Full
Outline
To evaluate the protective effects of α-ketoglutarate (AKG) on oxidative damage induced by D-galactose (D-gal) in rats and explore its potential mechanisms.
Male SD rats were used as experimental subjects. Oxidative stress injury was induced by intraperitoneal injection of D-gal solution, and the animals were randomly divided into 5 groups: Control group, model group, low-dose AKG group (AKG-L, 50 mg/kg),medium-dose AKG group (AKG-M, 100 mg/kg) and high-dose AKG group (AKG-H, 200 mg/kg). Rats were administered the respective treatment once daily for 4 weeks. The levels of oxidative biomarkers, including malondialdehyde (MDA), protein carbonyls, as well as antioxidant indicators and enzymes such as catalase (CAT),superoxide dismutase (SOD) and reduced glutathione (GSH), were determined using colorimetric assays in plasma and liver tissues. Histopathological examinations were conducted to assess the protective effects of AKG against D-gal-induced oxidative damage. Furthermore, 16S rRNA sequencing and ultra performance liquid chromatography-tandem mass spectrometry were performed to analyze gut microbiota composition and short-chain fatty acids levels in each group, in order to investigate the potential antioxidant mechanisms of AKG.
Compared with the model group, AKG administration significantly reduced MDA and protein carbonyl levels in plasma and liver, while partially enhancing the activities of SOD and CAT as well as GSH levels. Additionally, AKG could modulate the structure of gut microbiota and increase the relative abundance of Lachnospiraceae NK4A136 group, Prevotella and Clostridia vadinBB60 group. Compared with the control group, the levels of the short‑chain fatty acids valeric acid, butyric acid and isobutyric acid in the intestines of rats with oxidative damage were significantly reduced. Following AKG intervention, the levels of these 3 kinds of short‑chain fatty acids were markedly increased, with butyric acid and isobutyric acid showing the most pronounced improvement (P<0.01),approaching those of the normal control group.
AKG exerts a significant protective effects against D-gal-induced oxidative damage in rats. This protective effect is accompanied by improvements in gut microbiota composition and short‑chain fatty acid levels. These findings suggest that the gut microbiota-short‑chain fatty acid axis and antioxidant effects may jointly contribute to the protective action of α‑ketoglutarate.
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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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