Multicentric reticulohistiocytosis post-COVID-19: a case report.

Background: Multicentric reticulohistiocytosis (MRH) stands as a rare and challenging systemic granulomatous disease characterized by its predilection for skin and joint involvement, confounding clinicians with its infrequent presentation and systemic manifestations. Case Description: This compelling case presentation unravels the intricate complexity of MRH, exemplifying its unique clinical course. Following mild upper respiratory coronavirus disease 2019 (COVID-19) symptoms, the patient manifested purplish-pink papular lesions on both the skin and mucosa, accompanied by debilitating arthralgias. A diagnostic skin biopsy, a pivotal tool in MRH diagnosis, confirmed the presence of this granulomatous disorder, underlining its systemic impact. Strategic therapeutic intervention involving a combination of steroids and methotrexate demonstrated remarkable efficacy, culminating in the resolution of symptoms within 3-month. The absence of malignancy upon thorough screening further amplifies the perplexing nature of MRH. Conclusions: This seminal case not only bridges the realms of rare systemic disorders but also marks the first known instance of MRH emerging post-COVID-19. It underscores the imperative consideration of MRH in analogous scenarios and provides invaluable insights into the nuanced interplay of MRH symptoms, diagnosis, and therapeutic strategies following viral triggers. This comprehensive exploration enriches our scientific understanding, offering nuanced perspectives on the manifestations and intricate dynamics of MRH in the context of post-viral sequelae.

Real-world experience utilizing the nuvision 4D intracardiac echocardiography catheter for left atrial appendage closure.

Transesophageal echocardiography (TEE) has been the preferred imaging modality to help guide left atrial appendage closure. Newer technologies such as the Nuvision 4D Intracardiac echocardiography (ICE) catheter allow for real-time 3D imaging of cardiac anatomy. There are no direct comparison studies for procedural imaging between TEE and 4D ICE. To evaluate the performance and safety of left atrial appendage (LAA) closure procedures with the Watchman FLX and Amulet, guided by the Nuvision 4D ICE Catheter. This retrospective observational analysis was conducted on institutional LAAO National Cardiovascular Data Registry from January 2022 to March 2023. Patients had undergone LAA closure procedures with the Watchman FLX or Amulet device guided by TEE or a 4D ICE Catheter. The primary outcome evaluated was successful LAAO device placement. A total of 121 patients underwent LAAO device placement with 46 (38.0%) patients guided by 4D ICE during LAAO implantation. The 4D ICE group had a shorter procedural time compared with TEE guidance. Post procedural 45-day TEE post implant was also comparable for both groups with no patients in either group having incomplete closure of the left atrial appendage and peri-device leak > 5 mm. No device related complications (device related access, stroke, or pericardial effusion) occurred in either group at follow-up. There was no significant difference in device implant success or post procedural outcomes at 45 days in either the TEE or 4D ICE group. However, there was a noticeable improvement in procedural time with the 4D ICE catheter.

Glycated LDL generates reactive species that damage cell components, oxidize hemoglobin and alter surface morphology in human erythrocytes.

Low-density lipoprotein (LDL) transports cholesterol to various tissues via the blood. Glycation of LDL occurs during hyperglycemic condition which is characterised by persistently high blood glucose level. Circulating erythrocytes can come in direct contact with glycated LDL (G-LDL). The objective of this study was to investigate the effect of G-LDL on human erythrocytes, specifically on hemoglobin, intracellular generation of reactive species and the antioxidant defence system. Isolated erythrocytes were incubated with G-LDL (3 and 6 mg/ml) and native LDL (6 mg/ml) at 37 °C for 24 h. Native LDL and G-LDL untreated erythrocytes were similarly incubated at 37 °C and served as control. G-LDL treatment increased hemolysis compared to control and native LDL-treated erythrocytes. Incubation of erythrocytes with G-LDL led to an increase in protein oxidation and lipid peroxidation while greatly decreasing the total sulfhydryl content. It also significantly enhanced hemoglobin oxidation, heme degradation, and the release of free iron moiety. Treatment with G-LDL led to an appreciable increase in the production of reactive oxygen and nitrogen species. The antioxidant power and activities of major antioxidant enzymes were drastically reduced, while critical membrane-bound enzymes were inhibited. The surface morphology of G-LDL-treated erythrocytes was altered leading to the formation of echinocytes. Importantly, treatment of erythrocytes with native LDL did not significantly affect the above-mentioned parameters and values were similar to the corresponding controls. Thus, G-LDL is cytotoxic to human erythrocytes and causes oxidative damage to cell components. This can reduce the oxygen-transporting ability of blood and also result in red cell senescence and anemia.

Amiodarone-Associated Optic Neuropathy in a Patient With Associated Arrhythmia.

Amiodarone is a commonly used antiarrhythmic used to treat atrial fibrillation and ventricular tachycardias. While this agent can present with pulmonary, thyroid, and hepatic side effects, it can also, less commonly cause neurologic toxicity, particularly optic neuropathy. Optic neuropathy can manifest as acute vision loss. The management of amiodarone-associated optic neuropathy (AAON) includes early recognition of symptom manifestation so that the medication can be discontinued promptly. Here, we describe a case of a 64-year-old male who developed acute onset complete left-sided vision loss after initiation of amiodarone.

Water Lung: An Interesting Case of Non-cardiogenic Pulmonary Edema in a Heart Failure Patient.

Contrast-induced pulmonary edema is a rare but life-threatening condition often missed in heart failure patients. We present a case of a 65-year-old female with a past medical history of coronary artery disease, diastolic heart failure, and chronic kidney disease who presented with chest pain. She received low osmolar intravenous (IV) contrast for cardiac catheterization. Within 24 hours of receiving the contrast, the patient developed respiratory distress, which was found to be secondary to pulmonary edema. Pulmonary edema was considered to be related to cardiogenic at first; however, the patient's physical examination was normal, with no jugular venous distention (JVD). A transthoracic echocardiogram showed a central venous pressure of 3 mmHg. The patient's respiratory condition improved after receiving an IV diuretic. Chart review showed that the patient had a similar presentation in the past, which was also thought to be related to heart failure leading to recurrent exposure to contrast. Non-cardiogenic pulmonary edema should be considered in the differential diagnosis of pulmonary edema in heart failure patients receiving contrast.

Studies on the interaction of 2,4-dibromophenol with human hemoglobin using multi-spectroscopic, molecular docking and molecular dynamics techniques.

2,4-Dibromophenol (DBP) has several industrial applications, including as a wood preservative and flame retardant. This study investigated the interaction between DBP and human hemoglobin (Hb) using spectroscopic, molecular docking and molecular dynamic techniques. The UV-visible spectra showed ground-state complex formation between DBP and Hb. Fluorescence studies revealed that DBP binding caused significant quenching of Hb fluorescence by the static quenching mechanism. The binding of DBP to Hb is a spontaneous process that involves van der Waals forces and hydrogen bonds. There is one DBP binding site on each Hb molecule that is located at the α1ß2 interface of Hb. DBP binding did not alter the microenvironment of tyrosine and tryptophan residues in Hb. Circular dichroism studies revealed that DBP increased the α-helical content of Hb. The intrinsic esterase activity of Hb was inhibited by DBP in a concentration-dependent manner. Molecular docking showed that DBP binds to Hb via hydrogen bonds, hydrophobic, van der Waals and π-π interactions. Molecular dynamics simulation confirmed that the Hb-DBP complex is stable. Overall, the results of this study clearly show that DBP induces structural changes and interferes with the function of Hb. This can have important implications for human health.Communicated by Ramaswamy H. Sarma.

Nickel chloride generates cytotoxic ROS that cause oxidative damage in human erythrocytes.

BACKGROUND: Nickel is a heavy metal that is regarded as a possible hazard to living organisms due to its toxicity and carcinogenicity. Nickel chloride (NiCl2), an inorganic divalent Ni compound, has been shown to cause oxidative stress in cells by altering the redox equilibrium. We have investigated the effect of NiCl2 on isolated human erythrocytes under in vitro condition. METHODS: Isolated erythrocytes were treated with different concentrations of NiCl2 (25-500 µM) for 24 h at 37 ºC. Hemolysates were prepared and several biochemical parameters were analyzed in them. RESULTS: Treatment of erythrocytes with NiCl2 enhanced the intracellular generation of reactive oxygen species (ROS). A significant increase in hydrogen peroxide levels and oxidation of proteins and lipids was also seen. This was accompanied by a reduction in levels of nitric oxide, glutathione, free amino groups and total sulfhydryl groups. NiCl2 treatment impaired both enzymatic and non-enzymatic defense systems, resulting in lowered antioxidant capacity and diminished ability of cells to quench free radicals and reduce metal ions. NiCl2 exposure also had an inhibitory effect on the activity of enzymes involved in pathways of glucose metabolism (glycolytic and pentose phosphate shunt pathways). Increased level of methemoglobin, which is inactive in oxygen transport, was also seen. The rate of heme breakdown increased resulting in the release of free iron. Exposure to NiCl2 led to considerable cell lysis, indicating damage to the erythrocyte membrane. This was supported by the inhibition of membrane bound enzymes and increase in the osmotic fragility of NiCl2 treated cells. NiCl2 treatment caused severe morphological alterations with the conversion of normal discocytes to echinocytes. All changes were seen in a NiCl2 concentration-dependent manner. CONCLUSION: NiCl2 generates cytotoxic ROS in human erythrocytes which cause oxidative damage that can decrease the oxygen carrying capacity of blood and also lead to anemia.

Vanillin attenuates CdCl2-induced cytotoxicity in isolated human erythrocytes.

Cadmium is a toxic heavy metal with no physiological role in the human body. Cadmium has high mobility due to its widespread industrial use, with no safe and effective therapeutic management. Cadmium toxicity manifests by increasing oxidative stress in target cells. We have explored the potential role of vanillin, a plant phenolic aldehyde and antioxidant, in mitigating cadmium chloride (CdCl2) induced hemotoxicity using isolated human erythrocytes. CdCl2 was added to erythrocytes, in the absence and presence of vanillin. Incubation of erythrocytes with CdCl2 alone inhibited methemoglobin reductase and enhanced methemoglobin level. Heme degradation and release of free iron (Fe2+), along with protein and membrane lipid oxidation, were also increased. A CdCl2-induced enhancement in reactive oxygen and nitrogen species was also seen, lowering the overall antioxidant power of cells. However, pre-incubation of erythrocytes with vanillin resulted in significant decreased generation of reactive species and prevented heme degradation and heme oxidation. Vanillin augmented the erythrocyte antioxidant capacity and reinstated the activities of major antioxidant, plasma membrane-bound and glucose metabolism enzymes. Scanning electron microscopy showed that CdCl2 treatment led to the formation of echinocytes which was prevented by vanillin. In all cases, no harmful effects of vanillin alone were seen. Thus, vanillin alleviates the toxicity of cadmium and can be potentially employed as a chemoprotectant against the damaging effects of this heavy metal.

Pentachlorophenol-induced hemotoxicity diminishes antioxidant potential and oxidizes proteins, thiols, and lipids in rat blood: An in vivo study.

Pentachlorophenol (PCP) is an excessively used wood preservative and pesticide, which has resulted in human exposure raising concerns about its potential toxic effects. This study is designed to evaluate the hemotoxicity of PCP in adult rats. Wistar rats were orally administered PCP (25-150 mg/kg bw) for five days while untreated (control) rats received corn oil. Animals were sacrificed, blood was taken and fractionated into plasma and red blood cells (RBC). PCP administration increased methemoglobin formation but decreased methemoglobin reductase activity. Significantly increased hydrogen peroxide level indicates initiation of oxidative stress condition in blood. PCP increased the oxidation of thiols, proteins and lipids, lowered glutathione levels, and compromised the antioxidant status of RBC in treated rats. Enzymes of the pathways of glucose breakdown, glycolysis and phosphogluconate pathway, were inhibited. Markers of liver damage were increased in the plasma of PCP-treated rats suggesting hepatotoxicity. This was confirmed by histopathological analysis of stained liver sections. Activity of xanthine oxidase, a reactive oxygen species (ROS) generating pro-oxidant enzyme, was increased. These hematological changes could be a result of the increased generation of ROS or direct chemical transformation by transient reaction species. These results show that PCP induces redox imbalance, diminishes antioxidant potential, inhibits metabolic pathways, and oxidizes cellular components in rat blood. This study suggests an elaborated possible molecular mechanism of PCP toxicity, and similar compounds so that methods can be devised to minimize its damaging effect.

Mancozeb-induced cytotoxicity in human erythrocytes: enhanced generation of reactive species, hemoglobin oxidation, diminished antioxidant power, membrane damage and morphological changes.

Mancozeb is an ethylene bis-dithiocarbamate fungicide extensively used in agriculture to safeguard crops from various fungal diseases. The general population is exposed to mancozeb through consumption of contaminated food or water. Here, we have investigated the effect of mancozeb on isolated human erythrocytes under in vitro conditions. Erythrocytes were treated with different concentrations of mancozeb (0, 5, 10, 25, 50, 100 µM) and incubated for 24 h at 37 °C. Analysis of biochemical parameters and cell morphology showed dose-dependent toxicity of mancozeb in human erythrocytes. Mancozeb treatment caused hemoglobin oxidation and heme degradation. Protein and lipid oxidation were enhanced, while a significant decrease was seen in reduced glutathione and total sulfhydryl content. A significant increase in the generation of reactive oxygen and nitrogen species was detected in mancozeb-treated erythrocytes. The antioxidant capacity and the activity of key antioxidant enzymes were greatly diminished, while crucial metabolic pathways were inhibited in erythrocytes. Damage to the erythrocyte membrane on mancozeb treatment was apparent from increased cell lysis and osmotic fragility, along with the impairment of the plasma membrane redox system. Mancozeb also caused morphological alterations and transformed the normal discoid-shaped erythrocytes into echinocytes and stomatocytes. Thus, mancozeb induces oxidative stress in human erythrocytes, impairs the antioxidant defense system, oxidizes cellular components, that will adversely affect erythrocyte structure and function.

Oral administration of curcumin and gallic acid alleviates pentachlorophenol-induced oxidative damage in rat intestine.

INTRODUCTION: Pentachlorophenol (PCP) is used as pesticide and wood preservative. We have previously shown that PCP causes oxidative damage in rat intestine. AIM: This study aimed to delineate the possible therapeutic potential of curcumin (CUR) and gallic acid (GA) against PCP-induced damage in rat intestine. METHODS: PCP alone group received 125 mg PCP/kg body weight/day orally for 4 days. Animals in combination groups received CUR or GA (100 mg/kg bw) for 18 days and PCP (125 mg/kg bw) for the last four days. Rats were sacrificed and intestinal preparations were analyzed for various parameters. RESULTS: Administration of PCP alone altered the activities of metabolic, antioxidant and brush border membrane enzymes. It also increased DNA-protein crosslinking and DNA-strand scission. Animals in combinations groups showed significant amelioration against PCP-induced oxidative damage. Histological abrasions were seen in PCP alone group which were reduced in the intestines of combination groups. CUR was more effective protectant than GA. CONCLUSIONS: CUR and GA protected rat intestine from PCP-mediated changes in the activities of metabolic, antioxidant and brush border membrane enzymes. They also prevented DNA damage and histological abrasions. The antioxidant character of CUR and GA may be responsible for the diminution of PCP-mediated oxidative damage.

Naproxen-Induced Evans Syndrome.

Evans syndrome is an autoimmune disorder characterized by the simultaneous occurrence of autoimmune hemolytic anemia and immune thrombocytopenic purpura. It can further be classified as primary Evans syndrome when it occurs by itself, or secondary Evans syndrome when it is associated with other autoimmune and lymphoproliferative disorders. Corticosteroids and immunoglobulins are the first-line treatments for primary Evans syndrome, and subsequent options include other immunosuppressive medications. Medical literature provides little information about the triggers of primary Evans syndrome. Knowing such information, however, is essential to recognize, treat and prevent the recurrence of the disease effectively.  We report a 68-year-old female who presented with shortness of breath, cough, bruises, scleral icterus, and dark urine after several days of naproxen therapy for pain. Further workup noted direct antiglobulin test positive for IgG, anemia, and thrombocytopenia. Imaging studies showed deep venous thrombosis. She was diagnosed with Evans syndrome and improved following prompt treatment with corticosteroids, anticoagulants, blood transfusion therapies, and discontinuation of naproxen. The prognosis of Evans syndrome is poor, variable, and characterized by relapses. Early diagnosis and treatment are therefore associated with better prognosis.  This case is critical because it shines a light on one of the major causes of Evans syndrome, reports a practical approach to treating the condition, and paves the way for future research on Evans syndrome. This case is also the first reported naproxen-induced Evans syndrome in the world's literature.

Esculin protects human blood cells from bioallethrin-induced toxicity: An ex vivo study.

Bioallethrin, a household insecticide, is a member of the pyrethroid family and is known for its adverse effects on human health. Human exposure to pyrethroids is unavoidable due to their widespread use in controlling several fatal vector-borne diseases, mostly in developing nations. Bioallethrin is known to induce oxidative stress in target cells, including erythrocytes. Here we have studied the protective effect of dietary antioxidant esculin on bioallethrin-induced damage in isolated human erythrocytes. The cells were incubated with 200 µM bioallethrin, without or with different concentrations of esculin (200, 400 and 600 µM), and the results compared to the untreated control samples. Bioallethrin-treated erythrocytes showed a significant increase in oxidative stress markers, like protein and lipid oxidation, accompanied by decrease in free amino groups and ratio of reduced to oxidized glutathione. There was enhanced generation of reactive oxygen and nitrogen species with changes in plasma membrane integrity. Bioallethrin oxidized hemoglobin to methemoglobin, which cannot transport oxygen. It altered the activities of antioxidant enzymes and lowered the electron donating and free radical quenching ability of erythrocytes. The cell morphology and redox system of erythrocyte membrane were also altered by bioallethrin. Treatment with esculin, prior to incubation with bioallethrin, led to significant restoration in all these parameters in an esculin concentration-dependent manner. Thus esculin attenuated the biolletherin-induced oxidative damage to erythrocytes. Esculin can, therefore, be an effective chemoprotectant against xenobiotic-induced toxicity in human erythrocytes.

Curcumin from Curcuma longa Linn. (Family: Zingiberaceae) attenuates hypochlorous acid-induced cytotoxicity and oxidative damage to human red blood cells.

Hypochlorous acid (HOCl) is a major oxidant produced by activated neutrophils via the myeloperoxidase catalyzed reaction. The production of HOCl eliminates a wide range of pathogens. However, HOCl can also cause significant oxidative damage in cells and tissues where it is generated. The protective effect of curcumin was studied on HOCl-induced oxidative damage to human red blood cells (RBC). Isolated RBC were incubated with HOCl at 37 °C in absence or presence of different concentrations of curcumin. Hemolysates were prepared and assayed for various biochemical parameters. Treatment of RBC with HOCl alone increased hemolysis, protein carbonyls, heme degradation and chloramines as compared to untreated control cells. This was accompanied by reduction in glutathione level, total sulfhydryls and free amino groups. HOCl also lowered the activities of major antioxidant enzymes and diminished the antioxidant power of RBC. Pre-treatment of RBC with different concentrations of curcumin resulted in concentration-dependent attenuation in all these parameters while curcumin alone had no significant effect. Scanning electron microscopy showed that curcumin prevented HOCl-induced morphological changes in RBC and restored their normal biconcave shape. Thus curcumin can be used as a chemoprotective agent to mitigate HOCl-induced oxidative damage to cells. These results also explain the beneficial effects of curcumin against Helicobacter pylori induced stomach ulcers, caused by excessive production of HOCl at the site of bacterial infection.

Pentachlorophenol causes redox imbalance, inhibition of brush border membrane and metabolic enzymes, DNA damage and histological alterations in rat kidney.

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage.

Protective effect of rutin against thiram-induced cytotoxicity and oxidative damage in human erythrocytes.

Thiram is a fungicide that is used to prevent fungal diseases in seeds and crops and also as an animal repellent. The pro-oxidant activity of thiram is well established. Rutin is a flavonoid glycoside present in many fruits and plants and has several beneficial properties, including antioxidant effects. We have previously shown that thiram causes oxidative damage in human erythrocytes. The present study was designed to evaluate the protective effect of rutin against thiram-induced damage in human erythrocytes. Treatment of erythrocytes with 0.5 mM thiram for 4 h increased the level of oxidative stress markers, decreased antioxidant power and lowered the activity of antioxidant and membrane bound enzymes. It also enhanced the generation of reactive oxygen and nitrogen species (ROS and RNS) and altered the morphology of erythrocytes. However, prior treatment of erythrocytes with rutin (0.5, 1 and 2 mM) for 2 h, followed by 4 h incubation with 0.5 mM thiram, led to a decrease in the level of oxidative stress markers in a rutin concentration-dependent manner. A significant restoration in the antioxidant power and activity of antioxidant enzymes was observed upon the treatment of erythrocytes with 1 and 2 mM rutin. Pre-incubation with rutin lowered the generation of ROS and RNS which will reduce oxidative damage in erythrocytes. The thiram-induced changes in cell morphology and activity of membrane-bound enzymes were also attenuated by rutin. These results suggest that rutin can be used to mitigate thiram-induced oxidative damage in human erythrocytes.

Hyperglycemia enhances the generation of ROS and RNS that impair antioxidant power and cause oxidative damage in human erythrocytes.

Hyperglycemia is a state in which excess glucose circulates in blood. Erythrocytes are in direct contact with this high glucose concentration and are greatly affected by it. We have examined the effect of hyperglycemic condition on isolated human erythrocytes under in vitro conditions. Erythrocytes were incubated with different concentrations of glucose (5, 15, 30, 45 mmol/L) for 24 h, and several biochemical parameters were determined. Treatment with high glucose concentrations increased heme degradation and methemoglobin level, while methemoglobin reductase activity was decreased. A significant increase in protein oxidation and lipid hydroperoxides with a decrease in total sulfhydryl content was seen. This suggested the generation of oxidative stress, which was confirmed by an enhanced production of reactive oxygen and nitrogen species. Hyperglycemia led to a significant decline in the antioxidant power of erythrocytes, lowering their ability to quench free radicals and reduce metal ions to lower oxidation states. The plasma membrane redox system was upregulated, while ascorbate free radical reductase activity was lowered. Glucose exposure inhibited the enzymes of glycolysis and hexose monophosphate shunt. Electron microscopy showed morphological changes resulting in the formation of echinocytes. Thus, the hyperglycemic condition generates reactive species that oxidize proteins, hemoglobin, and lipids; impair the total antioxidant capacity; and alter morphology in human erythrocytes.

Interaction of the insecticide bioallethrin with human hemoglobin: biophysical, in silico and enzymatic studies.

Bioallethrin is an insecticide that is widely used in households resulting in human exposure. Bioallethrin is cytotoxic to human erythrocytes. Here we have studied the interaction of bioallethrin with human hemoglobin (Hb) using in silico and biophysical approaches. Incubation of Hb (5 µM) with bioallethrin (1-50 µM) led to increase in absorbance at 280 nm while the Soret band at 406 nm was slightly reduced. The intrinsic fluorescence of Hb was enhanced with the appearance of a new peak around 305 nm. Synchronous fluorescence showed that the binding of bioallethrin to Hb mainly affects the tyrosine microenvironment. The structural changes in Hb were confirmed with a significant shift in CD spectra and about 25% loss of α-helix. Molecular docking and visualisation through Discovery studio confirmed the formation of Hb-bioallethrin complex with a binding energy of -7.3 kcal/mol. Molecular simulation showed the stability and energy dynamics of the binding reaction between bioallethrin and Hb. The structural changes induced by bioallethrin led to inhibition of the esterase activity of Hb. In conclusion, this study shows that bioallethrin forms a stable complex with human Hb which may lead to loss of Hb function in the body.Communicated by Ramaswamy H. Sarma.

Fructosylation of human insulin causes AGEs formation, structural perturbations and morphological changes: an in silico and multispectroscopic study.

Fructosylation of proteins results in the formation of advanced glycation end-products (AGEs). A diet rich in fructose along with hyperglycemia can cause fructose mediated glycation (fructosylation) of proteins, which results in AGEs formation. Insulin is a peptide hormone that is glycated when exposed to carbohydrates such as glucose. In this study, we have analysed the interaction of insulin with fructose and biophysically characterized fructose modified insulin. In silico studies performed through molecular docking and molecular dynamics simulation revealed that fructose binds to insulin with strong affinity resulting in the formation of insulin-fructose complex. Fructosylation of insulin caused hyperchromicity, loss of intrinsic fluorescence, gain in AGEs specific fluorescence and elevated the carbonyl and fructosamine content. Enhanced thioflavin T fluorescence suggested the presence of fibrillar structures at higher concentrations of fructose. Electron microscopy revealed the formation of characteristic amorphous and amyloid like aggregates at lower and higher concentrations of fructose, respectively. These findings show that fructosylation of insulin causes AGEs production, aggregation and alters its gross structural integrity. These changes may reduce the biological activity of insulin that can aggravate conditions like type II diabetes mellitus.Communicated by Ramaswamy H. Sarma.

Oral Administration of Copper Chloride Damages DNA, Lowers Antioxidant Defense, Alters Metabolic Status, and Inhibits Membrane Bound Enzymes in Rat Kidney.

Copper (Cu) is a heavy metal that is widely used in industries and is also an essential micronutrient for living beings. However, excess Cu is toxic and human exposure to high levels of this metal results in numerous adverse health effects. We have investigated the effect of oral administration of copper chloride (CuCl2), a Cu(II) compound, on various parameters of oxidative stress, cellular metabolism, and DNA integrity in the rat kidney. This was done to delineate the molecular mechanism of Cu(II) toxicity. Adult male rats were randomly divided into five groups. Animals in four CuCl2-treated groups were separately administered single acute oral dose of CuCl2 at 5, 15, 30, and 40 mg/kg body weight. Animals in the fifth group were not given CuCl2 and served as the control. All rats were sacrificed 24 h after the dose of CuCl2 and their kidneys removed. CuCl2 administration led to significant alterations in enzymatic and non-enzymatic parameters of oxidative stress. It changed the activities of metabolic and membrane bound enzymes and also decreased the activities of brush border membrane enzymes. CuCl2 treatment dose-dependently enhanced DNA damage and DNA-protein crosslinking in renal cells, when compared to the control group. The administration of CuCl2 also resulted in marked morphological changes in the kidney, with more prominent alterations at higher doses of CuCl2. These results clearly show that CuCl2 impairs the antioxidant defense system resulting in oxidative damage to the kidney.