Neuroprotective Effect of α-Lipoic Acid against Aß25-35-Induced Damage in BV2 Cells.

The prevalence of Alzheimer's disease (AD) is significantly increasing due to the aging world population, and the currently available drug treatments cannot cure or even slow its progression. α-lipoic acid (LA) is a biological factor widely found in spinach and meat and can dissolve in both lipid and aqueous phases. In medicine, LA has been shown to reduce the symptoms of diabetic polyneuropathy, acute kidney injury, cancers, and some metabolism-related diseases. This study to proves that α-lipoic acid (LA) can stabilize the cognitive function of patients with Alzheimer's disease (AD). BV2 cells were divided into control, LA, Aß25-35, and LA + Aß25-35 groups. Cell growth; IL-6, IL-1ß, TNF-α, IFN-γ, SOD, GPx, CAT, ROS, NO, and iNOS secretion; Wnt-related proteins; cell apoptosis; and cell activation were examined. Here, we found that LA could effectively repress apoptosis and changes in the morphology of microglia BV2 cells activated by Aß25-35, accompanied by the inhibition of the inflammatory response induced by Aß25-35. The Wnt/ß-catenin pathway is also involved in preventing Aß25-35-induced cytotoxicity in microglia by LA. We found an inhibitory effect of LA on microglia toxicity induced by Aß25-35, suggesting that a combination of anti-inflammatory and antioxidant substances may offer a promising approach to the treatment of AD.

The neuroprotective effects of alpha-lipoic acid on an experimental model of Alzheimer's disease in PC12 cells.

With the growth of the aging population, the prevalence of Alzheimer's disease (AD) has increased and influenced the work and daily life of AD patients, imposing a heavy burden on society and the patients' families. AD is a progressive disease with a long duration, and the pathogenesis is very complicated. Here, we found that alpha-lipoic acid (LA), an endogenous, naturally synthesized compound, could attenuate amyloid beta fragment (Aß25-35 )-induced PC12 cell toxicity. Aß25-35 treatment largely decreased the viability of PC12 cells, increased reactive oxygen species (ROS) levels, and increased the percentage of apoptotic cells, which were accompanied by changes in the expression of the apoptosis-related genes. Further, the Wnt pathway was inactivated, and the expression of Wnt pathway-related proteins such as Frizzled2, GSK3ß, and phosphorylated GSK3ß were dysregulated after Aß25-35 treatment. LA efficiently attenuated Aß25-35 -induced PC12 cell apoptosis and downregulated the phosphorylation-mediated degradation of ß-catenin as well as GSK3ß. Our results demonstrate that LA rescues Aß25-35 -induced neurocytotoxicity through the Wnt-ß-catenin pathway.

Refined Cumulative Risk Assessment of Pb, Cd, and as in TCM Decoction Based on Bioavailability through In Vitro Digestion/MDCK Cells.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32-72.49% and 4.98-51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were <1, indicating acceptable health risks. Collectively, our innovation on cumulative risk assessment of TCM and TCM decoction provides a novel strategy with the main purpose of improving population health.

Novel bioavailability-based risk assessment of Cd in earthworms and leeches utilizing in vitro digestion/Caco-2 and MDCK cells.

In the present study, the oral bioavailability of cadmium (Cd) in earthworms and leeches was investigated through in vitro physiologically based extraction test (PBET) digestion/Caco2 and MDKC cell models. We are the first to create an innovative assessment strategy which has capacity to offer a more precise evaluation of Cd-associated health risks in traditional animal medicines (TAMs), by combinational usage of bioavailable Cd levels, the duration and frequency of the exposure to TAMs obtained by questionnaire data, as well as safety factor of TAMs. Our data showed that the percentage of bioavailability for Caco-2 cells in earthworms and leeches ranged from 3.29 to 14.17% and 4.32 to 12.61%, respectively. The percentage of bioavailability of MDCK cells in earthworms and leeches ranged from 4.83 to 15.74% and 6.53 to 15.04%, respectively. After adjusting by the bioavailability of Cd to target hazard quotient (THQ), excitingly, our findings manifested that the health risks induced by the ingestion of earthworms and leeches were acceptable in the clinic. Our key findings suggest that bioavailability characterization cannot be ruled out and health risks should be assessed on the basis of the bioavailable Cd levels rather than total levels. Our novel strategy provides insight into the bio-accumulation of Cd in organisms as well as a more realistic and accurate assessment of Cd-associated health risks in TAMs, with the main purpose of improving public health by scientifically using TAMs.

[Safety assessment and effect of new-type drinking water on immunity in mice].

OBJECTIVE: To assess the safety of four kinds new-type drinking water and explore its effect on immunologic function in mice. METHODS: Its acute oral toxicity and Genotoxicity were detected using acute toxicity test, Ames test, micronucleus assay of mice bone marrow cell and mice sperm malformation test. Its effects on cellular, humoral immune function were assessed respectively by metatarsus-thickening method, Jerne-improved slide method. RESULTS: Its acute oral LD50 in mice were greater than 10000mg/kg BW, three genetic toxicity tests showed negative results, the metatarsal injected with SRBC and number of antibody forming cells were no evidently thicker in test group than in control group. CONCLUSION: The result did not indicate the genotoxicity of the four kinds new-type drinking water and they couldn't effect immunologic function in mice.