An Update Overview on Mechanistic Data and Biomarker Levels in Cobalt and Chromium-Induced Neurodegenerative Diseases.

There is increasing evidence that the imbalance of metals as cobalt (Co) and chromium (Cr) may increase the risk of development and progression of neurodegenerative diseases (NDDs). The human exposure to Co and Cr is derived mostly from industry, orthopedic implants, and polluted environments. Neurological effects of Co and Cr include memory deficit, olfactory dysfunction, spatial disorientation, motor neuron disease, and brain cancer. Mechanisms of Co and Cr neurotoxicity included DNA damage and genomic instability, epigenetic changes, mitochondrial disturbance, lipid peroxidation, oxidative stress, inflammation, and apoptosis. This paper seeks to overview the Co and Cr sources, the mechanisms by which these metals induce NDDs, and their levels in fluids of the general population and patients affected by NDDs. To this end, evidence of Co and Cr unbalance in the human body, mechanistic data, and neurological symptoms were collected using in vivo mammalian studies and human samples.

Multi-Organ inducedtoxicity of metal mixture (CdCl2, HgCl2, Pb(NO3)), and the ameliorative potentials of plantain Musa paradisiaca (F. Musaceae) stem juice on male Wistar rats.

Industrialization and urbanization have caused a hike in all forms of emissions, many of which have detrimental effects on plants, animals, the environment, and worse still, humans. In a quest for novel products (household, and medical), manufacturing industries work tirelessly worldwide using metals to meet man's needs. However, such metals especially those confined to this research (Hg, Cd, and Pb) are inherently hazardous to not just the environment but human life and existence. Thirty (30) male Wistar rats divided into six groups of five rats each was used for the study. Stock solutions of the heavy metals were prepared and the required dose calculated according to individual weight and administered as such to group 2-5, plantain stem juice (PSJ) was administered to groups 3 to 5 in increasing dose after receiving the HMM (heavy metal mixture) while group six received medium-dose of PSJ used in the study only. Bodyweight of the rats was monitored once in three weeks while the feed and fluid intake were monitored thrice a week. At the end of the ninth week, the animals were weighed and sacrificed. Organs of interest (brain, heart, lungs, and thymus) were harvested and analyzed. Analysis done include Histopathology, hematological, biochemical, and organs/blood metal concentration. The results obtained showed a decline in the weight of animals that received metal mixture only when compared to normal control and PSJ treated groups. This could be traceable to the decline in feed intake of the metal-induced groups. However, no significant effect was observed in the histology of the Thymus and cerebellum even though the presence of a vacuole in the cerebral cortex indicated an anomaly. The histology of the heart and the lungs showed some level of distortion which was ameliorated dose-dependently with the administration of PSJ. Interestingly, after a decrease in the antioxidant level upon administration of metal mixture, a booster effect was observed with an increasing dose of PSJ. In conclusion, the recent findings have demonstrated that treatment with PSJ in HMM induced intoxication has a significant role in protecting the animals from all possible organ toxicity by modulating hemato-biochemical parameters and oxidative stress level.

Mechanistic considerations and biomarkers level in nickel-induced neurodegenerative diseases: An updated systematic review.

The environment has been implicated to be a strong determinant of brain health with higher risk of neurodegeneration. The drastic rise in the prevalence of neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), multiple sclerosis (MS) etc., supports the idea that environmental factors may play a major role in NDDs aetiology. Nickel is one of the listed environmental metals reported to pose a serious threat to human health. This paper reported available studies on nickel level in NDDs covering both animal and human studies. Different databases were searched for articles reporting the main neurotoxicity mechanisms and the concentration of nickel in fluids and tissues of NDDs patients compared to controls. Data were extracted and synthesized by ensuring the articles were related to nickel and NDDs. Various mechanisms were reported as oxidative stress, disturbances in mitochondrial membrane potential, trace elements homeostasis destabilization, etc. Nickel was found elevated in biological fluids as blood, serum/plasma and CSF and in the brain of NDDs, as a consequence of unintentional exposure thorough nickel-contaminated air, food, water, and skin contact. In addition, after exposure to nickel, the concentration of markers of lipid peroxidation were increased, while some antioxidant defence systems decreased. Thus, the reduction in the exposure to nickel contaminant may hold a promise in reducing the incidence of NDDs.

Modulation of Estrogen α and Progesterone Receptors in Triple Negative Breast Cancer Cell Lines: The Effects of Vorinostat and Indole-3-Carbinol In Vitro.

BACKGROUND/AIM: Triple negative cancer (TNBC) is a subtype of breast cancer that is highly aggressive, with poor prognosis and responds differently to treatments. This study investigated the role of vorinostat and indole-3-carbinol (I3C) on regulating critical receptors that are not normally expressed in TNBC. MATERIALS AND METHODS: Using real-time PCR, immunostaining, and western blots, the re-expression of estrogen receptor α (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) receptors was examined in four different TNBC cell types. RESULTS: ERα was re-expressed in three subtypes using vorinostat and I3C. Re-expression of the PR by vorinostat was also detected. Neither vorinostat nor I3C resulted in re-expression of the HER2 receptor. A significant decrease in growth and sensitivity to tamoxifen was also noted. CONCLUSION: The results of this study show that vorinostat and I3C modulate the re-expression of critical receptors in certain subtypes of TNBC through several pathways and these effects can be influenced by the molecular profiles of TNBCs.

Morphological changes in the pancreas and glucose reduction of the aqueous extract of Costus afer leaf on alloxan-induced diabetic rats.

BACKGROUND: Considering the antihyperglycemic and antioxidant activities of herbs, this study has evaluated the morphological changes, hypoglycemic effect, and comparative ameliorating effects of Costus afer Ker Gawl leaf and glibenclamide on pancreatic injury induced by alloxan. METHODS: Thirty adult male albino rats that were divided into six groups of five weight-matched animals each were used in the study. Groups 1 and 2 served as controls, whereas groups 3-6 were alloxan-induced diabetic groups treated with different doses of the extract (375, 750, and 1125 mg/kg C. afer) and glibenclamide, respectively. The glucose level was measured daily, whereas the weight of the animal was monitored on a weekly basis for 21 days. The oral glucose tolerance test was measured on overnight fasted rats after glucose load at 0, 30, 60, 90, and 120 min. The histopathology of the pancreas was also investigated. RESULTS: The phytoconstituents of C. afer Ker Gawl leaves include glycosides, tannins, saponins, terpenoid, phenolic compound, flavonoids, and alkaloids. Costus afer possessed significant hypoglycemic (p<0.05) effect and reversed the histopathologic damage of pancreases in alloxan-induced diabetic rats comparable to those of glibenclamide. CONCLUSIONS: Costus afer leaves possess both antidiabetic and tissue protective properties on pancreases of investigated rats.

Cytological and biochemical studies during the progression of alloxan-induced diabetes and possible protection of an aqueous leaf extract of Costus afer.

Some plants have proven efficacy in the management of diabetes mellitus, of which Costus afer is one. This study was designed to evaluate the cytological and biochemical properties, and comparative ameliorating effects, of an aqueous extract of Costus afer Ker Gawl. (Costaceae) leaf and glibenclamide (GBM), in liver, kidney, and pancreatic injury induced by alloxan. Thirty male albino rats were divided into six weight-matched groups. Group one served as the negative control (non-induced and non-treated, control), while groups 2-6 were alloxan-induced diabetic groups. Group 2 served as a positive control (induced and non-treated, IC), groups 3-5 were treated with different doses of the extract (375, 750, and 1,125 mg/kg body weight) and glibenclamide, respectively. Body weight, absolute and relative organ weights, food and fluid intake, levels of serum glucose and liver enzymes and kidney parameters were calculated and compared. Hepatocytes, renal tubules, and pancreatic cells of diabetic rats, in diabetic non-treated and treated rats were harvested and examined histopathologically. There was dose dependent amelioration on the injuries induced by alloxan on both hepatocytes, renal tubules, and pancreatic cells after treatment with Costus afer. The glucose level was reduced significantly in the Costus afer treated diabetic rats compared with the non-treated diabetic group. Costus afer leaves seem to be effective against diabetic cell injury induced in rat liver, kidney, and pancreas.

Costus afer ker gawl leaves against gentamicin-induced nephrotoxicity in rats.

INTRODUCTION: The nephroprotective effect of the aqueous extract of Costus afer leaves was evaluated in male albino Wistar rats with gentamicin-induced kidney injury. MATERIALS AND METHODS: In a 2-phase study, 30 weight-matched male Albino Wistar rats were divided into 6 groups of 5 animals to receive gentamicin, 90 mg/kg/d (except for the control group) for 7 days in the first phase to induce kidney injury. The second phase was treatment of rats with 375 mg/kg, 750 mg/kg, and 1125 mg/kg of aqueous extract of Costus afer leaves. One group received Silymarin only. Body weight, daily fluid and feed intakes, and serum levels of creatinine, urea, and electrolytes were monitored on a weekly basis, and renal histology was evaluated at the end of the study. RESULTS: The aqueous extract of Costus afer significantly increased the feed intake and fluid intake in a dose dependent manner when compared with the gentamicin-treated group. Low and medium doses of the extract reversed the deleterious effect of gentamicin on the kidney. The extract also significantly decreased the absolute kidney weight and relative kidney weight when compared with the corresponding weights in the gentamicin-treated group. Costus afer significantly decreased serum sodium, blood urea, and serum creatinine levels and significantly increased serum potassium level in gentamicin-induced nephrotoxic rats. CONCLUSIONS: Aqueous extract of Costus afer leaves may attenuate gentamicin-induced nephrotoxicity in rats.