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2014 ; 1
(ä): 12-30
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Epigallocatechin gallate supplementation protects against renal injury induced by
fluoride intoxication in rats: Role of Nrf2/HO-1 signaling
#MMPMID28962222
Thangapandiyan S
; Miltonprabu S
Toxicol Rep
2014[]; 1
(ä): 12-30
PMID28962222
show ga
Fluoride intoxication generates free radicals, causing oxidative stress that
plays a critical role in the progression of nephropathy. In the present study, we
hypothesized that epigallocatechin gallate (EGCG), found in green tea, protects
the kidneys of rats treated with fluoride by preventing oxidative stress,
inflammation, and apoptosis. Pretreatment of fluoride-treated rats with EGCG
resulted in a significant normalization of creatinine clearance and levels of
urea, uric acid, and creatinine. Fluoride intoxication significantly increased
renal oxidative stress markers and decreased the levels of renal enzymatic and
non-enzymatic antioxidants. In addition, renal NO, TNF-?, IL-6 and NF-?B were
also increased in the renal tissue of fluoride-treated rats. Further, EGCG
pretreatment produced a significant improvement in renal antioxidant status and
reduced lipid peroxidation, protein carbonylation and the levels of inflammatory
markers in fluoride-treated kidney. Similarly, mRNA and protein analyses showed
that EGCG pretreatment normalized the renal expression of Nrf2/Keap1 and its
downstream regulatory proteins in fluoride-treated rat kidney. EGCG also
effectively attenuated fluoride-induced renal apoptosis by the up-regulation of
anti-apoptotic proteins such as Bcl-2 and down-regulation of Bax, caspase-3,
caspase-9 and cytochrome c. Histology and immunohistochemical observations of
Kim-1 provided further evidence that EGCG effectively protects the kidney from
fluoride-mediated oxidative damage. These results suggest that EGCG ameliorates
fluoride-induced oxidative renal injury by activation of the Nrf2/HO-1 pathway.