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Outline
Based on the broad-spectrum targeted lipid group and metabolomics technology, the mechanism of citric acid (CA) antagonizing benzo[a]pyrene (B[a]P)-induced renal injury in mice was explored, which provided a new idea for the intervention of renal injury after B[a]P exposure.
Forty-eight healthy 4-week-old male C57BL/6 mice were randomly allocated into six groups, namely the control group, low/medium/high-dose B[a]P groups (2.5, 5, 10 mg/kg), citric acid group (400 mg/kg), and high-dose B[a]P+citric acid group, with 8 mice per group. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for the detection of broad-spectrum targeted lipid profiling and metabonomics in renal tissues, and the contents of serum creatinine, serum uric acid and blood urea in renal samples were quantified. Pathological changes of the kidney were examined using HE staining.
The concentrations of creatinine, uric acid and urea in the kidney of the exposed mice increased (represented by peak area), and the urea concentration in the high-dose group (3 935 000±1 043 140.86) was significantly higher than that in the control group (2 706 250±385 484.39) (P<0.05). The renal pathological results of B[a]P exposure group were damaged, and the high-dose damage was serious. Compared with the control group, a total of 114 differential metabolites were identified in the kidney tissues of mice in the B[a]P high exposure group, which were mainly enriched in 32 metabolic pathways such as arachidonic acid, glutathione, and sphingolipids. After the intervention of citric acid, the renal creatinine, uric acid and urea concentrations in the high-dose B[a]P+citric acid group (10 625 750±6 541 890.63, 1 042 907.5±692 189.5, 1 849 501.25±1 150 570.62) were significantly lower than those in the high-dose group (19 150 000±3 523 796.65, 1 985 000±363 396.67, 3 935 000±1 043 140.86) (P<0.05), and the renal pathological damage was improved. Further omics studies showed that 106 differential metabolites were identified in the high-dose B[a]P+citric acid group compared with the high-dose B[a]P group, and 48 significantly reversed metabolites such as leukotriene B4, 15-hydroxyeicosatetraenoic acid, hydroxyproline, indoxyl sulfate, corticosterone, cytidine, guanylate and coenzyme Q10 were found in the intersection of differential metabolites in the high-dose B[a]P group. It was mainly enriched in arachidonic acid metabolism, steroid hormone biosynthesis, histidine, glutathione, arginine and proline, primary bile acid biosynthesis, taurine and hypotaurine, pyrimidine, purine, tyrosine, sphingolipid and unsaturated fatty acid biosynthesis and other metabolic pathways.
Citric acid can antagonize subchronic B[a]P-induced renal injury in mice by inhibiting inflammatory response, enhancing antioxidant capacity, regulating hormone and bile acid levels such as aldosterone and cortisol, and repairing energy and lipid metabolism homeostasis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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