Adverse cardiovascular effects of exposure to cadmium and mercury alone and in combination on the cardiac tissue and aorta of Sprague-Dawley rats.

The aim of this study was to identify cardiovascular effects of relevant concentrations of Cd and Hg alone and in combination as a mixture in water. This was achieved by administering to male Sprague-Dawley rats via gavage 0.62 mg/kg Cd or 1.23 mg/kg Hg, or a combination of 0.62 mg/kg Cd and 1.23 mg/kg Hg in the co-exposure group for 28 days. Concentrations were the rat equivalence dosages of 1,000 times the World Health Organization's limits of 0.003 mg/L and 0.006 mg/L for Cd and Hg, respectively, for water. With termination, blood levels of the metals were increased. For all metal exposed groups, histological evaluation and transmission electron microscopy of the myocardium revealed myofibrillar necrosis, increased fibrosis, vacuole formation and mitochondrial damage. Cd caused the most mitochondrial damage while Hg to a greater degree induced fibrosis. In the aorta, both Cd and Hg also increased collagen deposition adversely altering the morphology of the fenestrated elastic fibers in the tunica media. Co-exposure resulted in increased cardiotoxicity with increased mitochondrial damage, fibrosis and distortion of the aortic wall as a result of increased collagen deposition, as well as altered elastin deposition, fragmentation and interlink formation. These are typical features of oxidative damage that correlates with a phenotype of premature ageing of the CVS that potentially can lead to hypertension and premature cardiac failure.

Ovulation mitigates fatty liver associated with reproductive suppression and oxidative stress in Damaraland mole-rats (Fukomys damarensis).

Oxidative damage is often linked to reproduction; however, reproducing female Damaraland mole-rats (Fukomys damarensis) exhibit a reduction in oxidative damage relative to their non-reproductive, anovulatory, cohorts. Specifically, liver concentrations of malondialdehyde, a biomarker for lipid peroxidation, are significantly lower in reproducing females. We examined liver histology in reproductive, anovulatory and recently ovulating non-reproductive females, demonstrating an accumulation of lipid droplets only in the livers of anovulatory females and no fibrosis, cell death or inflammatory infiltrates in any group. Our observations suggest that anovulatory females experience a form of non-alcoholic fatty liver disease, which is reversed once they commence ovulation. We propose hormonal interactions that may underlie our observations.

Oral exposure to cadmium and mercury alone and in combination causes damage to the lung tissue of Sprague-Dawley rats.

Environmental presence and human exposure to heavy metals in air and cigarette smoke has led to a worldwide increase in respiratory disease. The effects of oral exposure to heavy metals in liver and kidney structure and function have been widely investigated and the respiratory system as a target is often overlooked. The aim of the study was to investigate the possible structural changes in the lung tissue of Sprague-Dawley rats after oral exposure for 28 days to cadmium (Cd) and mercury (Hg), alone and in combination at 1000 times the World Health Organization's limit for each metal in drinking water. Following exposure, the general morphology of the bronchiole and lungs as well as collagen and elastin distribution was evaluated using histological techniques and transmission electron microscopy. In the lungs, structural changes to the alveoli included collapsed alveolar spaces, presence of inflammatory cells and thickening of the alveolar walls. In addition, exposure to Cd and Hg caused degeneration of the alveolar structures resulting in confluent alveoli. Changes in bronchiole morphology included an increase in smooth muscle mass with luminal epithelium degeneration, detachment and aggregation. Prominent bronchiole-associated lymphoid tissue was present in the group exposed to Cd and Hg. Ultrastructural examination confirmed the presence of fibrosis where in the Cd exposed group, collagen fibrils arrangement was dense, while in the Hg exposed group, additional prominent elastin was present. This study identified the lungs as target of heavy metals toxicity following oral exposure resulting in cellular damage, inflammation and fibrosis and increased risk of respiratory disease where Hg showed the greatest fibrotic effect, which was further, aggravated in combination with Cd.

Beneficial effects of folic acid on the kidneys and testes of adult albino rats after exposure to methomyl.

The aim of this study was to evaluate the protective effect of folate against methomyl-induced toxicity on the kidneys and testes of male rats. Adult male albino rats were divided into four groups; Group I served as the control (vehicle), Group II received folic acid (1.1 mg per kg b.wt.), Group III methomyl (1 mg per kg b.wt.) and Group IV folic acid and methomyl. Treatments were administered via oral gavage on a daily basis for 14 weeks. Thereafter blood samples were collected and serum creatinine, testosterone and total antioxidant capacity (TAC) were determined. Animals were sacrificed and semen analysis was conducted. The kidneys and testes were excised and malondialdehyde (MDA) levels were determined. Histopathological and immunohistochemical analyses for caspase-3 were also undertaken. Methomyl treatment resulted in a significant (p < 0.001) elevation of creatinine and MDA levels and significant (p < 0.001) reduction in testosterone and TAC levels. Furthermore, methomyl caused a significant (p < 0.001) reduction in sperm quality. Histopathological examination indicated testicular and renal damage with strong immunoreactivity for caspase-3. Functional and tissue damage was prevented in rats treated with a combination of methomyl and folic acid. This is ascribed to the ability of folate to directly scavenge reactive oxygen species and indirectly enhance cellular redox homeostasis. This study identified that folic acid supplementation may have a beneficial effect in preventing or reducing the deleterious effects of methomyl exposure on kidney as well as testis structure and function. Future studies should focus on the fertility outcome/pregnancy index in rats.

Effects of chronic exposure to mercury and cadmium alone and in combination on the coagulation system of Sprague-Dawley rats.

Water contamination with heavy metals may adversely affect our health. High metal levels lead to changes in blood coagulation processes, increasing the risk for cardiovascular disease. Exposure is not limited to a single metal but usually involves a mixture of metals. In this study 24 male Sprague-Dawley rats were exposed to cadmium (Cd) and mercury (Hg), alone and in combination, for 28 days at dosages equivalent to 1000 times the World Health Organization water limits. Scanning electron microscopy analysis revealed that both metals caused platelet activation. Cd significantly increased fibrin fibers thickness and caused aggregation and formation of dense matted deposits (DMDs). Hg reduced fibrin network formation. In the combination group, Hg appeared to augment the effect of Cd, and the presence of extensive DMDs or aggregates between the fibers, with no changes to the actual fibrin thickness, was observed.

Premature collagen fibril formation, fibroblast-mast cell interactions and mast cell-mediated phagocytosis of collagen in keloids.

Keloids are benign hyper-proliferative growths of fibrous tissue where increased fibroblast activity results in abnormal collagen deposition. Excessive inflammation is a characteristic feature of keloids, but little is known about the underlying ultrastructural features of keloids related to collagen processing, fibril and fiber formation, the interaction between fibroblasts and associated collagen fibers and mast cells. In this study, the ultrastructure of the dermis of keloid patients was evaluated using light and transmission electron microscopy techniques. Abnormal intracellular premature collagen fibril formation was observed. Phagocytosis of collagen fibrils by mast cells was a common ultrastructural feature of keloid tissue as was a close or direct association between fibroblasts and mast cells. Based on these findings and recent advances in knowledge related to collagen synthesis, fibril formation and processing, we hypothesize that keloid formation is primarily due to abnormal collagen synthesis where the consequent accumulation of collagen fibers causes increased mast cell recruitment and collagen phagocytosis. Subsequent release of mast cell-derived mediators then promotes further collagen synthesis. The observation of early formation in keloid tissue of premature insoluble collagen fibrils supports previous studies that enzymes such as procollagen C-proteinase are important early therapeutic targets.