A comparative investigation of the nephrotoxic effects of various antihypertensive drugs in rats: biochemical and histopathological analysis

Abstract

Aims: Hypertension is known to cause potentially fatal kidney damage. However, it is unclear whether long-term use of antihypertensive drugs establishes any toxic effect on the kidney. This study investigate whether clonidine, methyldopa, rilmenidine, amlodipine and ramipril establish nephrotoxic effects in rats. Materials and methods: Methyldopa, clonidine, rilmenidine, amlodipine and ramipril were administered orally to rat groups for three months. At the end of that period, rats were sacrificed by decapitation, the kidneys extracted and biochemical and histopathological analyses performed. Results: the experimental results revealed that methyldopa and ramipril slightly increased Malondialdehyde (MDA) and Myeloperoxidase (MPO) levels in rat kidney tissue and slightly reduced total glutathione (GSH). Rilmenidine increased MDA and MPO levels more than methyldopa and ramipril, but less than clonidine and amlodipine. Severe glomerular cellularity, hyalinization, tubulointerstitial inflammation and tubular necrosis were encountered in the clonidine and amlodipine groups, in which MDA and MPO were highest and GSH lowest. These histopathological findings were moderate in the rilmenidine group and mild in the methyldopa and ramipril groups. in addition to these histopathological findings, mild interstitial fibrosis and increased mesenchymal matrix were observed in the amlodipine group and increased mesenchymal matrix alone in the clonidine group. Conclusions: Ramipril and methyldopa were identified as drugs causing mild nephrotoxicity, rilmenidine moderate nephrotoxicity and amlodipine and clonidine severe nephrotoxicity.