Effect of spironolactone on cisplatininduced nephrotoxicity in rabbits

Abstract

<jats:p> The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day <jats:sup>1</jats:sup>), oral doses of spironolactone (20.0 mg kg <jats:sup>1</jats:sup>) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P&lt;0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+ cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spiro nolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spiro nolactone significantly (P&lt;0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit. </jats:p>

Carnitine Deficiency Provokes Cisplatin‐Induced Hepatotoxicity in Rats

“…Under similar experimental conditions, our results are in accordance with those reported by Ahmida et al. [29] who demonstrated that cisplatin induced severe nephrotoxicity without any significant changes in liver enzymes or histopathology. On the other hand, our results disagree with the data presented by Zicca et al.…”

Spironolactone but not Eplerenone Exacerbates Cisplatin Nephrotoxicity

“…The impact of MR antagonism on CIS nephrotoxicity is controversial: spironolactone has been reported to exacerbate CIS-induced nephrotoxicity in rabbits (33), whereas eplerenone treatment had a protective effect in balb/c mice (34). Moreover, daily spironolactone administration for one week reduced CIS-induced nephrotoxicity caused by a single CIS injection in Wistar albino rats (35).…”

The effects of zingerone against vancomycin‐induced lung, liver, kidney and testis toxicity in rats: The behavior of some metabolic enzymes

“…In the present study, distilled water was used to dissolve the ZO and VCM. The doses of VCM and ZO were determined based on previous studies, respectively …”