ABSTRACT
This study aimed to investigate the effect and possible mechanism of carnosic acid (CA) on delaying aging. The effects of CA on senescence-related β-galactosidase (SA-β-Gal) activity and expressions of p53, p21 and p16 were evaluated by an oxidative challenge induced premature 2BS cell senescence model. Meanwhile, the animal experiment was approved by the Ethics Committee of Zhejiang Hospital. Male C57 BL/6J mice were injected with 100 mg·kg-1·d-1 D-galactose (D-gal) for 8 weeks to establish an aging model in vivo, and CA at 5 and 10 mg·kg-1·d-1 were given ig administration at the same time. Morris water maze test was used to test the spatial memory ability. Then the serum and tissue samples were collected for the detections of malondialdehyde (MDA), total superoxide dismutase (T-SOD), interleukin-6 (IL-6), tumor necrosis factor α (TNFα) and advanced glycation end products (AGEs) as well as the protein expression of p53, p21 and p16 in hippocampus of brain. The results showed that H2O2 induced increment of SA-β-Gal activity (95%) was prevented by CA treatment (35%) and the enhanced protein expressions of p53, p21 and p16 in H2O2 exposed 2BS cells were alleviated by CA treatment, suggesting a potent protective role of CA against premature senescence induced by oxidative challenge. For in vivo study, D-gal induced declined spatial memory ability was partly reversed by CA administration. Besides, the serum and cerebral levels of MDA, IL-6, TNFα and AGEs were attenuated by CA treatment when compared to those in model mice. And the protein expressions of p53, p21 and p16 in mice hippocampus were suppressed by CA in D-gal treated mice. Taken together, our results showed that CA protects premature senescence induced by oxidative stress and D-gal, which is related to its antioxidative, antiinflammatory roles and inhibition on non-enzymatic glycosylation.
ABSTRACT
This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.