Alkaline-extracted cyanide from cassava wastewater and its sole induction of chromosomal aberrations in Allium cepa L. root tips.

Cassava, a staple crop in Nigeria, processed by numerous factories in rural and suburban locations is known to contain some level of cyano compounds. Lack of stringent environmental regulations on the management of cassava wastewater (CWW) from cassava-processing factories had led to its indiscriminate discharge on the environment. CWW samples were obtained from cassava-processing factories from selected states (Lagos (A), Oyo (B), Ogun 1 (C1), Ogun 2 (C2) and Cross River (D)) in Nigeria to determine the cytotoxic and genotoxic effects of extracted cyanide from the wastewaters. The cyanide was hydrolysed via chemical degradation utilizing 1.25 M NaOH and subsequently titrated using silver nitrate with p-dimethylaminobenzalrhodamine as indicator. Further, in order to explore the potential toxicity of this pollutant present in the effluent, a battery of short-term biological assay (Allium cepa chromosomal aberration test) was used. Bulbs with roots of Allium cepa L. were treated with different concentrations (0.05%, 0.1%, 0.2%, 0.4% and 0.8%) of CWW, and after 48 h, the root tips were processed for cytological studies by the aceto-orcein squash procedure. The results revealed that cyanide concentrations on re-fluxing were in the range of 1.0 and 1.3 mg/L. All concentrations induced a number of chromosomal aberrations in the root tip cells. The mitotic index decreased significantly (p < 0.05) with increasing concentration. The cytotoxic effects showed strong concentration-dependent root growth inhibition with EC50 values of 30%, 20%, 37%, 43% and 22% for A, B, C1, C2 and D, after 72 h. The findings thus indicate that alkali treatment is very efficient in degrading the cyanide content of CWW and has shown that the combination of physico-chemical analysis along with the sole toxicity assessment could provide valuable information about the sole toxicity of cyanide as a chemical pollutant present in the cassava effluent.

Molecular mechanism of mitoquinol mesylate in mitigating the progression of hepatocellular carcinoma-in silico and in vivo studies.

The safety and efficacy of mitoquinol mesylate (MitoQ) in attenuating the progression of hepatocellular carcinoma (HCC) in Wistar rats has been reported. However, the binding modes for MitoQ as well as its molecular mechanisms in cirrhosis and liver cancer have not been fully investigated. This study sought to understand the structural and molecular mechanisms of MitoQ in modulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and mitochondrial succinate dehydrogenase (SDH) in cirrhotic-HCC rats. The research indicates that the upregulated Nrf2 expression in cirrhotic-HCC rats was significantly (p < 0.05) reduced by MitoQ while the activity of SDH was significantly (p < 0.05) increased. Analysis of binding modes revealed MitoQ interacts with amino acid residues in the active pocket of tramtrack and bric-a-brac (BTB) and KELCH domains of KEAP1 with average binding affinities of -66.46 and -74.74 kcal/mol, respectively. Also, MitoQ interacted with the key amino acid residues at the active site of mitochondrial complex II with a higher average binding affinity of -75.76 kcal/mol compared to co-crystallized ligand of complex II (-62.31 kcal/mol). Molecular dynamics simulations data showed the binding of MitoQ to be stable with low eigenvalues while the quantum mechanics calculations suggest MitoQ to be very reactive with its mechanism of chemical reactivity to be via electrophilic reactions. Thus, MitoQ modulates expression of Nrf2 and enhances activity of mitochondrial SDH in cirrhotic-HCC rats via its interaction with key amino acid residues in the active pocket of BTB and KELCH domains of KEAP1 as well as amino residues at the active site of SDH. These findings are significant in demonstrating the potential of Nrf2 and SDH as possible biomarkers for the diagnosis and/or prognosis of hepatocellular carcinoma in patients. This study also supports repurposing of mitoQ for the treatment/management of liver cirrhosis and HCC.

Aberrant effect of genistein on placenta development expressed through alteration in transforming growth factor-ß1 and alkaline phosphatase across the maternal serum, the placenta and the amniotic fluid.

OBJECTIVES: The mechanism via which genistein, the major isoflavone content of soya, adversely influenced placenta and fetal development was evaluated in pregnant laboratory rats. MATERIALS AND METHODS: There were control, 2 mg/kg and 4 mg/kg genistein groups of rats with five sub-groups based on gestation termination day. At the end of the experiment, animals were sacrificed by CO2 and cervical dislocation, while plasma and serum were processed and stored. The abdomen was opened and the amniotic fluid was siphoned from the uterine sacs, processed and stored. The embryonic implants were excised, the placenta was separated from the fetus and weighed separately. Placenta homogenate was prepared from the harvested placenta, while the rest were processed for histological studies. Transforming growth factor (TGf-ß1) and alkaline phosphatase (ALP) were assayed for in all samples. A significant decrease in the placenta and fetal weights, and a significant decrease in serum and placenta homogenate ALP levels were recorded in genistein groups. RESULTS: There was a reduction in the Trophoblast giant cells population (TGCs). TGCs zone depth, perimeter, and an increase in the placenta and amniotic fluid's TGf-ß1 in all genistein groups at GD-13 towards term, and GD-18 and GD-20, respectively. Maternal plasma TGf-ß1 was increased in 2 mg group early in pregnancy while its level significantly decreased in both 2 mg and 4 mg genistein groups at mid-gestation towards GD-19. CONCLUSION: Genistein aberrant effect on fetal development was via its adverse effect on TGCs proliferation and TGf-ß1 activities in the placenta tissue.

Modulatory role of genistein on placenta and maternal bone minerals composition: further insight into its influence on pregnancy and foetal development.

Pregnancy is a crucial period with an increased need to supply necessary minerals for both the mother and the developing foetus and with a tendency of altering the maternal bone mineral density when there is no balance between demand and supply of these minerals. This study evaluated the influence of genistein on the maternal bone and placenta mineral composition. Pregnant rats were grouped into control, 2 mg/kg and 4 mg/kg genistein groups, dosed accordingly till sacrificed at different gestation days (GD). Body and placenta weights, right femur bone and placenta mineral composition were analysed. A significant decrease in body weight and percentage relative right femur bone weight at GD-20 was recorded in the 2-mg group with the reverse occurring in the 4-mg genistein group. The right femur bone Ca2+ and Zn2+ was reduced towards GD-20 in both 2-mg and 4-mg genistein groups. Genistein had no influence on placenta selenium and cadmium level, but significantly decreased zinc and lead level concentration as the gestation progressed towards GD-20. Copper level was increased at GD-16 at the doses used. Genistein modulated maternal bone mineral composition and placenta capability in retaining some heavy metals at various stages of pregnancy.

High-Dose Perinatal Folic-Acid Supplementation Alters Insulin Sensitivity in Sprague-Dawley Rats and Diminishes the Expression of Adiponectin.

The possible intake of folate in excess of the recommended upper levels is a matter of critical importance. This study was conducted to investigate the effects of prenatal and postnatal high folic acid supplementation (FAS) on glucose tolerance, insulin sensitivity, lipid metabolism, and expression of adiponectin in rats. The study included 20 female rats divided into two groups: control group and FAS group (receiving high folic acid supplemented diet). Both groups of female rats were mated and pregnancy confirmed. At parturition, the diet of 5 dams that were fed with control diet during gestation and their litters was changed to FAS diet and continued throughout lactation. Similarly, half of the dams that were previously fed with FAS diet during gestation and their litters were also changed to control diet. The remaining 5 dams in each group continued on their respective diets throughout lactation with their litters. Other dams remained on their respective diets throughout lactation. Food and water intake, body weight, lipid concentrations, insulin, and the expression of adiponectin were determined. Glucose tolerance and insulin sensitivity were also measured to evaluate glucose homeostasis. FAS significantly increased the postweaning food, water intake, triglyceride, and insulin levels but diminished insulin sensitivity in adult offspring. The expression of adiponectin in insulin-sensitive tissues was also significantly decreased and these were consistent with insulin resistance of FAS offspring. High-dose FAS may promote insulin resistance and dyslipidemia and disrupt glucose metabolism possibly by depressing adiponectin expression. Although this is an animal model and the effects of the diets cannot be directly transposed to humans, this study provides indications of the possible adverse effects of FAS maternal diet on glucose metabolism in the offspring.

Adverse effects of noise stress on glucose homeostasis and insulin resistance in Sprague-Dawley rats.

Noise pollution remains a pervasive health hazard that people encounter especially in large commercial metropolis and has been implicated in many adverse non-auditory health conditions such as hypertension, atherosclerosis, vascular (endothelial) dysfunction and metabolic disorders. There is a growing body of evidence showing that chronic noise exposure is associated with an increased risk of hypercholesterol, adiposity and development of type 2 diabetes. The present study investigated the effect of noise stress on parameters of glucose homeostasis in male rats and possible recovery after noise cessation. Twenty-four (24) adult male Sprague-Dawley rats were designated into four groups (n = 6 per group). All rats except the control group were exposed to 95dB noise using a noise generator for 28 consecutive days. A group of rats was investigated immediately after 28 days of noise exposure (NE28), while others were left to recover from noise stress for 7 days (NER7) or 14 days (NER14). OGTT and ITT were performed using standard methods. Plasma levels of triglyceride (TRIG), total cholesterol (CHOL), low density lipoprotein (LDL) and high-density lipoprotein (HDL) were determined. Serum level of insulin, corticosterone (CORT) and corticosterone-releasing-factor (CRF) were determined using ELISA. Homeostasis model assessment-insulin resistance (HOMA-IR) and glycogen content in liver as well as gastrocnemius muscle were also determined. Although glucose tolerance remained unchanged in the noise-exposed groups, insulin sensitivity was however significantly reduced compared with control. There was significant increase (P < 0.05) in the level of CHOL, LDL and HDL. Noise also increased (P < 0.05) both insulin and CORT levels; and elicited a higher HOMA-IR index in NE28 rats. Hepatic and myocytic glycogen content were lower (P < 0.05) in NE28 rats relative to control. The reported changes above were reversed following a 14-day noise withdrawal period. Noise-induced insulin resistance may result from dysregulation of the stress axis and appears to be reversible with noise cessation.

Magnesium upregulates insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide-induced type-2 diabetic rats.

OBJECTIVE: We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. METHODS: Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile, malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured, and insulin resistance index was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: Magnesium supplementation improved glucose tolerance and lowered blood glucose levels almost to the normal range. We also recorded a noticeable increase in insulin sensitivity in Mg-D groups when compared with DU rats. Lipid perturbations associated T2D were significantly attenuated by magnesium supplementation. Fasting glucose level was comparable to control values in the Mg-D groups while the HOMA-IR index was significantly lower compared with the DU rats. Magnesium reduced MDA but increased glutathione concentrations compared with DU group. Moreover, INSR and GLUT4 levels were elevated following magnesium supplementation in T2D rats. CONCLUSION: These findings demonstrate that magnesium may mediate effective metabolic control by stimulating the antioxidant defense, and increased levels of INSR and GLUT4 in diabetic rats.