Biochanin A Inhibits Colistin-Induced Kidney Injury in Rats via Induction of Nrf2/HO-1/NQO1 Axis

Colistin is a polymyxin glycopeptide antibiotic produced by bacteria known as colistinus, a Bacillus polymixa variant. Despite its deleterious side effects especially on the kidneys, the use of colistin was reconsidered because of its effectiveness against the multi-drug-resistant gram-negative bacilli. Biochanin A (BCA) is an isoflavone phytoestrogen compound with well-known anti-inflammatory, antioxidant and antiapoptotic activities. The current study aimed to investigate the nephroprotective activities of BCA against renal injury induced by colistin. BCA was administered in two dose levels (25 and 50 mg/kg, p.o.) and colistin was injected at a daily dose of 480,000 IU/kg, IP BCA administration guarded against colistin-induced kidney injury as it inhibited the increase in serum levels of creatinine, urea and cystatin C as well as histopathological alterations. In addition, BCA It exhibited antioxidant activities as it ameliorated the increase in renal content of malondialdehyde (MDA) and the reduction in the activities of, superoxide dismutase (SOD), and catalase (CAT). This was associated with modulation of Bax and Bcl-2 mRNA expression so as to antagonize colistin-induced apoptosis. Besides, BCA showed significant anti-inflammatory actions against colistin- induced increase in the immunoreactivity of interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α). Further, BCA enhanced immuno-expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase (NQO1) in colistin-challenged animals. Also, BCA did not have any effects on the antibacterial activity of colistin. In conclusion, BCA significantly attenuates renal injury induced by the antibiotic colistin as evidenced by the reduced serum markers of kidney injury in rats. This can be credited, at least partially, to its antioxidant, antiapoptotic, anti-inflammatory activites as well as induction of Nrf2/HO-1/NQO1 axis.