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

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-?B), 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-?B, 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-?B activation pathway.

Automated summary

Recently, recurrent heat stress and dehydration have caused a kidney disease epidemic in hot regions. This study investigated the potential renoprotective effect of dexamethasone and epigallocatechin-3-gallate on heat stress-induced nephropathy. The results showed that combination treatment with EGCG and Dexa significantly reduced kidney injury and inflammatory and oxidative stress responses.