SIRT-1 activation by quercetin opposes the actions of three transcription factors: p53, ATF4, and NF-κB in a renal ischaemia reperfusion injury in rats

OBJECTIVE: Renal ischaemia reperfusion (I/R) injury is considered one of the main causes of acute kidney injury which can happen because of kidney transplantation surgeries. Renal I/R injury usually leads to activated inflammatory response, accumulating reactive oxygen species, and eventually, leading to apoptosis. METHODS: The rats were randomly divided into five groups (n = 6), sham, I/R, where the rats were subjected to a surgery performing bilateral renal I/R, two different does were given of Quercetin (Q), 50 mg and 100 mg, for 10 days before I/R surgery; however, EX527, a selective silent information regulator 1 (SIRT-1) inhibitor, was given with the former does in the last group, where it was administered 1 hr. after Q injection each day of the mentioned 10 days. KEY FINDINGS AND CONCLUSIONS: The results showed that Q preserved the kidney functions from via acting as antioxidant by upregulating the superoxide dismutase and SLC7A11 levels, downregulating the inflammatory markers, NF-κB, TNF-α, as well as suppressing ATF4/CHOP, and p53/miR34-a/p66Shc/caspase 3 apoptotic pathways. However, the use of EX527 showed a surge of the inflammatory and apoptotic responses and a depletion of renal antioxidant capacity; thus, reversing the observed protective actions to suggest the significant role of SIRT-1 activation by Q, still potential off-targets actions of the former cannot be excluded.