fluoride-associated mitochondriopathy in human renal cells: an ultrastructural analysis

Reactive oxygen species (ros) and lipid peroxidation (lpo) have been considered to play an important role in the pathogenesis of chronic fluoride ion (f) toxicity. many studies have shown that f-induced apoptosis may be associated with oxidative stress and provoke the initiation of the apoptotic process. apoptosis is mainly regulated by complex pro- and anti-apoptotic gene families. the bcl-2 family of regulator proteins has been demonstrated to be involved in the regulation of apoptosis with bcl-2 inhibiting apoptosis and bax promoting it. both genes are widely present in the mitochondria and endoplasmic reticulum of the cells. the aim of this study was to evaluate f-associated mitochondriopathy in human renal cells. the patient sample comprised 64 children, aged 4-12 yr, with nephrotic syndrome due to minimal change disease (ns-mcd) who were divided into two groups: (i) group 1 (n=32) with a normal urinary f (≤1 mg/l) and (ii) group 2 (n=32) with a high urinary f (>1 mg/l). renal biopsies, taken for clinical diagnostic indications, were processed for ultrastructural analysis of the tubular parts by transmission electron microscopy (tem). the group 2 patients showed a remarkably high level of mitochondriopathy including mitochondrial edema, cristolysis, and electron dense deposits in the mitochondrial matrix. these findings may help in understanding f-associated nephrotoxicity in humans and in paving the way for the early diagnosis of f-induced renal impairment.