Effect of perinatal dietary protein deficiency on some neurochemicals and cytoarchitectural balance, in F1 and F2 generations of rats.

ABSTRACTProtein deficiency, characterized by an inadequate intake of protein in the diet that fails to meet the body's physiological requirements across various stages, can lead to detrimental outcomes. This is of interest due to the persistent low protein content in staple foods and suboptimal dietary patterns. The study sought to assess the intergenerational repercussions of dietary protein deficiency on specific neurochemicals and the cytoarchitecture of the brain within the F1 and F2 generations of rats. The rats were categorized into four groups based on the protein content percentage in their diets: 21% protein diet (21%PD), 10% protein diet (10%PD), 5% protein diet (5%PD), and control diet. Neurobehavior was assessed, while brain serotonin and dopamine levels were measured using HPLC. BDNF and GDNF expression in the hippocampal and prefrontal (PFC) sections, Immunohistochemical investigations of the morphological impact on the hippocampus and PFC, were also analyzed. The protein-deficient groups displayed anxiety, loss of striatal serotonin and increased dopamine levels, degenerated pyramidal cells in the hippocampus, and a prominent reduction in cellular density in the PFC. BDNF and GDNF levels in the PFC were reduced in the 5%PD group. GFAP astrocyte expression was observed to be increased in the prefrontal cortex (PFC) and hippocampal sections, indicating heightened reactivity. The density of hypertrophied cells across generations further suggests the presence of neuroinflammation. Changes in brain structure, neurotransmitter levels, and neurotrophic factor levels may indicate intergenerational alterations in critical regions, potentially serving as indicators of the brain's adaptive response to address protein deficiency across successive generations.

P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis.

OBJECTIVE: With increasing incidence of cancers globally and limited resources in some affected countries, repurposing existing drugs for reducing tumorigenesis is highly important. Artemisinin and caffeine have potent anti-oxidative and anti-tumor properties but are therapies for other diseases. This study evaluated the biochemical and p53 gene modulatory effects of doses of artemisinin-caffeine combination on breast, lungs and liver tissues in rats induced with DMBA. METHODS: After due ethical approval, 30 animals were treated with 40mg/kg single dose of 7,12-dimethylbenzene anthracene (DMBA) as a model for DNA damage and induction of carcinogenesis. Five animals each received normal saline (normal), low dose artemisinin (Art; 4mg/kg), low dose caffeine (Caff; 25mg/kg), low dose combination of caff + art (25+4mg/kg), high dose combination of caff + art (50+8mg/kg) or no treatment (DMBA). All treatment doses were orally administered daily for two weeks post DMBA treatment. Nitric oxide levels and p53 relative gene expression was carried out using primer-specific RT-PCR, GAPDH was used as loading control and amplicons were resolved by gel electrophoresis. RESULTS: DMBA induced lesions in breast, liver, and lung tissues evident from histology analysis, compared to normal group. In all 3 tissues, caffeine (25mg/kg) and combination of caff + art (25+4mg/kg) significantly reduced p53 gene expression (p < 0.05), but there was significant increase in the group treated with low dose art (4mg/kg) and high dose caff + art, which were similar to DMBA group (p<0.05). In lungs, nitric oxide (NO) increased in all groups but not in caffeine, in the liver NO decreased with caffeine or its combination with art, compared to DMBA group. CONCLUSIONS: This study shows a dose-dependent synergistic anticancer effects of caffeine and artemisinin combination on p53 gene and nitric oxide regulation hence can mitigate tumor development.

Effects of chronic exposure to paint fumes among artisans in Lagos State, Nigeria.

The chronic effects of automobile paint fumes and their volatile organic constituents form detrimental air pollution with hazardous consequences especially to paint industrial workers and the population within the vicinity. This study investigated the chronic effects of exposure to paint fumes in Mushin area of Lagos, Nigeria. Fifty artisans employed in automobile painting industries were compared with 50 control group whose work does not expose them to paint fumes. Five milliliters blood was collected and used for assessment of hematological and biochemical parameters. This was compared in artisan and unexposed control group and p value of < 0.05 indicates significant difference. In artisans, kidney function analysis showed a significant decrease in potassium (3.63 ± 0.1012 mEq/L) compared to healthy control (4.26 ± 0.1699 mEq/L, p = 0.0049), as well as bicarbonate ion concentration (23.89 ± 0.3795 vs 26.40 ± 0.3578 mmol/L respectively, p = 0.0011), however, a significant increase in creatinine level was recorded in artisans than control group (1.140 ± 0.1075 vs 0.76 ± 0.03578 mg/dL, p = 0.03); which is an indicator of renal function impairment. AST and ALT levels were significantly higher in artisans (11.44 ± 0.8190 and 8.78 ± 0.7558 U/L) compared to control group (6.83 ± 0.3086 and 6.67 ± 0.3354 U/L), respectively (p < 0.05), while ALP levels were similar. For oxidative stress parameters - CAT, MDA and protein, there was a significant increase in artisans while the corresponding GSH and SOD activities decreased significantly (p < 0.05). The results showed similar Zinc and Chromium levels in both groups but Lead was not detected in any participant. The findings of this study indicate that chronic exposure to paint fumes among automobile painting artisans may impair renal function, liver function and induce oxidative damages. Creating awareness of potential dangers and recommending use of personal protective equipment among automobile painting artisans can further decrease their exposure.ga1.

Haemoglobin oxygen saturation, leucocyte count and lactate dehydrogenase are predictors of elevated cerebral blood flow velocity in Nigerian children with sickle cell anaemia.

BACKGROUND: Transcranial Doppler ultrasound (TCD) scan, which measures blood flow velocity through the time-averaged mean of maximum velocities (TAMMVs) in the internal carotid arteries and middle cerebral arteries, is a useful screening tool for predicting stroke risk in children with sickle cell anaemia (SCA). AIM: To investigate which clinical and laboratory indices predict abnormal TCD velocity in children with SCA. METHODS: Fifty-four SCA patients with normal TCD (TAMMV < 170 cm/s), classified as negative TCD (NTCD), and 93 patients with conditional and abnormal TCD velocities (TAMMV ≥ 170 cm/s) classified as positive TCD were recruited. The haemoglobin oxygen saturation, haematological variables, nitric oxide metabolites and lactate dehydrogenase activity of the patients were analysed. RESULTS: The mean (SD) age was 7.16 (3.84) years (range 2-16). The median SpO2 of the patients in the positive TCD group was significantly lower than that of the negative TCD group (p = 0.002). Multivariate logistic regression analysis indicated that the MCV [odds ratio (OR) 1.12, 95% confidence interval (CI) 1.04-1.22, p = 0.01)], MCH (OR 1.34, 95% CI 1.02-1.77, p = 0.04), leucocyte count (OR 1.26, 95% CI 1.07-1.49, p = 0.01) and lactate dehydrogenase (LDH) level (OR 1.00, 95% CI 1.00-1.01, p = 0.01) were independent predictors of high cerebral blood flow velocities. CONCLUSIONS: These clinical and laboratory indices are characteristic of chronic hypoxia and severe anaemia and are predictors of abnormal cerebral blood flow velocity. They can be used to predict stroke risk in children with SCA when access to TCD screening is limited.

Phytomedicines and nutraceuticals: alternative therapeutics for sickle cell anemia.

Sickle cell anemia is a genetically inherited disease in which the "SS" individual possesses an abnormal beta globin gene. A single base substitution in the gene encoding the human ß -globin subunit results in replacement of ß 6 glutamic acid by valine, leading to the devastating clinical manifestations of sickle cell disease. This substitution causes drastic reduction in the solubility of sickle cell hemoglobin (HbS) when deoxygenated. Under these conditions, the HbS molecules polymerize to form long crystalline intracellular mass of fibers which are responsible for the deformation of the biconcave disc shaped erythrocyte into a sickle shape. First-line clinical management of sickle cell anemia include, use of hydroxyurea, folic acid, amino acids supplementation, penicillinprophylaxis, and antimalarial prophylaxis to manage the condition and blood transfusions to stabilize the patient's hemoglobin level. These are quite expensive and have attendant risk factors. However, a bright ray of hope involving research into antisickling properties of medicinal plants has been rewarding. This alternative therapy using phytomedicines has proven to not only reduce crisis but also reverse sickling (in vitro). The immense benefits of phytomedicines and nutraceuticals used in the management of sickle cell anemia are discussed in this paper.