Astaxanthin prevents nephrotoxicity through Nrf2/HO-1 pathway

Area of Science:

• Pharmacology
• Toxicology
• Biochemistry

Background:

• Methotrexate (MTX) is a chemotherapy agent with known renal toxicity.
• Oxidative stress plays a critical role in MTX-induced nephrotoxicity.
• Astaxanthin (AST), a natural carotenoid, possesses antioxidant properties.

Purpose of the Study:

• To investigate the protective effects of astaxanthin (AST) against methotrexate (MTX)-induced nephrotoxicity in a rat model.
• To evaluate the impact of AST on oxidative stress markers and the Nrf2/HO-1 pathway in MTX-treated rats.

Main Methods:

• Male Wistar rats were administered MTX and varying doses of AST over 10 days.
• Renal function was assessed by measuring serum creatinine, urea, and uric acid levels.
• Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase, were analyzed.
• The expression of the Nrf2/HO-1 pathway was examined.

Main Results:

• MTX administration led to significant renal histopathological damage and elevated serum creatinine, urea, and uric acid.
• MTX significantly increased kidney tissue MDA levels and decreased SOD and catalase activity.
• AST treatment dose-dependently ameliorated MTX-induced renal dysfunction and oxidative stress.
• AST upregulated Nrf2/HO-1 gene expression and improved antioxidant enzyme activities.

Conclusions:

• Astaxanthin demonstrates significant nephroprotective effects against MTX-induced toxicity in rats.
• AST mitigates MTX-induced renal damage by alleviating oxidative stress and modulating the Nrf2/HO-1 pathway.
• AST holds potential as a therapeutic agent to prevent or treat MTX-related kidney injury.