Epigallocatechin-3-gallate in combination with corticosteroids mitigates heat stress-induced acute kidney injury through modulating heat shock protein 70 and toll-like receptor 4-dependent pathways.

ABSTRACT

Recently, recurrent heat stress (HS) and dehydration have been exhibited to give rise to kidney disease epidemic in hot regions. The current study was carried out to estimate a possible renoprotective effect of dexamethasone (Dexa) and epigallocatechin-3-gallate (EGCG) as a heat shock protein (HSP)-70 inhibitor on HS-induced nephropathy. In total, five groups of rats were used control group, HS group (exposed to heat for 40 min), Dexa+HS group (rats were injected with Dexa i.p.15 mg/kg/day for 3 days followed by HS), EGCG+HS group (rats received EGCG 100 mg/kg/day, orally, for 7 days followed by HS), and EGCG+ Dexa +HS group (rats received EGCG 100 mg/kg/day, orally, for 7 days and injected Dexa as described along the last 3 days followed by HS). Kidney sections were stained with H&E and scored for tubular injury. A marked increase in creatinine, urea, malondialdehyde (MDA), monocyte chemoattractant protein (MCP)-1, HSP-70, nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR-4) and Caspase-3 expression was observed after HS induction (p < 0.001). Treatment with EGCG combined with Dexa notably reduced tubular injury, MCP-1, HSP-70, NF-κB, and TLR-4 levels (p < 0.001). Moreover, it increased IL-10, antioxidant capacity and Bcl-2 expression levels in the kidney (p < 0.001). This renoprotective impact might be attributed to anti-inflammatory, antioxidant, and anti-apoptotic mechanisms besides interfering with TLR-4-mediated NF-κB activation pathway.