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.

Oregano (Origanum vulgare) Essential Oil and Its Constituents Prevent Rat Kidney Tissue Injury and Inflammation Induced by a High Dose of L-Arginine

“…A slight diminution in the MPO activity can partially be attributed to the impact of thymol on the neutrophil adhesion capacity, which is decreased by exposure to this monoterpene [39]. Furthermore, the anti-inflammatory activity of thymol could be associated with NF-kB and PI3K/Akt signaling pathway attenuation, which was recently discovered in a glycerol-induced AKI model [40]. Interestingly, scarce data are found on the influence of thymol on TNF-α production; however, some of them do suggest the potential of this monoterpene to decrease its production/expression [41].…”

“…Oregano oil monoterpene phenols, thymol, and carvacrol were previously proven to possess a large number of pharmacological activities, including nephroprotective activity [31,40,42,54]. In accordance with previous findings, the results of our study demonstrated that thymol and carvacrol alone or combined significantly reduced serum urea and creatinine levels, as well as kidney tissue NGAL, KIM-1, and inflammatory parameters (NO, MPO, and TNF-α) and decreased CD68 expressing cells infiltration, thus preventing renal damage caused by a high dose of L-arginine.…”

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification

“…SOD and GSH exhibit antioxidant properties and contribute to anti-aging effects. In instances where the kidney generates an excessive amount of superoxide and hydroxyl radicals, the redox equilibrium becomes disrupted, resulting in diminished levels of SOD and GSH and increased levels of MDA, along with diminished tissue antioxidant capacity being observed [25,26]. Inflammatory cytokines TNF-α and IL-6 are swiftly and transiently produced in response to infection and tissue injury [27].…”

Thymol as a Potential Neuroprotective Agent: Mechanisms, Efficacy, and Future Prospects

“…24 Thymol's antioxidant capacity is partly attributed to its ability to regulate the Nrf2 and protein kinase B (AKT) signaling pathways. 29,50,51 Nrf2 is a critical transcription factor that governs the regulation of over 200 genes, including those encoding SOD, CAT, and GPX, to resist oxidative stress. 29,52 In another study, it found that Monarda didyma L. essential oil and thymol supplementation in mice could both significantly upregulate the expressions of Nrf2, and its downstream HO-1, SOD2, and NAD (P)H: quinone oxidoreductase 1(NQO1) proteins, protecting against aging-induced learning and memory impairments and brain oxidative stress damage.…”