Novel chemotherapeutic and renal protective effects for the green tea (EGCG): role of oxidative stress and inflammatory-cytokine signaling.
BACKGROUND
The green tea catechin, epigallocatechin-gallate (EGCG) is a superb nature's medicine candidate. We evaluated the chemotherapeutic/chemoenhancing effects of EGCG in mice bearing the solid Ehrlich ascites carcinoma (EAC) tumor, and jointly monitored levels of serum C-reactive protein (CRP), lipid peroxidation (as malondialdehyde: MDA) and leukocytosis (LC). Besides, we verified whether; and how then, EGCG would protect against a devastating CP-induced nephrotoxicity in rats. In particular, renal proinflammatory (TNF-α) and oxidant stress signals have been investigated.


RESULTS
(EAC)-bearing mice displayed elevated serum-LC (2-fold), -CRP (11-fold) and -MDA levels (2.7-fold). EGCG (20, 40 mg/kg) significantly shrank tumors (by 48% and 92%, respectively), and reduced LC, CRP and MDA levels. Such responses for CP were less prominent than those of EGCG (40 mg/kg). Further, EGCG (20 mg/kg) markedly augmented such functional and biochemical responses to CP. Correlation studies showed positive association between tumor size and each of CRP (r=0.97) and LC (r=0.83). Additionally; in rats, CP (10 mg/kg) caused a prominent nephrotoxicity that was manifested as deteriorated glomerular filtration rate (GFR, 2-5-fold rise in serum creatinine/urea levels) after 4 days, and unanimous animal fatalities after 7 days. Kidney homogenates from CP-treated rats showed significantly higher MDA- and TNF-α-, and -depleted GSH levels. Rats treated with EGCG (50 mg/kg, but not 25 mg/kg) devoid the nephrotoxic effects of CP and their consequences; while their homogenates had appreciably lower MDA and TNF-α, and higher GSH levels. Notable correlation was detected between serum creatinine level and each of MDA (r=0.85), TNF-α (r=0.85) and GSH (r=-0.81).


CONCLUSIONS
This study shows remarkable cytotoxic/chemoenhancing effects for EGCG and introduces CRP as a predictor of both tumor's progression and responsiveness to chemotherapy. Further, this study is the first to reveal that EGCG can obliterate the lethal CP-induced nephrotoxicity. Mechanistically, EGCG acts by suppressing leukocytosis, systemic inflammation, oxidative stress, and their sequelae.
El-Mowafy
A M
AM
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. aelmowafy@yahoo.com
Al-Gayyar
M M
MM
Salem
H A
HA
El-Mesery
M E
ME
Darweish
M M
MM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D028241:Camellia sinensis / Q000737:chemistry*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D016207:Cytokines; D010936:Plant Extracts; D012076:Renal Agents; D008315:Malondialdehyde; D002392:Catechin; D002097:C-Reactive Protein; C045651:epigallocatechin gallate; D002945:Cisplatin