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

• Published in: Phytotherapy research Vol. 37; no. 8; pp. 3559 - 3571
• Main Authors: Shafeek, Faten, El‐Kashef, Dalia H., Abu‐Elsaad, Nashwa, Ibrahim, Tarek
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.08.2023; Wiley Subscription Services, Inc
• Subjects: Antioxidants; Apoptosis; Caspase; Corticoids; Corticosteroids; Creatinine; Dehydration; Dexamethasone; Dual energy X-ray absorptiometry; EGCG; Epidemics; Epigallocatechin gallate; Heat shock proteins; Heat stress; Heat tolerance; Hsp70 protein; Inflammation; Injury prevention; Kidney diseases; Kidneys; MCP‐1; Monocyte chemoattractant protein; Monocytes; Nephropathy; NF‐κB; Receptors; Temperature effects; TLR‐4; Urea; NF-κB; heat stress; MCP-1; TLR-4; EGCG
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.7834

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.