Toxic Effect Of Cypermethrin On Enzymes In Freshwater Fish Oreochromis Mossambicus (Tilapia)

In agriculture, excessive use of various pesticides had increased in developing countries. These pesticides may be highly toxic, not only to aquatic organisms like fishes but also to humans. In recent years, synthetic pyrethroids were developed for major uses in various agriculture practices and public health purposes. We aim to find the toxic Effect of Cypermethrin on Freshwater Fish Oreochromis mossambicus (Tilapia). The fish Oreochromis mossambicus were exposed for 30 days to various sub lethal concentrations (1/10, 1/20, and 1/30) of cypermethrin. After completion of a 30 days exposure, the fish Oreochromis mossambicus was sacrificed and tissue samples of muscle, liver, and kidney were analyzed. Decreased value of ALP, ACP, and Increased value of AST, ALT was observed in all the sub lethal exposure of cypermethrin on treated freshwater fish Oreochromis mossambicus at 30 days on comparing with the control group. High variation of AST and ALT were observed in the liver at 1/10th concentration of cypermethrin and elevated variation of ALP and ACP was observed in the liver at 1/10th concentration of sub lethal level for 30 days exposure. While comparing with the control group, the effects of cypermethrin on experimental fish showed increased levels of AST, ALT in the tissues of muscle, liver, and kidney of O. mossambicus, and the level of ACP and ALP were found in a decreased manner. Increased levels of ALT and AST activity observed in freshwater fishes may be due to the reduction of metabolic activity and concentration of ACP and ALP in various tissues due to cellular necrosis. In the present study, we found that the effect of cypermethrin alters the activity of various enzymes in freshwater fish Oreochromis mossambicus. It is concluded from this study that exposure to cypermethrin affects the enzyme activities of fish.

Cellular Injury and Death

Cell death occurs after an irreversible insult or stress overwhelms the cell’s compensatory mechanisms of homeostasis and repair. Cellular necrosis, apoptosis, and autophagy are increasingly understood to be interconnected biochemical processes that may coexist in vascular, inflammatory, and neurodegenerative conditions. Traditional classifications of cell death pathways are 1) necrosis; 2) programmed nuclear cell death, including apoptosis; and 3) autophagy. These processes occur in the context of variable cause and severity of injury, variable cellular metabolic and energy states, and variable fitness to compensate.

In vivo toxicities of the hospital effluent in Mahdia Tunisia

Hospital effluent (HE) is one of the most important sources of pharmaceutical released into the environment. This kind of pollution is a recognized problem for both human health and aquatic life. Consequently, in the present study, we assessed the effects of hospital untreated effluent on mice via biochemical and histopathological determinations. Female mice were given free access to water bottles containing untreated HE at different dilutions for 21 days. Then clinical biochemistry and histopathology evaluation were conducted. Serum biochemistry analysis showed the presence of significant increase in cholesterol, triglycerides, glycaemia and total bilirubin. However, phosphatase alkaline and urea activities have been significantly decreased compared to the control group. No significant variation was observed for the rest of the studied parameters (high-density lipoproteins; low-density lipoproteins and uric acid). Additionally, multiple alterations, including cellular necrosis, leucocyte infiltration and congestion, were observed in different tissues of mice exposed to the tested HE.

Photodynamic Therapy Using Hippo Pathway Inhibitor Verteporfin: A Potential Dual Mechanistic Approach in Treatment of Soft Tissue Sarcomas

Sarcoma is a widely varied and devastating oncological subtype, with overall five-year survival of 65% that drops to 16% with the presence of metastatic disease at diagnosis. Standard of care for localized sarcomas is predicated on local control with wide-local resection and radiation therapy, or, less commonly, chemotherapy, depending on tumor subtype. Verteporfin has the potential to be incorporated into this standard of care due to its unique molecular properties: inhibition of the upregulated Hippo pathway that frequently drives soft tissue sarcoma and photodynamic therapy-mediated necrosis due to oxidative damage. The initial anti-proliferative effect of verteporfin is mediated via binding and dissociation of YAP/TEAD proteins from the nucleus, ultimately leading to decreased cell proliferation as demonstrated in multiple in vitro studies. This effect has the potential to be compounded with use of photodynamic therapy to directly induce cellular necrosis with use of a clinical laser. Photodynamic therapy has been incorporated into multiple malignancies and has the potential to be incorporated into sarcoma treatment.

Rapid Hyperpolarization and Purification of the Metabolite Fumarate in Aqueous Solution

Hyperpolarized fumarate is a promising agent for carbon-13 magnetic resonance metabolic imaging of cellular necrosis. Molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting hyperpolarized fumarate solutions are contaminated with the catalyst, unreacted reagents, and reaction side product molecules, and are hence unsuitable for use <i>in vivo</i>. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved at a chosen concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow us to form hyperpolarized fumarate at a concentration of several hundred millimolar, at ¹³C polarization levels of 30-45%.

Rapid Hyperpolarization and Purification of the Metabolite Fumarate in Aqueous Solution

Hyperpolarized fumarate is a promising agent for carbon-13 magnetic resonance metabolic imaging of cellular necrosis. Molecular imaging applications require nuclear hyperpolarization to attain sufficient signal strength. Dissolution dynamic nuclear polarization is the current state-of-the-art methodology for hyperpolarizing fumarate, but this is expensive and relatively slow. Alternatively, this important biomolecule can be hyperpolarized in a cheap and convenient manner using parahydrogen-induced polarization. However, this process requires a chemical reaction, and the resulting hyperpolarized fumarate solutions are contaminated with the catalyst, unreacted reagents, and reaction side product molecules, and are hence unsuitable for use <i>in vivo</i>. In this work we show that the hyperpolarized fumarate can be purified from these contaminants by acid precipitation as a pure solid, and later redissolved at a chosen concentration in a clean aqueous solvent. Significant advances in the reaction conditions and reactor equipment allow us to form hyperpolarized fumarate at a concentration of several hundred millimolar, at ¹³C polarization levels of 30-45%.

Complex effects of pH on ROS from mitochondrial complex II driven complex I reverse electron transport challenge its role in tissue reperfusion injury

ABSTRACTGeneration of mitochondrial reactive oxygen species (ROS) is an important process in triggering cellular necrosis and tissue infarction during ischemia-reperfusion (IR) injury. Ischemia results in accumulation of the metabolite succinate. Rapid oxidation of this succinate by mitochondrial complex II (Cx-II) during reperfusion reduces the co-enzyme Q (Co-Q) pool, thereby driving electrons backward into complex-I (Cx-I), a process known as reverse electron transport (RET), which is thought to be a major source of ROS. During ischemia, enhanced glycolysis results in an acidic cellular pH at the onset of reperfusion. While the process of RET within Cx-I is known to be enhanced by a high mitochondrial trans-membrane ΔpH, the impact of pH itself on the integrated process of Cx-II to Cx-I RET has not been fully studied. Using isolated mitochondria under conditions which mimic the onset of reperfusion (i.e., high [ADP]). We show that mitochondrial respiration (state 2 and state 3) as well as isolated Cx-II activity are impaired at acidic pH, whereas the overall generation of ROS by Cx-II to Cx-I RET was insensitive to pH. Together these data indicate that the acceleration of Cx-I RET ROS by ΔpH appears to be cancelled out by the impact of pH on the source of electrons, i.e. Cx-II. Implications for the role of Cx-II to Cx-I RET derived ROS in IR injury are discussed.

Cardiomyopathies and Adrenal Diseases

Cardiomyopathies are myocardial disorders in which heart muscle is structurally and/or functionally abnormal. Previously, structural cardiomyocyte disorders due to adrenal diseases, such as hyperaldosteronism, hypercortisolism, and hypercatecholaminism, were misunderstood, and endomyocardial biopsy (EMB) was not performed because was considered dangerous and too invasive. Recent data confirm that, if performed in experienced centers, EMB is a safe technique and gives precious information about physiopathological processes implied in clinical abnormalities in patients with different systemic disturbances. In this review, we illustrate the most important features in patients affected by primary aldosteronism (PA), Cushing’s syndrome (CS), and pheochromocytoma (PHEO). Then, we critically describe microscopic and ultrastructural aspects that have emerged from the newest EMB studies. In PA, the autonomous hypersecretion of aldosterone induces the alteration of ion and water homeostasis, intracellular vacuolization, and swelling; interstitial oedema could be a peculiar feature of myocardial toxicity. In CS, cardiomyocyte hypertrophy and myofibrillolysis could be related to higher expression of atrogin-1. Finally, in PHEO, the hypercontraction of myofilaments with the formation of contraction bands and occasional cellular necrosis has been observed. We expect to clear the role of EMB in patients with cardiomyopathies and adrenal disease, and we believe EMB is a valid tool to implement new management and therapies.

Fricke Dosimetry as a Tool to Quality Control of Photodynamic Therapy

Photodynamic therapy (PDT) consists of the association of a photosensitizing agent with a light source in order to cause cellular necrosis. Methylene blue, toluidine blue and malachite green are photosensitizers derived from dyes that are widely accepted in medicine, as they have low toxicity and are low cost. PDT is an alternative treatment for cancer, with significant advantages over procedures such as surgery/chemotherapy. Our laboratory has studied the Fricke solution doped with photosensitizers in an approach to obtain a quality control for PDT. The Fricke solution was prepared with ammoniacal ferrous sulfate, sodium chloride and sulfuric acid in water. The solutions modified with photosensitizers were prepared by adding 0.1 g/100 mL of the dyes. A volume of 2.6 ml of the Fricke solution modified with photosensitizers were transferred to test tubes and irradiated. The irradiated solutions had their optical densities measured in a spectrophotometer. The samples were irradiated with LED (Light Emitting Diodes) in acrylic phantoms. The FATA samples irradiated with LED showed the sensitivity of the dosimeters to red, blue, green and yellow light. A calibration curve with correlation coefficient of 0.9884 for the red light was obtained; 0.9752 for blue light; 0.9644 for the green light and 0.9768 for the yellow light. The fact that a sensitivity of the dosimeters to the LED has been occurred indicates that the PDT could be realized with LED, with lower costs than with laser. This work suggested that FATA dosimeters can be used for quality control of PDT.

Tadalafil combined with remote ischemic preconditioning in the prevention of renal ischemia/reperfusion injury

PURPOSE: This study aimed to evaluate whether the combination of tadalafil treatment and remote ischemic preconditioning may provide protection against ischemia reperfusion injury (I/R) in kidneys of rats. METHODS: Twenty-four male Wistar rats weighing 280-300g were randomly divided into 3 groups: Group 1 - (control), only right nephrectomy was performed. No treatment with tadalafil. Group II - Left renal ischemia, right nephrectomy, without remote preconditioning, treatment with tadalafil (1.0 mg/kg, oral). Group III - Left renal ischemia, right nephrectomy, with remote preconditioning, treatment with tadalafil. RESULTS: 24 h after, urea and creatinine dosage and histopathology of the ischemic kidneys were performed. In the left kidney of control group rats, a higher degree of cellular necrosis was observed when compared to the tadalafil group, with and without remote preconditioning. On the preconditioning + tadalafil group rats, there was a significant reduction in histological parameters when compared to the Ischemia + tadalafil group rats (p<0.05). In group III, comparing to other groups, a significant improvement of the left kidney function was observed, through the lower values ​​of the urea and creatinine dosages. CONCLUSION: This study demonstrated protective effects of remote preconditioning + tadalafil in an experimental model of renal I/R in the rat. The results demonstrated that a single dose of tadalafil prior to renal I/R attenuated the histopathological lesions, especially cellular necrosis, and renal function tests.