Telmisartan Exacerbates Cisplatin-Induced Nephrotoxicity in a Mouse Model

Area of Science:

• Nephrology
• Pharmacology
• Oncology

Background:

• Cisplatin (CDDP) is a vital chemotherapy drug, but its use is limited by nephrotoxicity.
• Factors like lower blood pressure and renin-angiotensin system (RAS) inhibitors may worsen CDDP-induced kidney damage, though mechanisms are unclear.

Purpose of the Study:

• To investigate the impact of hypotensive drugs, including RAS inhibitors and calcium channel blockers, on CDDP-induced nephrotoxicity in mice.
• To determine if blood pressure changes correlate with the severity of CDDP-induced kidney damage.

Main Methods:

• BALB/c mice were administered CDDP alone or in combination with amlodipine, enalapril, telmisartan, or losartan.
• Nephrotoxicity was assessed by measuring serum creatinine (CRE) and blood urea nitrogen (BUN) levels.
• Renal fibrosis and apoptosis were evaluated using Masson's trichrome and TUNEL staining, respectively.

Main Results:

• Serum CRE and BUN levels significantly increased in mice treated with CDDP plus enalapril, losartan, or telmisartan compared to CDDP alone.
• The CDDP + amlodipine group showed an increasing trend in serum CRE and BUN.
• Significant renal fibrosis was observed in the CDDP + telmisartan group.
• No correlation was found between changes in CRE/BUN levels and changes in systolic blood pressure.

Conclusions:

• RAS inhibitors, particularly telmisartan, exacerbate CDDP-induced nephrotoxicity in mice.
• The exacerbation of nephrotoxicity is not directly correlated with changes in systolic blood pressure.
• These findings highlight potential risks associated with combining CDDP chemotherapy with RAS inhibitors.