ABSTRACT
The present study was designed to investigate the toxic effects (evaluated as histopathological changes) of sodium fluoride on the kidney in two consecutive generations of NMRI mice. An attempt to correlate the toxicity with the urinary elimination of fluoride has been made, as urinary fluoride excretion has been widely used as an indicator of fluoride intake and exposure. Six mixed (males and females) animal groups have been constituted by dividing the populations of mice derived from pregnant females (named "mothers" 0.5 mg sodium fluoride) treated with 0.5 mg sodium fluoride by daily gavage and pregnant females (named "mothers" 0.25 mg sodium fluoride) treated with 0.25 mg sodium fluoride by daily gavage; three types of sodium fluoride treatments were administrated: homeopathic, allopathic-homeopathic and allopathic. When the animals reached the adulthood, by randomization, they were selected in pairs for giving birth to the second generation of mice. No treatments were administrated to the second generation of mice; thus, the urinary elimination of fluoride in the second generation is attributed to exposure at sodium fluoride before birth. The administration of sodium fluoride to the first generation (F1) is realized until the mice reached the adulthood. For the first generation, the urine was collected at three times, every three weeks: at the age of four weeks, seven weeks and 11 weeks; single sampling urine, at the age of four weeks, has been conducted for the second generation. The urine samples have been analyzed using the ion selective electrode method for fluoride. For the histopathological examination, the animals were killed by cervical dislocation; the kidneys were collected in a 10% formalin solution. The preparation of samples for optical microscopy was realized with Hematoxylin-Eosin staining. The results indicate that the elimination of fluoride was similar (at the second evaluation, at 7-week-old of the first generation) for the both generations of mice. Histopathological observation of the kidney has revealed granular dystrophy of the renal tubules, necrosis of the endothelial cells and of the mesangial cells of renal glomerulus. The study indicates that different sodium fluoride treatments produce some pathological aspects of the kidneys and influence the urinary elimination of fluoride in two consecutive generations of mice. For the higher doses, the pathological changes of the kidney are more important, and the urinary elimination of fluoride is higher, especially for the allopathic doses.
Subject(s)
Cariostatic Agents/toxicity , Fluorides/urine , Kidney/drug effects , Sodium Fluoride/toxicity , Animals , Animals, Newborn , Female , Humans , Kidney/cytology , Kidney/pathology , Male , Mice , Pregnancy , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/urine , Toxicity TestsSubject(s)
Chlormadinone Acetate/toxicity , Kidney/drug effects , Lynestrenol/toxicity , Animals , Female , Guinea Pigs , Kidney/pathology , RabbitsABSTRACT
Because the kidney is the major excretory organ for drugs and toxins, it is especially susceptible to damage from such agents. While alternative medical therapies appear to be on an increase worldwide, there have been few case reports regarding their nephrotoxicity. However we have recently observed three patients who developed irreversible renal impairment, which we believe was due to such therapies.
Subject(s)
Acute Kidney Injury/etiology , Complementary Therapies , Homeopathy , Adult , Chelation Therapy/adverse effects , Female , Humans , Kidney/pathology , Middle AgedABSTRACT
ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , NF-E2-Related Factor 2 , Syzygium , Animals , NF-E2-Related Factor 2/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Syzygium/chemistry , Humans , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Male , Rats , Mitochondria/drug effects , Mitochondria/metabolism , NF-kappa B/metabolism , Plant Extracts/pharmacology , Signal Transduction/drug effects , HEK293 Cells , Oxidative Stress/drug effects , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Glycation End Products, Advanced/metabolism , Streptozocin , Rats, Wistar , Antioxidants/pharmacology , Rats, Sprague-DawleyABSTRACT
La tuberculosis urogenital constituye una manifestación local de una infección generalizada. El riñón es el primer órgano urinario afectado generalmente por diseminación errática de un foco pulmonar inicial. Si la tuberculosis urogenital no es diagnosticada y tratada a tiempo se producen lesiones evolutivas crónicas, que se describen en este artículo de revisión donde se destacan sus aspectos microbiológicos, anatomoclínicos e imagenológicos
Subject(s)
Humans , Male , Kidney/anatomy & histology , Kidney/pathology , Tuberculosis, Urogenital/classification , Tuberculosis, Urogenital/pathology , Homeopathic Clinical-Dynamic PrognosisABSTRACT
Foram estudados prospectivamente 33 pacientes cujos cistos tinham volume médio de 298,4 + 346,9 (30 1700) ml. A punção foi realizada sob anestesia local com agulha 18 gauge, de 20 cm. Após seu esvaziamento, injetou-se etanol absoluto no volume equivalente a um terço do volume aspirado, até o máximo de 100 ml. Os volume médios observados após um, três e seis meses foram 47,9 + 59,4 (0 286) ml, 25,2 + 42,8 (0 208) ml e 12,7 + 30 (0 120) ml, respectivamente. Após esse período, 30 (91por cento) apresentaram remissão total dos sintomas, 2 (6 por cento) mantiveram os sintomas, sendo um com cisto residual e outro sem cisto e um (3 por cento) apresentou melhora parcial dos sintomas / A prospective series of 33 patients with symptomatic simple renal cysts varying from 30 to 1700 ml, were considered eligible for the study. The cysts were punctured under local anesthesia with an 18 gauge, 20 centimeters needle. A volume of ethanol equivalent to one third of the aspirated volume, up to a maximum of 100 ml, was injected into the cyst and left there. After one, three and six months, the average volume of the cyst was 47.9 + 59.4 (0 - 286)ml, 25.2 + 42.8 (0 - 208)ml and 12.7 + 30 (0 - 120)ml, respectively. After this period, 30 patients (91per cent) showed total remission of the symptoms, two patients (6per cent) maintained them and one patient (3per c ent) had partial remission of the symptoms...