Environmental carbon tetrachloride exposure disrupts the liver structure and metabolic detoxification function in mice via p38MAPK/NF-κB/NLRP3 pathway

Abstract

We investigated the effects of carbon tetrachloride (CCl4) exposure on liver detoxification. We confirmed that 0.2%-0.8% CCl4 decreased the liver carboxylesterase (CarE), lactate dehydrogenase (LDH) activity and total protein (TP) levels, while 0.2% and 0.8% CCl4 increased the liver acetylcholine esterase (AChE) activity (P< 0.05). It was observed0.4%-0.8% CCl4 increased serum glutathione S-transferase (GST) and catalase (CAT) activity, 0.1%-0.8% CCl4 increased the level of malondialdehyde (MDA), and 0.2% CCl4 increased the level of total superoxide dismutase (T-SOD). The expression of nod-like receptor protein 3 (NLRP3), interleukin-1β (IL-1β), and tumour necrosis factor-α (TNF-α) were significantly elevated in 0.2%-0.8% CCl4 exposure (P< 0.05). The expression of p38MAPK, gasdermin D (GSDMD), and nuclear factor kappa-B kinase (IKK) was decreased in 0.1%-0.8% CCl4 exposure, while the apoptosis was not statistically different in all groups. This indicates that 0.1% CCl4 exposure could damage the liver structure and detoxification function via p38MAPK/NF-κB/NLRP3 pathway.

Keywords

• Carbon tetrachloride
• liver injury
• antioxidant
• inflammation
• network toxicology