Background Chronic low lead poisoning affects human health; especially when liver is experiencing inflammatory and fatty infiltration, it removes less lead and the damage aggravates, which may be related to cell apoptosis.
Objective This study is designed to investigate the effects of low lead on hepatocyte apoptosis in rats with non-alcoholic fatty liver disease (NAFLD), and clarify the role of low lead in liver damage.
Methods After two weeks of adaptive feeding, 60 rats were randomly divided into four groups:normal diet group, low Pb group, high fat diet group, and low Pb+high fat diet group, with 15 rats in each group. They were sacrificed after feeding with corresponding diet plans for eight weeks. Liver and blood samples were collected to detect blood and liver lead levels, liver function indicesaspartate transaminase (AST) and alanine transaminase (ALT), and antioxidant indicessuperoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and total antioxidant capacity (T-AOC), as well as to observe liver pathological alteration under light microscope. The protein and mRNA expressions of Bax, bcl-2, P53, and Fas were measured by Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively.
Results The levels of blood lead and liver lead in the low Pb group and the low Pb+high fat diet group were significantly higher than those in the normal diet group (P < 0.05), and the levels in the low Pb+high fat diet groupblood lead:(0.31±0.10) mg/L; liver lead:(3.37±1.12)mg/L were significantly higher than those in the low Pb groupblood lead:(0.26±0.10)mg/L; liver lead:(2.42±0.87)mg/L (P < 0.05). The results of HE staining showed that cells on rat liver in the normal diet group were closely arranged with uniform nucleus size; the low Pb group did not show obvious damage; the high fat diet group and the low Pb+high fat diet group showed fat vacuoles, especially the low Pb+high fat diet group, indicating an established rat model of NAFLD. For AST and ALT, the low Pb group, the high fat diet group, and the low Pb+high fat diet group showed higher levels than the normal diet group (P < 0.05); the high fat diet group and the low Pb+high fat diet group showed higher levels than the low Pb group (P < 0.05); the low Pb+high fat diet group showed higher levels than the high fat diet group (P < 0.05). Compared with the normal diet group, the low Pb group had no differences in SOD, GSH, T-AOC, and MDA, but the high fat diet group and the low Pb+high fat diet group showed reduced SOD, GSH, and T-AOC (P < 0.05) and increased MDA (P < 0.05). Compared with the low Pb group, the high fat diet group and the low Pb+high fat diet group showed decreased SOD, GSH, and T-AOC (P < 0.05) and increased MDA (P < 0.05). Compared with the high fat diet group, the low Pb+high fat diet group showed reduced SOD, GSH, and T-AOC (P < 0.05) and elevated MDA (P < 0.05). According to the results of Western blot and RT-PCR, the expressions of P53, Fas, and Bax between the normal diet group and the low Pb group were not different; but the high fat diet group and the low Pb+high fat diet group showed significantly higher levels of the expressions than the normal diet group and the low Pb group (P < 0.05), and the low Pb+high fat diet group (protein expression levels of p53, Fas, and Bax were 1.57±0.14, 1.16±0.08, and 1.34±0.12, respectively; mRNA expression levels were 3.35±0.14, 2.52±0.08, and 2.25±0.06, respectively) showed significantly higher levels of the expressions than the high fat diet group (protein expression levels of p53, Fas, and Bax were 1.35±0.10, 0.98±0.06, and 1.15±0.09, respectively; mRNA expression levels were 2.75±0.16, 1.82±0.04, and 1.72±0.05, respectively) (P < 0.05). The expressions of bcl-2 protein between the normal diet group and the low Pb group were not different, but the high fat diet group (0.52±0.05) and the low Pb+high fat diet group (0.50±0.04) showed significantly lower levels than the normal diet group (1.18±0.04) and the low Pb group (1.14±0.03) (P < 0.05), and there was no difference between the low Pb+high fat diet group and the high fat diet group; the low Pb group showed significantly lower level of expression of bcl-2 mRNA than the other three groups (P < 0.05).
Conclusion Low lead can exacerbate liver dysfunction and decrease antioxidant capacity in rats with NAFLD, which may be related to aggravated hepatocyte apoptosis induced by low lead.
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