Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes. Conversely, in FSGS, AMPK-activation using metformin (MF) mitigated podocytopenia and azotemia. Observational studies also support beneficial effects of MF on proteinuria and chronic kidney disease (CKD) outcomes in diabetes. A randomized controlled trial (RCT) to test MF in podocyte injury with FSGS has not yet been conducted. Methods: We report the rationale and design of phase 2, double-blind, placebo-controlled RCT evaluating the efficacy and safety of MF as adjunctive therapy in FSGS. By randomizing 30 patients with biopsy-confirmed FSGS to MF or placebo (along with standard immunosuppression), we will study mechanistic biomarkers that correlate with podocyte injury or depletion and evaluate outcomes after 6 months. We specifically integrate novel urine, blood, and tissue markers as surrogates for FSGS progression along with unbiased profiling strategies. Results and Conclusion: Our phase 2 trial will provide insight into the potential efficacy and safety of MF as adjunctive therapy in FSGS-a crucial step to developing a larger phase 3 study. The mechanistic assays here will guide the design of other FSGS trials and contribute to understanding AMPK activation as a potential therapeutic target in FSGS. By repurposing an inexpensive agent, our results will have implications for FSGS treatment in resource-poor settings.

Relationships between growth indicators, liver and kidney function markers, and blood concentrations of essential and potentially toxic elements in environmentally exposed young children.

Environmental exposure to multiple metals and metalloids is widespread, leading to a global concern relating to the adverse health effects of mixed-metals exposure, especially in young children living around industrial areas. This study aimed to quantify the concentrations of essential and potentially toxic elements in blood and to examine the potential associations between multiple elements exposures, growth determinants, and liver and kidney function biomarkers in children living in several industrial areas in Dhaka, Bangladesh. The blood distribution of 20 trace elements As, Ag, Bi, Br, Cd, Co, Cr, Cu, I, Mn, Hg, Mo, Ni, Pb, Se, Sb, Tl, V, U, and Zn, growth determinants such as body mass index and body fats, blood pressure, liver and kidney injury biomarkers including serum alanine aminotransferase and alkaline phosphatase activities, serum calcium, and creatinine levels, blood urea nitrogen, and hemoglobin concentrations, and glomerular filtration rate were measured in 141 children, aged six to 16 years. Among these elements, blood concentrations of Ag, U, V, Cr, Cd, Sb, and Bi were measured below LOQs and excluded from subsequent statistical analysis. This comprehensive study revealed that blood concentrations of these elements in children, living in industrial areas, exceeded critical reference values to varying extents; elevated exposure to As, Pb, Br, Cu, and Se was found in children living in multiple industrial areas. A significant positive association between elevated blood Tl concentration and obesity (ß = 0.300, p = 0.007) and an inverse relationship between lower As concentration and underweight (ß = -0.351, p < 0.001) compared to healthy weight children indicate that chronic exposure to Tl and As may influence the metabolic burden and physical growth in children. Concentration-dependent positive associations were observed between the blood concentrations of Cu, Se, and Br and hepatic- and renal dysfunction biomarkers, an inverse association with blood Mo and I level, however, indicates an increased risk of Cu, Se, and Br-induced liver and kidney toxicity. Further in-depth studies are warranted to elucidate the underlying mechanisms of the observed associations. Regular biomonitoring of elemental exposures is also indispensable to regulate pollution in consideration of the long-term health effects of mixed-elements exposure in children.

Screening for antimicrobial residues in poultry eggs in Bangladesh using Charm II radio-receptor assay technique following validation.

The aim of the study was to screen for the presence of antimicrobial residues in poultry eggs from Bangladesh using the Charm II radio-receptor assay in the absence of expensive confirmatory instrumentation. This was based on cut-off values as set in the validation guidelines according to Commission Decision 2002/657/EC and Commission Implementing Regulation (EU) 2021/808. Fortified eggs spiked with fixed concentrations of doxycycline, erythromycin A, sulphamethazine, and benzylpenicillin were used to determine the cut-off values and detection capabilities (CCß). Other validation parameters included were applicability, ruggedness, and robustness. A total of 201 egg mix samples from native organic chicken, duck, and commercial farm-raised laying hens (both brown and white eggs) were tested and after analysis 13%, 10%, and 4.5% of the egg mix samples showed positive signals for sulphonamides, macrolides/lincosamides, and tetracyclines, respectively. Presence of multiple drug residues were also suspected in 11 out of 201 egg mix samples.

Effects of shipwrecks on spatiotemporal dynamics of metal/loids in sediments and seafood safety in the Bay of Bengal.

Metal/loid pollution from shipwrecking activities has drawn significant concern due to their persistent threat to the marine ecosystem and human health. We investigated the spatiotemporal distribution, pollution characteristics, risks, sources, and potential impact of metal/loids in the sediments and seafood in the Bay of Bengal at nearby open beaching shipwrecking yards in Bangladesh. We collected 78 sediments and 208 seafood samples from the exposed and control sites from 2018 to 2020 during the dry and wet seasons. The concentrations of 16 elements, including cadmium, arsenic, lead, chromium, manganese, copper, zinc, iron, tin, antimony, nickel, cobalt, molybdenum, vanadium, selenium, and thallium were measured using validated inductively coupled plasma-mass spectrometry (ICP-MS) methods. Based on the pollution indices (enrichment factor, geoaccumulation index, pollution index, and pollution load index), lead, arsenic, cadmium, selenium, copper, zinc, and tin from the dry season showed higher contaminations compared to the wet and their concentrations were increased from 2018 to 2020 with seasonal fluctuations. Sediment cadmium and arsenic posed relatively higher and moderate ecological risks. Health risk analysis indicated that lead, cadmium, and inorganic arsenic (estimated) in seafood species pose a possible health threat to the general population. Further, there were possible ecological and health risks for the metal/loids in combination based on the ecological risk index in sediment and the hazard index in seafood, respectively. Source apportionment suggested that anthropogenic activities through uncontrolled shipwrecking operations over the last four decades were the largest polluting dominator, contributing 55-77% of the metal/loid concentrations. Therefore, the data may inform mitigation strategies for emission control at the shipwrecking yards to protect marine ecosystems and their local population.

LPS/TLR4 Pathways in Breast Cancer: Insights into Cell Signalling.

BACKGROUND: Cancer cells are usually recognized as foreign particles by the immune cells. Mounting evidence suggest an important link between toll-like receptors (TLRs) and carcinogenesis. This review article focused on the role of TLRs, especially TLR4, in breast cancer. METHODS: Research data on TLRs and cancer was explored in PubMed, Scopus, Google Scholar and reviewed. Although some pioneer works are referenced, papers published in the last ten years were mostly cited. RESULTS: TLRs are widely investigated pattern recognition receptors (PRR), and TLR4 is the most studied TLRs, implicated with the occurrence of several types of cancers, including breast cancer. TLR4 activation occurs via the binding of its ligand lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria. Upon LPS binding, TLR4 dimerizes and recruits downstream signalling and/or adapter molecules, leading to gene expression related to cancer cell proliferation, survival, invasion, and metastasis. Although LPS/TLR4 signalling seems a single signal transduction pathway, the TLR4 activation results in the activation of multiple diverse intracellular networks with huge cellular responses in both immune and cancer cells. The role of TLR4 in the growth, invasion, and metastasis of breast cancer is attracting huge attention in oncology research. Several clinical and preclinical studies utilize both TLR4 agonists and antagonists as a treatment option for cancer therapy, either as monotherapy or adjuvants for vaccine development. CONCLUSION: This review narrates the role of LPS/TLR4 signalling in breast cancer development and future prospects for targeting LPS/TLR4 axis in the treatment of breast cancer.

Effects of storage conditions on the stability and distribution of clinical trace elements in whole blood and plasma: Application of ICP-MS.

BACKGROUND: Knowledge of trace element stability during sample handling and preservation is a prerequisite to produce reliable test results in clinical trace element analysis. METHOD: An alkaline dissolution method has been developed using inductively coupled plasma mass spectrometry to quantify eighteen trace element concentrations: vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, bromine, molybdenum, cadmium, antimony, iodine, mercury, thallium, lead, and bismuth in human blood, using a small sample volume of 0.1 mL. The study evaluated the comparative effects of storage conditions on the stability of nutritionally essential and non-essential elements in human blood and plasma samples stored at three different temperatures (4 °C, -20 °C and -80 °C) over a one-year period, and analysed at multiple time points. The distribution of these elements between whole blood and plasma and their distribution relationships are illustrated using blood samples from 66 adult donors in Queensland. RESULTS: The refrigeration and freezing of blood and plasma specimens proved to be suitable storage conditions for many of the trace elements for periods up to six months, with essentially unchanged concentrations. Substantially consistent recoveries were obtained by preserving specimens at -20 °C for up to one year. Ultra-freezing of the specimens at -80 °C did not improve stability; but appeared to result in adsorption and/or precipitation of some elements, accompanied by a longer sample thawing time. A population sample study revealed significant differences between the blood and plasma concentrations of six essential elements and their relationships also varied significantly for different elements. CONCLUSION: Blood and plasma specimens can be reliably stored at 4 °C for six months or kept frozen at -20 °C up to one year to obtain high quality test results of trace elements.

Development and Validation of an ICP-MS Method and Its Application to Determine Multiple Trace Elements in Small Volumes of Whole Blood and Plasma.

Essential and nonessential element concentrations in human blood provide important information on the nutritional status of individuals and can assist in the screening or diagnosis of certain disorders and their association with other causative factors. A simple and sensitive method, suitable for use with small sample volumes, for quantification of multiple trace element concentrations in whole blood and plasma has been developed using inductively coupled plasma-mass spectrometry. Method validation was performed using standard reference materials of whole blood and serum using varying sample treatments with nitric acid, water and hydrogen peroxide. The method was applied to quantify the trace element concentrations in whole blood and plasma samples (0.1 mL) from 50 adult blood donors in Queensland. The whole blood sample (5 mL) was collected in Vacutainer tubes with K2EDTA as anticoagulant. The developed method was able to quantify, in blood and plasma samples over a wide range of concentrations, several essential elements: cobalt, copper, zinc, iron, manganese and selenium; the nutritionally probably essential elements vanadium and strontium; and nonessential elements including lead, cadmium, arsenic, caesium, barium, thallium and uranium. Significant differences (P < 0.0001) were observed between whole blood and plasma concentrations for 13 elements; 5 of the measured elements, cobalt (0.49 vs. 0.36 µg/L), copper (1.0 vs. 0.75 mg/L), strontium (28 vs. 16 µg/L), barium (1.5 vs. 0.64 µg/L) and thallium (0.06 vs. 0.03 µg/L), had higher mean concentrations in plasma than in blood. Whole blood concentrations of nine trace elements were significantly correlated (P < 0.0001) with plasma concentrations. The distribution of the trace elements between human blood and plasma varied considerably for the different elements. These results indicate that, using a small sample volume, this assay is suitable for the evaluation of nutritional status as well as in monitoring human toxic elemental exposures.

Nutritional Composition and Bioactive Compounds in Tomatoes and Their Impact on Human Health and Disease: A Review.

Tomatoes are consumed worldwide as fresh vegetables because of their high contents of essential nutrients and antioxidant-rich phytochemicals. Tomatoes contain minerals, vitamins, proteins, essential amino acids (leucine, threonine, valine, histidine, lysine, arginine), monounsaturated fatty acids (linoleic and linolenic acids), carotenoids (lycopene and ß-carotenoids) and phytosterols (ß-sitosterol, campesterol and stigmasterol). Lycopene is the main dietary carotenoid in tomato and tomato-based food products and lycopene consumption by humans has been reported to protect against cancer, cardiovascular diseases, cognitive function and osteoporosis. Among the phenolic compounds present in tomato, quercetin, kaempferol, naringenin, caffeic acid and lutein are the most common. Many of these compounds have antioxidant activities and are effective in protecting the human body against various oxidative stress-related diseases. Dietary tomatoes increase the body's level of antioxidants, trapping reactive oxygen species and reducing oxidative damage to important biomolecules such as membrane lipids, enzymatic proteins and DNA, thereby ameliorating oxidative stress. We reviewed the nutritional and phytochemical compositions of tomatoes. In addition, the impacts of the constituents on human health, particularly in ameliorating some degenerative diseases, are also discussed.

Ameliorative effects of ethanolic constituents of Bangladeshi propolis against tetracycline-induced hepatic and renal toxicity in rats.

The study reports the phenolic composition of propolis from Bangladesh and its ameliorative effects against tetracycline-induced hepatonephrotoxicity in rats. Male Wistar Albino rats (n = 18) were randomly divided into three following groups: (1) normal control, (2) tetracycline-treatment (200 mg kg-1  rat-1 ), and (3) tetracycline (200 mg kg-1  rat-1 ) + propolis (100 mg kg-1  rat-1 ) treatments. The ethanolic extract of propolis contained major phenolic acids as well as a flavonoid, rutin. Oral exposure to tetracycline caused severe hepatic and renal damage as indicated by significant alterations in liver marker enzymes in rat serum: bilirubin and protein concentrations, lipid profile, and markers of kidney function when compared with controls. The observed biochemical perturbations were accompanied by histopathological changes. Co-administration with propolis extract, however, prevented the changes in biochemical parameters, as revealed by maintenance of cell membrane integrity and regulation of lipid profile and the conservation of the histoarchitecture. PRACTICAL APPLICATIONS: Propolis is a resinous honeybee product which is becoming increasingly popular due to its potential contributions to human health. The phenolic compounds identified in propolis from Bangladesh were effective against tetracycline-induced hepatic and renal toxicity. Propolis may be a promising natural product in reducing the effects of chronic liver and kidney damage.

Antioxidant Potential, Subacute Toxicity, and Beneficiary Effects of Methanolic Extract of Pomelo (Citrus grandis L. Osbeck) in Long Evan Rats.

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandis L. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%), γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli's risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.

Protective Role of Syzygium Cymosum Leaf Extract Against Carbofuran-Induced Hematological and Hepatic Toxicities.

The aim of the present study was to evaluate the protective effect of Syzygium cymosum leaf methanol extract (SCL) against carbofuran (CF)-induced hepatotoxicity in Sprague-Dawley rats, along with the identification and quantification of polyphenolic composition by high-performance liquid chromatography (HPLC). Results revealed the presence of alkaloids, tannins, and flavonoids in SCL. Similarly, HPLC analysis suggests that SCL contains some known important antioxidants, such as rutin, benzoic acid, and salicylic acid that could be responsible for the hepatoprotective activity of the extract. In CF-exposed rats, significant hematological alterations along with histological changes were marked by the presence of necrosis, congestion, and inflammation. CF-intoxication also showed an increase in lipid peroxidation and decrease in cellular antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) levels in rats compared with the control group. Furthermore, coadministration of SCL significantly ameliorated the abnormalities and improved the cellular arrangement in experimental animals. SCL also reversed the alteration of hematological and biochemical parameters and brought them back to normal levels as compared to the control group. In conclusion, S. cymosum may be one of the best sources of natural antioxidant compounds that can be used in the treatment of oxidative stress and stress-related diseases and disorders.

Ganoderma lucidum and Auricularia polytricha Mushrooms Protect against Carbofuran-Induced Toxicity in Rats.

The current study aimed to investigate the ameliorative effects of two types of mushrooms, Ganoderma lucidum (GL) and Auricularia polytricha (AP), against carbofuran- (CF) induced toxicity in rats. Male Wistar rats (n = 42) were divided into six equal groups. The rats in the negative control group received oral administration of CF at 1 mg/kg with the normal diet for 28 days. The treatment groups received oral administration of ethanolic extract of GL or AP at 100 mg/kg followed by coadministration of CF at 1 mg/kg with the normal diet for the same experimental period, respectively. In the CF alone treated group, there were significant decreases in the erythrocytic and thrombocytic indices but increases in the concentrations of the total leukocytes, including the agranulocytes. A significant increase in all of the liver function biomarkers except albumin, in lipid profiles except high-density lipoprotein, and in the kidney function markers occurred in the negative control group compared to the rats of the normal control and positive control groups. The coadministration of mushroom extracts significantly ameliorated the toxic effects of the CF. The GL mushroom extract was more efficacious than that of the AP mushroom, possibly due to the presence of high levels of phenolic compounds and other antioxidants in the GL mushroom.

Antihyperglycemic, Antidiabetic, and Antioxidant Effects of Garcinia pedunculata in Rats.

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.

Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats.

Increases in the incidence of cardiovascular disease (CVD) have aroused strong interest in identifying antioxidants from natural sources for use in preventive medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an important herbal and medicinal plant reputed for its antioxidant, nutritious and therapeutic uses. The aim of the present study was to investigate the cardio-protective effects of ethanol extracts of C. macroptera peel and pulp against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for 45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days. Our findings indicated that subcutaneous injection of ISO induced severe myocardial injuries associated with oxidative stress, as confirmed by elevated lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and anti-peroxidative enzymes, including glutathione peroxidase, glutathione reductase and glutathione-S-transferase, compared with levels observed in control animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO administration however, significantly improved many of the investigated biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid profile and oxidative stress markers. The fruit peel extract showed stronger cardio-protective effects than the pulp extract. The biochemical findings were further confirmed by histopathological examinations. Overall, the increased endogenous antioxidant enzyme activity against heightened oxidative stress in the myocardium is strongly suggestive of the cardio-protective potential of C. macroptera.

Protective mechanism of turmeric (Curcuma longa) on carbofuran-induced hematological and hepatic toxicities in a rat model.

CONTEXT: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. OBJECTIVE: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. MATERIALS AND METHODS: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. RESULTS: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 µM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. DISCUSSION AND CONCLUSION: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.

Assessment of Toxicity and Beneficiary Effects of Garcinia pedunculata on the Hematological, Biochemical, and Histological Homeostasis in Rats.

This study was undertaken to investigate the toxicological profile of a methanolic extract of Garcinia pedunculata fruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castelli's risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates that G. pedunculata fruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.

Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats.

Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n = 32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats.

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.

Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats.

Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats.

This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.