by ME El-Mesery, A El-Mowafy, et al.
August 6, 2009
[Note: To read the full text of this open access article demonstrating that fish oil (DHA) may elicit natural anti-tumor effects superior to those achieved with chemotherapy, click here. Cisplatin is a commonly used chemotherapy drug.]
Background: The fish oil-derived omega-3 fatty acids, like docosahexanoic acid (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model [mice that develop tumors when injected with breast cancer cells], and monitored concomitant changes in:
• Serum levels of C-reactive protein (CRP) [C-reactive protein is a marker of inflammation in the body],
• Lipid peroxidation (measured as malondialdehyde; MDA) [lipid peroxidation is free radical damage to the lipids in cell membranes],
• And leukocytic count (LC) [leukocytic count is white blood cell count; leukocytosis is elevated leukocyte count, associated with infection or inflammatory processes].
Further, we verified the capacity of DHA to ameliorate the lethal, cisplatin-induced nephrotoxicity [kidney damage] in rats and the molecular mechanisms involved therein.
Results:
EAC-bearing mice exhibited markedly elevated leukocytic count (2-fold), C-reactive protein (11-fold) and malondialdehyde levels (2.7-fold).
DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in leukocytic count, C-reactive protein and malondialdehyde levels.
These effects for cisplatin were appreciably lower than those of DHA (250 mg/kg).
Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of cisplatin and boosted its ability to reduce serum C-reactive protein and malondialdehyde levels.
Correlation studies revealed a high degree of positive association between tumor growth and each of C-reactive protein (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for C-reactive protein.
On the other hand, a single cisplatin dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2 to 5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from cisplatin-treated rats displayed significantly elevated MDA- and TNF-?-, but reduced GSH-levels.
Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of cisplatin, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-?-, but increased GSH- levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-? ) r = 0.92) and GSH (r = -0.82); implying causal relationships.
Conclusion:
• DHA elicited prominent chemopreventive effects [interference with cancer progression] on its own,
• And appreciably augmented those of cisplatin as well.
The extent of tumor progression in various mouse groups was highly reflected by C-reactive protein levels (thus implying a diagnostic/prognostic role for C-reactive protein).
Further, this study is the first to reveal that DHA can obliterate the lethal cisplatin-induced nephrotoxicity and renal tissue injury.
At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.
Source: Cell Division, Apr 2, 2009;4(6). PMID: 19341447, by E-Mesery, ME, Al-Gayyar MM, Salem HA, Darweish MM, El-Mowafy AM. Departments of Biochemistry and Pharmacology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. [E-mail:
aelmowafy@yahoo.com]
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