Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides
<p>Abstract</p> <p>Background</p> <p>The fish oil-derived ω-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,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-04-01
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| Series: | Cell Division |
| Online Access: | http://www.celldiv.com/content/4/1/6 |
| _version_ | 1818140182833004544 |
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| author | Darweish MM Salem HA Al-Gayyar MM El-Mesery ME El-Mowafy AM |
| author_facet | Darweish MM Salem HA Al-Gayyar MM El-Mesery ME El-Mowafy AM |
| author_sort | Darweish MM |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The fish oil-derived ω-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 molecular mechanisms involved therein.</p> <p>Results</p> <p>EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/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 (250 mg/kg). Interestingly, DHA (125 mg/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.</p> <p>On the other hand, a single CP 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 (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.</p> <p>Conclusion</p> <p>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 leukocytosis, systemic inflammation, and oxidative stress.</p> |
| first_indexed | 2024-12-11T10:39:55Z |
| format | Article |
| id | doaj.art-1bb8bc28a9494280beb2d284f7bb4f35 |
| institution | Directory Open Access Journal |
| issn | 1747-1028 |
| language | English |
| last_indexed | 2024-12-11T10:39:55Z |
| publishDate | 2009-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj.art-1bb8bc28a9494280beb2d284f7bb4f352022-12-22T01:10:37ZengBMCCell Division1747-10282009-04-0141610.1186/1747-1028-4-6Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxidesDarweish MMSalem HAAl-Gayyar MMEl-Mesery MEEl-Mowafy AM<p>Abstract</p> <p>Background</p> <p>The fish oil-derived ω-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 molecular mechanisms involved therein.</p> <p>Results</p> <p>EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/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 (250 mg/kg). Interestingly, DHA (125 mg/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.</p> <p>On the other hand, a single CP 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 (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.</p> <p>Conclusion</p> <p>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 leukocytosis, systemic inflammation, and oxidative stress.</p>http://www.celldiv.com/content/4/1/6 |
| spellingShingle | Darweish MM Salem HA Al-Gayyar MM El-Mesery ME El-Mowafy AM Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides Cell Division |
| title | Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides |
| title_full | Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides |
| title_fullStr | Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides |
| title_full_unstemmed | Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides |
| title_short | Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides |
| title_sort | chemopreventive and renal protective effects for docosahexaenoic acid dha implications of crp and lipid peroxides |
| url | http://www.celldiv.com/content/4/1/6 |
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