A study on dose and time-dependent effect of fluoride in rats

Abstract The purpose of this study was to see the effect of fluoride (F) in Wistar NIN rats in a dose and time-dependent manner. Male rats (n=36) were taken and were randomly divided into six groups (Group I: control, group II: 5 mg/L F, Group III: 10 mg/L F, Group IV: 15 mg/L F, Group V: 50 mg/L F and Group VI: 100 mg/L F). Animals were examined at 3-time points of 30, 60 and 90 days for F toxicity changes. The results indicated that the F induced dose and time-dependent diet intake, body weight gain, food efficiency ratio, dental fluorosis, urinary, serum, bone and teeth F levels and histopathological changes in liver and kidney tissue. The significant increase in exposure of F through water in groups V and VI as compared to other groups has shown alterations in their food efficiency ratio, body weight gain, and the significant increase in the urinary and serum F levels. Histopathology of the kidney showed few dilated tubules in the kidney of group VI compared to all other groups. Whereas histopathology of the liver showed microvacuolation in groups V and VI compared to groups I, II and III. However, there were no significant differences between the organ weight ratios of different organs among all the groups. In conclusion, the dose-dependent effect of F starts at 100, 50 and 15mg/L from first, second and third months respectively, however, there were no significant differences in 5 and 10 mg/L F groups after 3 months.</jats:p

Temperature-dependent structural and functional properties of a mutant (F71L) αA-crystallin: Molecular basis for early onset of age-related cataract

AbstractPreviously we identified a novel mutation (F71L) in the αA-crystallin gene associated with early onset of age-related cataract. However, it is not known how the missense substitution translates into reduced chaperone-like activity (CLA), and how the structural and functional changes lead to early onset of the disease. Herein, we show that under native conditions the F71L-mutant is not significantly different from wild-type with regard to secondary and tertiary structural organization, hydrophobicity and the apparent molecular mass of oligomer but has substantial differences in structural and functional properties following a heat treatment. Wild-type αA-crystallin demonstrated increased CLA, whereas the F71L-mutant substantially lost its CLA upon heat treatment. Further, unlike the wild-type αA-subunit, F71L-subunit did not protect the αB-subunit in hetero-oligomeric complex from heat-induced aggregation. Moreover, hetero-oligomer containing F71L and αB in 3:1 ratio had significantly lower CLA upon thermal treatment compared to its unheated control. These results indicate that α-crystallin complexes containing F71L-αA subunits are less stable and have reduced CLA. Therefore, F71L may lead to earlier onset of cataract due to interaction with several environmental factors (e.g., temperature in this case) along with the aging process.Structured summary of protein interactionsalphaA crystallin and alphaA crystallin bind by molecular sieving (View interaction)alphaA crystallin and alphaB crystallin bind by molecular sieving(View interaction