Protective effect of thymol on glycerol-induced acute kidney injury

Abstract

Acute kidney injury (AKI) is a syndrome characterized by an accelerating decrease in renal function in a short time. Thymol is one of the main components of thyme species and has a variety of pharmacological effects. Here, we investigated whether thymol could ameliorate rhabdomyolysis (RM)-induced AKI and its related mechanism. Glycerol was used to induce RM-associated AKI in rats. Rats received thymol (20 mg/kg/day or 40 mg/kg/day) gavage 24 h before glycerol injection until 72 h after injection daily. Kidney injury was identified by measuring serum creatinine (Scr) and urea levels and by H&E and PAS staining and immunohistochemistry (the expression of proliferating cell nuclear antigen (PCNA)). Renal superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress-related Nrf2/HO-1 signaling pathways were measured. The expression of the inflammatory markers TNF-α, IL-6, MCP-1, and NF-κB was assessed by ELISA and western blotting. Finally, the expression of the PI3K/Akt signaling pathway was detected by western blotting. Glycerol administration induced obvious renal histologic damage and increased Scr, urea, and PCNA expression. Notably, thymol treatment attenuated these structural and functional changes and prevented renal oxidative stress, inflammatory damage and PI3K/Akt pathway downregulation associated with glycerol-induced AKI. In conclusion, thymol might have potential applications in the amelioration of AKI via its antioxidant and anti-inflammatory effects and upregulation of the PI3K/Akt signaling pathway.

Keywords:

• Rhabdomyolysis
• AKI
• oxidative stress
• inflammation
• PI3K/Akt

Author contributions

Qinglian Wang and Guanghui Qi: data curation, formal analysis, and writing the original draft. Fajuan Cheng: conceptualization and writing review and editing. Hongwei Zhou: investigation and writing review. Xiaowei Yang: investigation. Xiang Liu and Rong Wang: conceptualization and writing, review, and editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

The project was supported by the Natural Science Foundation of Shandong Province to Xiang Liu [ZR2020MH079] and the National Natural Science Foundation of China [82100791] to Qinglian Wang.