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. 2021 May 27;11(6):1556.
doi: 10.3390/ani11061556.

Acute and Subchronic Toxicity Studies of Aristolochic Acid A in Tianfu Broilers

Dan Xu  1 , Chonglin Ran  2 , Lizi Yin  2 , Juchun Lin  2 , Hualin Fu  2 , Xi Peng  2 , Xiaoling Zhao  1 , Gang Shu  2
Affiliations

Acute and Subchronic Toxicity Studies of Aristolochic Acid A in Tianfu Broilers

Dan Xu et al. Animals (Basel). .

Abstract

Aristolochic acid (AA) is one of the components of some traditional Chinese medicines, which has high toxic potential in animals, leading to huge economic losses in the breeding industry. The purpose of this study is to evaluate the toxicology of AA on Tianfu broilers through acute and subchronic toxicity tests. The results showed that the median lethal dose of AA to Tianfu broilers was 14.52 mg/kg. After continuous intraperitoneal injection of AA solution (1.452 mg/kg) for 28 days, the swollen and necrotic renal tubular epithelial cells were histologically observed; in addition, blood urea nitrogen (BUN) and creatinine (Cre) were significantly increased, indicating AA could induce serious kidney lesions in broilers. Moreover, the ROS, the apoptosis rate and the depolarization rate of the mitochondrial membrane potential of broilers' renal cells increased. The results of QRT-PCR showed that AA reduced the mRNA expressions of HO-1, NQO1, Raf-1 and Bcl-2, while the expressions of Bax and Caspase-3 increased, which show that AA aroused oxidative stress and promoted the apoptosis of renal cells. In conclusion, AA has been found to damage broilers' kidneys by breaking the redox balance to form oxidative stress, along with promoting apoptosis of renal cells.

Keywords: Tianfu broiler; aristolochic acid; kidney; oxidative stress; subchronic toxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structural of aristolochic acid A.
Figure 2
Figure 2
Renal morphology in different groups. (A) CG group; (B) LAG group; (C) MAG group; (D) HAG group.
Figure 3
Figure 3
Kidney index of broilers in different groups. * p < 0.05, compared with the control group (CG).
Figure 4
Figure 4
Effects of aristolochic acid A on renal function of Tianfu broilers. * p < 0.05, compared with the control group (CG). BUN: blood urea nitrogen (μmol/L), Cre: creatine (mmol/L).
Figure 5
Figure 5
Pathological section of the kidney in different groups. (A) CG group; (B) LAG group; (C) MAG group; (D) HAG group. * Cell swelling. Blue circle: karyopyknosis. Blue triangle: karyorrhexis. Black quadrilateral: karyolysis. Red circle: all epithelial cells in a renal tubule were necrotic and shed from the basal layer. H.E. stain, on the left, magnification 200×; the right, magnification 400×.
Figure 6
Figure 6
Effects of aristolochic acid A on the antioxidant system of Tianfu broilers. * p < 0.05, compared with the control group. (CG). MDA: malondialdehyde (mmol/L), SOD: superoxidase dismutase (U/mL), GSH: glutathione (μmol/g) and ROS: Reactive oxygen species (%).
Figure 7
Figure 7
Comparison of mitochondrial membrane potential and apoptosis rate of renal cells in each group. * p < 0.05, compared with the control group (CG).
Figure 8
Figure 8
The mRNA expression of genes (NQO1, HO-1, Raf-1, Caspase 3, Bax and Bcl-2) of renal cells in each group. * p < 0.05, compared with the control group (CG).
Figure 9
Figure 9
Schematic diagram of the possible mechanism of AA-induced renal injury in Tianfu broilers. The toxicological mechanism of AA-induced renal injury contains excessive apoptosis and oxidative stress damage.
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