Abstract
Epigallocatechin-gallate (EGCG) and resveratrol (RSVL) are two of the most promising natural medicines. We verified their capacity to ameliorate cisplatin (CP)-induced disruption of renal glomerular filtration rate (GFR) in rats, and sought the mediatory involvement of lipid peroxidation (malondialdehyde [MDA]-level) and inflammatory cytokine (TNF-α) therein. CP (10 mg kg−1), a single i.p. dose, disrupted GFR (11-fold-rise in proteinuria, 2–5-fold rise in serum creatinine/urea levels) after 7 days, and killed all animals after 10 days. Kidney-homogenates from CP-treated rats displayed higher MDA and TNF-α, but lower reduced-glutathione (GSH) levels. Rats treated with EGCG (50 mg kg−1, but not 25 mg kg−1) had no fatalities and showed significantly-recovered GFR; while their kidney-homogenates had markedly reduced MDA, TNF‐α and enhanced GSH levels at 7 days. Conversely, RSVL or quercetin (25, 50 mg kg−1) neither improved GFR nor reduced (MDA)/TNF-α levels after 7 days. Resuming treatment with 50 mg kg−1 for 10 days rescued only 25% of animals (p > 0.05). Correlation studies showed a significant association between creatinine level, and each of MDA (r = 0.91), GSH (r = −0.87), and TNF-α (0.91). The study showed for the first time that EGCG, unlike RSVL, can protect against CP-induced nephrotoxicity. At the molecular level, CP triggers a high level of oxidative stress and systemic inflammation, events that were all abrogated with EGCG; better than RSVL or quercetin.
Acknowledgement
The study was supported by a graduate Mansoura University grant to M. E.-M. (03/2007).