Expressions of LC3A,Beclin-1,Bcl-2 and Bax in liver of fluorosis rat

Objective To explore expressions of microtubule associated protein light chain 3A (LC3A),a mammalian homolog of yeast Atg6/vps30 (Beclin-1),B-cell leukemia/lymphoma 2 (Bcl-2),and Bcl-2 assaciated X protein (Bax) in livers of rats with fluorosis.Methods Thirty-six healthy Sprague-Dawley (SD) rats were randomly divided into three groups:a control group (supplied with drinking water containing sodium fluorideNaF of <1 mg/L),low fluorine group (5 mg/L NaF in drinking water),and high fluorine group (50 mg/L NaF in drinking water).The incidence of detal fluorosis in all the groups was determined after the 6-month treatment.The fluorine content in the urine and bone of the rats was measured with fluorine-ion method.The rats' liver function was tested with automatic blood chemical analyzer.The pathomorphologic changes in the livers of the rats were observed with light microscope.The protein expressions of LC3A,Beclin-1,Bcl-2,and Bax were detected with immunohistochemistry (IHC) method.Results Significantly increased urinary and bone fluoride contents were observed in the rats of low fluorine group (2.18±0.14 mg/L,237.42±18.48 mg/kg) and high fluorine group (2.40±0.19 mg/L,248.00±14.72 mg/kg) compared to those in the rats of control group (1.92±0.12 mg/L,185.57±13.27 mg/kg) (P<0.05 for all).In the rats of low and high fluorine groups,the hepatocytes were disorganized and swollen with cytoplasmic clearing.The activity of serum alanine transaminase (ALT) and aspartate aminotransferase (AST) significantly increased in the rats of low fluorine group (52.84±2.24 U/L,74.67±6.27U/L) and high fluorine group (135.52±13.52 U/L,154.46±12.66 U/L),both higher than those of the control rats (38.75±4.15 U/L,121.74±10.43 U/L)(P<0.05 for all).Significantly high expressed LC3A (35.35±2.71,44.10±6.72),Beclin-1 (57.56±12.1,74.76±18.67),and Bax (51.1±9.23,62.32±10.3),but low expressed Bcl-2 (55.18±8.36,39.05±6.91) were observed in the rats of low and high fluorine groups compared to those of the control rats (27.55±2.32,40.23±6.96,40.00±8.02,79.21±11.00) (P<0.05 for all).Conclusion Excessive fluorine can promote expressions of proteins related to autophagy and apoptosis of hepatocytes,which may play important roles in the pathogenesis of liver damage induced by chronic fluorosis.