FLUORIDE INDUCED NEPHROTOXICITY: APOPTOSIS, ULTRASTRUCTURAL CHANGES AND RENAL TUBULAR INJURY IN EXPERIMENTAL ANIMALS

Fluorosis is endemic in many countries across the globe. Most of the Indian states are endemic for fluorosis. Fluoride is known to cause many types of health complications and affects skeletal & soft tissues. The kidneys are one of the highly exposed organs for all the ingested toxins including fluoride. Therefore fluoride exposed subjects are highly vulnerable to fluoride induced nephrotoxicity. In recent years it has been demonstrated that the prevalence of renal impairment is remarkably high in different fluorosis endemic areas. Higher prevalence of CKD observed in central dry zone of Sri Lanka, a fluorosis endemic region. The prevalence of renal tubular dysfunctions is significantly high in residents of El Quel, which is also an endemic fluorosis area in Southern Algeria. On the basis of previous research reports it may be concluded that fluoride induces renal impairments and renal tubular injuries, cellular and sub-cellular ultrastructural changes. But all the research reports available are confined to animal models only. The data available on fluoride associated renal impairment in human is scant and limited to case reports and epidemiological studies. Due to the variation in types of animal models used in the studies, variations in quantity of fluoride administered and variations in route of fluoride administration, the generated insight cannot be translated to clinic. Therefore there is need to adopt a direct holistic approach to evaluate the adverse effects of fluoride on kidney structure and function in human subjects.

Potential Therapeutic Implications of Caffeic Acid in Cancer Signaling: Past, Present, and Future

Caffeic acid (CA) has been present in many herbs, vegetables, and fruits. CA is a bioactive compound and exhibits various health advantages that are linked with its anti-oxidant functions and implicated in the therapy and prevention of disease progression of inflammatory diseases and cancer. The anti-tumor action of CA is attributed to its prooxidant and anti-oxidant properties. CA’s mechanism of action involves preventing reactive oxygen species formation, diminishing the angiogenesis of cancer cells, enhancing the tumor cells’ DNA oxidation, and repressing MMP-2 and MMP-9. CA and its derivatives have been reported to exhibit anti-carcinogenic properties against many cancer types. CA has indicated low intestinal absorption, low oral bioavailability in rats, and pitiable permeability across Caco-2 cells. In the present review, we have illustrated CA’s therapeutic potential, pharmacokinetics, and characteristics. The pharmacological effects of CA, the emphasis on in vitro and in vivo studies, and the existing challenges and prospects of CA for cancer treatment and prevention are discussed in this review

Multiple Myeloma-Like Spinal MRI Findings in Skeletal Fluorosis: An Unusual Presentation of Fluoride Toxicity in Human

Endemic fluorosis is a worldwide environmental problem due to excessive fluoride, commonly due to increased drinking water fluoride levels but sometimes due to other sources such food with high fluoride content. In India, 21 of the 35 states are known to have health problems associated with fluoride toxicity. The present report is a case of a 50-year-old female who was seen with progressive spinal complications and a MRI of the spine suggestive of multiple myeloma. The MRI of the lumbo-sacral spine showed a diffuse and heterogeneous marrow signal of the lower dorsal and lumbo-sacral vertebrae. The MRI was also suggestive of coarse trabeculation and appeared predominantly hypointanse on the T1W image and had mixed signal intensity on the T2W image. These findings were suggestive of neoplastic bone marrow infiltration and the presence of a proliferative disorder, with multiple myeloma being the most likely. During the patient workup, it was found that other family members were also having similar complications and, after investigation of these family members, it was found that they are suffering from systemic fluorosis. The patient was then evaluated for skeletal fluorosis and this condition was found to be present. Multiple myeloma was ruled out by the finding of a negative serum protein electrophoresis. The spinal complications appeared to be mainly due to the compression of the spinal cord and nerve roots by protruding osteophytes, thickening of the posterior longitudinal ligament, and thickening of the ligamentum flavum resulting in a compressive myeloradiculopathy and compressive myelopathy. The finding of multiple myeloma- like findings on the spinal MRI in association with skeletal fluorosis was considered to be a very rare event. This case report underlines the need to consider the presence of spinal skeletal fluorosis when evaluating spinal complications with unusual pseudo-multiple myeloma-like changes on the spinal MRI