Effect of Tea Polyphenols on Nuclear Factor Erythroid 2-related Factor 2 (NRF2) and Kelch-like ECH-associated Protein 1 (KEAP1) Gene Expression in Mice with Acute Cadmium Poisoning.

ABSTRACT

Background:

Cadmium poisoning is mainly caused by inhalation of cadmium dust or cadmium compound dust, which greatly harms people's lives. Tea polyphenols extracted from green tea have wide biological properties, including anti-cardiovascular disease, anti-tumor, anti-inflammatory, and immune regulation. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and Kelch-like ECH-associated protein 1 (KEAP1) are involved in the regulation of cadmium-induced oxidative damage. However, whether tea polyphenols relieve acute cadmium poisoning via regulating NRF2 and KEAP1 gene expression remains unclear.

To explore the influences of tea polyphenols on NRF2 and KEAP1 gene expression in mice with acute cadmium poisoning.

This study was carried out in Zunyi Medical and Pharmaceutical College.

Fifty specific pathogen-free (SPF) male Kunming mice aged 9 weeks, weighing 18-22 g were divided into five groups normal group, model group, low-dose tea polyphenols group, middle-dose tea polyphenols group, and high-dose tea polyphenols group.

Tea polyphenols were administered intraastrically into mice with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg for 10 consecutive days, respectively. Observation indicators (1) liver coefficient, (2) pathological liver injury, (3) liver function, (4) oxidative damage, and (5) NRF2 and KEAP1 gene expression.

The liver coefficient, pathological liver injury, serum aspartate transaminase and alanine transaminase levels of the model group were higher relative to the normal group (P < .05). Relative to the model group, different doses of tea polyphenols treatment significantly relieved liver coefficient, pathological liver injury, serum aspartate transaminase, and alanine transaminase levels (P < .05). Malondialdehyde content in liver tissues of the model group was significantly higher compared to the normal group, while glutathione together with glutathione peroxidase contents of the model group was lower (P < .05). Compared to the model group, malondialdehyde content in liver tissues declined while glutathione together with glutathione peroxidase contents were elevated after different doses of tea polyphenols treatment (P < .05). Relative to the normal group, NRF2 expression in the liver tissues of the model group was significantly lower, while KEAP1 expression was higher (P < .05). Relative to the model group, NRF2 expression in the liver tissues was elevated after treatment of different doses of tea polyphenols, while KEAP1 expression was declined (P < .05).

Tea polyphenols can relieve liver injury in mice with acute cadmium poisoning by regulating NRF2 and KEAP1 expression. Our study might provide a promising treatment strategy for acute cadmium poisoning.