Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N-1-acetyl-transferase gene expression induced by renal ischaemia–reperfusion in rats

Abstract

Renal ischaemia-reperfusion (I/R) is a well-characterised model of acute renal failure that causes both local and remote organ injury. The aim of this work was to investigate the effect of thymoquinone, the main constituent of the volatile oil extracted from Nigella sativa seeds, on renal and hepatic changes after renal ischaemia-reperfusion. Male Sprague-Dawley rats were divided into sham I/R vehicle-treated groups, and I/R thymoquinone-treated groups. Thymoquinone (10 mg/kg, p.o.) was administered for ten consecutive days to the I/R thymoquinone group before injury. I/R and I/R thymoquinone groups were subjected to 30-min ischaemia followed by 4-h reperfusion. I/R resulted in a significant increase in malondialdehyde (MDA) level and decreases in glutathione-S-transferase (GST) and superoxide dismutase (SOD) activity in liver and kidney tissues. Thymoquinone treatment caused the reversal of I/R-induced changes in MDA as well as GST and SOD activity. Moreover, I/R caused a significant rise in creatinine and alanine aminotransferase serum levels. CYP3A1 mRNA expression was induced significantly by I/R in both liver and kidney tissues compared with sham group. Thymoquinone reduced significantly this increase. I/R caused induction of mRNA expression of spermidine/spermine N-1-acetyl-transferase (SSAT), a catabolic enzyme that participates in polyamine metabolism, in liver and kidney tissues. Thymoquinone reduced SSAT mRNA expression significantly in liver and markedly in kidney. These findings suggested that thymoquinone protected against renal I/R-induced damage through an antioxidant mechanism as well as the decrease of CYP3A1 and SSAT gene expression.