Role of p53-mediated mitochondrial apoptotic pathway in arsenic liver injury caused by coal-burning / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the apoptosis of hepatocytes in arsenic poisoning rats caused by coal-burning and explore the effects of p53-induced mitochondrial apoptotic pathway on arsenic liver injury.METHODS Wistar rats were fed with 164.74 pp m arsenic conta minated grain at the levels of 15%,30% and 60% (arsenic contents were 25,50 and 100 mg·kg -1 ,respectively)for 90 d. The arsenic contents of urine and hair,apoptosis of hepatocytes and mRNA expression of p53,Bax and Bcl2 in peripheral blood and hepatocytes were evaluated.At the sa me ti me,protein expression of p53, Bax and Bcl2 in hepatocytes were analyzed.RESULTS The arsenic contents of urine and hair increased with the elevation of arsenic dose.The apoptotic rate of hepatocytes in arsenic 50 and 100 mg·kg -1 group were 16.49 ±2.06 and 15.83 ±1 .28,respectively which were significantly higher than the control group and arsenic 25 mg·kg -1 group (9.00 ±0.59 and 9.27 ±0.36,respectively,P <0.05).p53 mRNA expression of peripheral blood in arsenic 100 mg·kg -1 group was 2.69 ±1 .84 while p53 mRNA expression of hepatocytes in arsenic 25,50 and 100 mg·kg -1 group were 1 .63 ±0.28, 1 .91 ±0.38 and 1 .71 ±0.18,respectively which were significantly higher than the control group (0.86 ± 0.15 and 1 .22 ±0.12,respectively,P<0.05).Bax mRNA expression of peripheral blood in arsenic 50 and 100 mg·kg -1 group were 1 .36 ±0.30 and 1 .94 ±0.65 while Bax mRNA expression of hepatocytes in arsenic 100 mg·kg -1 group was 1 .34 ±0.23 which were significantly higher than the control group (0.77 ±0.15 and 0.84 ±0.34,respectively,P<0.05).Bcl2 mRNA expression of hepatocytes in arse-nic 100 mg·kg -1 group was 0.98 ±0.50 which was significantly lower than the control group (2.14 ± 1 .15,P<0.05).p53 protein expression of hepatocytes in arsenic 25,50 and 100 mg·kg -1 group were 1 .06 ±0.56,1 .15 ±0.77 and 0.74 ±0.27,respectively while Bax protein expression of hepatocytes in arsenic 50 and 100 mg·kg -1 group were 0.74 ±0.43 and 0.69 ±0.37 which were significantly higher than the control group (0.36 ±0.1 9 and 0.25 ±0.09,respectively,P<0.05).CONCLUSION Arsenic can induce hepatocytes apoptosis and p53-mediated mitochondrial apoptotic pathway may be involved in the develop ment of rat liver injury in arsenic poisoning rats caused by coal-burning.