for RB DHA synergistic with chemo in solid tumor model in mice

[Lani]

Fatty oil in fish may help reduce tumors: study
[Reuters News Service]
LONDON (Reuters) - An omega 3 fatty acid found in fish oils reduced the size of tumors in mice and made a chemotherapy drug more potent while limiting its harmful effects, Egyptian researchers reported on Thursday.
The findings, published in publisher BioMed Central's peer-reviewed Cell Division journal, add to evidence showing a range of health benefits from eating the fatty acids found in foods such as salmon.
A.M. El-Mowafy and colleagues from Mansoura University in Egypt looked at how an omega 3 fatty acid called docosahexanoic acid, or DHA, affected solid tumors growing in mice and how well it interacted with the chemotherapy drug cisplatin.
"Our results suggest a new, fruitful drug regimen in the management of solid tumors based on combining cisplatin and possibly other chemotherapeutics with DHA," El-Mowafy said in a statement.
"DHA elicited prominent chemo-preventative effects on its own, and appreciably augmented those of cisplatin as well."
[...]
In their study, El-Mowafy's team found that, at the molecular level, DHA reduces the accumulation of white blood cells, systemic inflammation, and a harmful condition marked by decreased antioxidant levels — all of which have been linked to tumor growth.
Their experiment also showed that the fatty acid reduced toxicity and injury to kidney tissue caused by the chemotherapy drug, the researchers said.

OPEN ACCESS: EARLY VIEW: Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides
[Cell Division]
Background: The fish oil-derived omega-3 fatty acids, like docosahexanoic (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, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the possible mechanisms involved therein.
Results: EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250mg/kg). Interestingly, DHA (125mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r= 0.85) and leukocytosis (r=0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10mg/kg) induced nephrotoxicity in rats that was evidenced by a disrupted glomerular filtration rate, GFR (2-5-fold rise in serum creatinine/urea levels) after 4days, and globally-induced animal fatalities after 7days. Kidney-homogenates from CP-treated rats displayed significantly-elevated MDA, and -reduced GSH levels. Rats treated with DHA (250mg/kg, but not 125mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA, and -increased GSH levels. Significant association was detected between creatinine level and each of MDA (r= 0.81) and GSH (r=-0.82); thus indicating causal relationships between these biochemical and functional parameters.
Conclusion: DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus, implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing inflammation, leukocytosis, oxidative stress, and by replenishing the endogenous antioxidant machinery.