to inhibit moisture content during storage, leading to improved shelf life. However, as a fresh strategy to bread staling, no extensive study has been conducted to evaluate its potential. The present study therefore examined the alhydwan as a comparison with Carboxymethylcellulose (CMC) at 0.5% (w/w) level in dough rheology improvement, microstructure, quality parameters and delayed wheat bread staling. The CMC or alhydwan for farinograph characteristics comprising the dough's portrayed showed greater water absorption, while growth and stability time was significantly decreased. Staling of bread, the findings showed that in both alhydwan and CMC minimized crumb hardening frequency and enhanced freshness, quality and retention ability for moisture, making the bread softer and postponed staling. The microstructure of CMC or alhydwan supplemented formulation showed the distinguishable characteristics and constituents that could explain, to some degree, that the CMC and alhydwan had antistaling effect. The incorporation of alhydwan such as CMC into the formulation of bread could thus play a sustainable role in improving the quality of bread by having an extended shelf life.

Involvement of tumor necrosis factor-α, interferon gamma-γ, and interleukins 1ß, 6, and 10 in immunosuppression due to long-term exposure to five common food preservatives in rats.

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)-1ß, 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-1ß, 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.

Immune-protective, antioxidant and relative genes expression impacts of ß-glucan against fipronil toxicity in Nile tilapia, Oreochromis niloticus.

Our study is considered to attempt reducing the immune-toxic and antioxidant impacts of exposure to fipronil (FP) on Nile tilapia, Oreochromis niloticus using the ß-glucan (ßG). Two hundred and seventy fingerlings of Nile tilapia were divided randomly into six groups (45 tilapias of each, in 3 replicates): group I control (CT) group nourished on a basal diet. Group II (ßG) nourished a basal diet supplemented with 0.4% ßG. Groups III (1/20 FP) and V (1/10 FP) was exposed to 1/20 and 1/10 of the 96 h LC50 of FP in water and nourished the basal diet respectively. Groups IV (1/20 FP+ ßG) and VI (1/10 FP+ ßG) were exposed to 1/20 and 1/10 FP concomitantly with 0.4% ßG supplementation for 90 successive days. Growth performance metrics were higher in ßG group than CT. While those metrics were fallen at exposure to 1/20 or 1/10 FP. Supplementation with ßG elevated the IgM and lysozyme levels.Whereas, tilapias exposed to FP only at different concentration showed lowering of those compared to CT. Supplementation with ßG was effectively augmented IgM and lysozyme in 1/20 FP exposed tilapias. Furthermore, in a minor grade at 1/10 FP exposed tilapias. Exposure to FP increased the activities of hepatic markers chiefly at 1/10, however the ßG supplementation was successfully improved these markers. There was imbalance of cortisol level at FP exposure where, ßG combining to FP alleviate this disparity. There was fallen in LDH, MDH and FDPase in ßG tilapias where continuing raise in 1/10 FP followed by 1/20 FP. ßG supplementation raise the level of GSH, without significant variations in MDA conversely occurs in FP alone. Genes expression of ßG caused raise of both GPx and GR, without fluctuations in CAT and SOD. Exposure to FP diminishes all evaluated antioxidant genes. It could fulfilled that supplementation with ßG successfully alleviated the immune-toxic and antioxidant impact of FP in tilapias.

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, TGFß-1, fibronectin, and caspase-3 genes.

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, TGFß-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.

Efficacy of Montanide (IMS 3015) as an adjuvant for an inactivated Rift Valley fever (RVF) vaccine in sheep.

This study was conducted to evaluate an adjuvant, Montanide (IMS 3015), in improving the quality of Rift Valley fever (RVF) vaccine relative to the traditional adjuvant, aluminum hydroxide gel. Vaccinated sheep were evaluated using biochemical analysis, kidney function tests, liver function tests, and immunological tests. Sheep vaccinated with Montanide (IMS 3015) adjuvant showed significantly higher total protein, total globulin, and gamma globulin concentrations from the second week until the fifth month than the controls. Conversely, albumin concentration and the A/G ratio significantly decreased during this period. Kidney function and liver function tests revealed no differences among any of the groups. There was a significant increase in lymphocyte proportion and a decrease in neutrophil proportion in sheep vaccinated with the Montanide (IMS 3015) adjuvant. Lymphocyte cell proliferation was significantly different in sheep vaccinated with the Montanide (IMS 3015) adjuvant from that in controls. Neutralizing indices were significantly higher in sheep vaccinated with the Montanide (IMS 3015) adjuvant than in controls. The current study showed that sheep vaccinated with inactivated RVF virus with Montanide (IMS 3015) as an adjuvant were protected and no pathological symptoms or biochemical changes were detected. Moreover, the vaccine induced rapid onset of immunological responses with long durations unlike inactivated RVF vaccine with aluminum hydroxide gel.

Moringa oleifera extract attenuates the CoCl2 induced hypoxia of rat's brain: Expression pattern of HIF-1α, NF-kB, MAO and EPO.

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl2) treatment in rats. The aim of this experiment was to explore the potential ameliorative potency of Moringa oleifera ethanolic extract (MO) against experimentally induced hypoxia on the structure and function of the rat's brain. Fifty male rats were allocated to five groups (10 rats each): a control group, a MO-treated group (400 mg/kg bw, orally), a CoCl2-treated group (40 mg/kg bw/day, orally), a prophylaxis group, and a therapeutic co-treated group. Oxidative stress biomarkers and monoamine neurotransmitter were evaluated in brain tissue. In addition, qRT-PCR for expression pattern of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. Glial fibrillary acidic protein (GFAP), apoptotic markers (BCL-2 and caspase 3) were detected immunohistochemically in brain cells. The results revealed a significantly lower concentration of GABA, monoamine neurotransmitter in hypoxic rat's brain. Moreover, an evident up-regulation of the mRNA expression of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. There was marked encephalopathy manifested by pyknotic neurons with eosinophilic cytoplasm, vacuolations and cerebral congestions in the hypoxic rat brains. Additionally, the score of neuronal expression occupied by GFAP- positive astroglia, Caspase-3 and microglial CD68 were elevated but Bcl-2 expression was found decreased in the hypoxic group than control. The endpoints of this study clearly stated that MO ethanolic extract suggestively counteracted neurotoxic impacts caused by hypoxia, particularly when it administered prior to and concurrently with CoCl2 administration.

Comparative haemato-immunotoxic impacts of long-term exposure to tartrazine and chlorophyll in rats.

The haemato-immunotoxic effects of the food colourants tartrazine and chlorophyll were evaluated. Thirty adult Sprague Dawley rats were distributed into three groups and orally administered water, tartrazine (1.35 mg/kg), or chlorophyll (1.35 mg/kg) daily for 90 days. Erythrogram and leukogram profiles were evaluated. The lysozyme, nitric oxide, phagocytic activity, and immunoglobulin levels were measured. Histological and immunohistochemical evaluations of splenic tissues were conducted. Changes in the interleukin (IL) 1ß, 6, and 10 mRNA expression levels were assessed. In the tartrazine-treated rats, a significant anaemic condition and marked leukocytosis were observed. Both the innate and humoural parameters were significantly depressed. Different pathological lesions were observed, including red pulp haemorrhages, vacuolation of some splenic cells, focal hyperplasia of the white pulp, and capsular and parenchymal fibrosis. A marked increase in vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (e-NOS) immunolabelling was evident. Marked upregulation of IL-1ß, IL-6, and IL-10 was recorded. In contrast, the chlorophyll-treated rats showed minimal haemato-immune responses. These results indicate that tartrazine exerts haematotoxic and immunotoxic effects following long-term exposure, whereas chlorophyll is a less hazardous food colourant.

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.

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.

Impact of subchronic exposure to triclosan and/or fluoride on estrogenic activity in immature female rats: The expression pattern of calbindin-D9k and estrogen receptor α genes.

This study explored the influence of triclosan (TCS) in the absence and presence of sodium fluoride (NaF) on estrogenic activity and thyroid function of adolescent female rats. The results indicated that the individual exposure to TCS evoked a significant decline in T3 and T4 but the levels of estradiol, FSH, and LH were significantly elevated beside marked up regulation of calbindin-D9k and estrogen α mRNA expression. On the other hand, the single exposure to NaF causes insignificant changes in thyroid hormones, but evoked a trend toward an increase in both estradiol and LH levels. No significant differences in the TSH level were recorded among the experimental groups. The joint exposure to TCS and NaF induced a significant improvement in thyroid and reproductive hormone levels. Overall, these findings revealed that exposure to TCS resulted in significant endocrine and reproductive alterations in immature female rats, while TCS + NaF coexposure resulted in lessening most effects.

Querectin Alleviates Zinc Oxide Nanoreprotoxicity in Male Albino Rats.

Zinc oxide nanopartciles (ZnONPs) involved in advanced technologies, and their wide-scale use in consumer market makes human beings more prone to the exposure to ZnONPs. The present study was undertaken to evaluate amelioration of ZnONP-induced toxicities with querectin in male albino rats. ZnONPs-treated rats showed a significant decrease in sperm cell count, sperm motility, live and normal sperms, as well as serum testosterone level. Severe histopathological damage with a significant increase in lipid peroxidation and a decrease in antioxidant enzymes activity and the GSH level were observed in the affected testis. Relative quantitative polymerase chain reaction results showed a significant decrease in antioxidant enzymes (superoxide dismutase and catalase) and a significant decrease in 3ß-HSD, 17ß-HSD, and Nr5A1 transcripts. Rats-administered querectin along with ZnONPs showed less toxic effects on all studied reproductive traits and mRNA transcripts. Our results suggest that querectin is beneficial for preventing or ameliorating ZnONP reproductive toxicities in males.

Ameliorative effects of phycocyanin against gibberellic acid induced hepatotoxicity.

Gibberellic acid (GA3) was used extensively unaware in agriculture in spite of its dangerous effects on human health. The current study was designed to investigate the ameliorative effects of the co-administration of phycocyanin with GA3 induced oxidative stress and histopathological changes in the liver. Forty male albino rats were randomly divided into four groups. Group I (control group) received normal saline for 6 weeks, Group II (GA3 treated group) received 3.85 mg/kg body weight GA3 once daily for 6 weeks, Group III (phycocyanin treated group) received Phycocyanin 200 mg/kg body weight/day for 6 weeks orally dissolved in distilled water and Group IV was treated with GA3 and phycocyanin at the same doses as groups 2 and 3. All treatments were given daily using intra-gastric intubation and continued for 6 weeks. Our results revealed significant downregulation of antioxidant enzyme activities and their mRNA levels (CAT, GPx and Cu-Zn, SOD) with marked elevation of liver enzymes and extensive fibrous connective tissue deposition with large biliary cells in hepatic tissue of GA3 treated rats, while treatment with phycocyanin improved the antioxidant defense system, liver enzymes and structural hepatocytes recovery in phycocyanin treated group with GA3. These data confirm the antioxidant potential of Phycocyanin and provide strong evidence to support the co-administration of Phycocyanin during using GA3.

Molecular mechanisms of anti-hyperglycemic effects of Costus speciosus extract in streptozotocin-induced diabetic rats.

OBJECTIVES: To investigate the mechanisms of the anti-hyperglycemic effect of Costus speciosus (C. speciosus) root ethanolic extracts (CSREt) by assessing its action on insulin synthesis and glucose catabolic enzyme gene expression and activities in streptozotocin (STZ) diabetic rats. METHODS: This study was carried out at the Biochemical Laboratory, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt between July and August 2013. Sixty male albino rats (120 +/- 20 g weight, and 6 months old) were used and divided into 6 groups (n=10). Two groups served as diabetic and nondiabetic controls. Four groups of STZ diabetic animals were given oral C. speciosus (CSREt) in doses of 200, 400, and 600 mg/kg body weight, and 600 µg/kg body weight of the standard drug glibenclamide for 4 weeks. RESULTS: The CSREt 400 and 600 mg/kg body weight induced a decrease in blood glucose and an increase in serum insulin level, glucokinase (GK), aldolase, pyruvate kinase (PK), succinate dehydrogenase (SDH), and glycogen synthase activities  in addition to a higher expression level of insulin, insulin receptor A (IRA), GK, PK, SDH, and glucose transporting protein. CONCLUSION: The C. speciosus has anti-hyperglycemic activity. It induces insulin secretion and release from cells, as well as stimulates the tissue's insulin sensitivity leading to an increase of the tissues' glucose uptake, storage, and oxidation.