Studies on the protective effect of flaxseed oil on cisplatin-induced hepatotoxicity

January 1, 2012 Human Health and Nutrition Data 0 Comments

Studies on the protective effect of flaxseed oil on cisplatin-induced hepatotoxicity

Year: 2012
Authors: Naqshbandi, A. Khan, W. Rizwan, S. Khan, F.
Publication Name: Human & Experimental Toxicology
Publication Details: DOI: 10.1177/0960327111432502


Cisplatin (CP) is known as one of the most potent chemotherapeutic antitumor drugs. The tissue-specific toxicity of CP in the kidneys is well documented. However, at higher doses less common toxic effects such as hepatotoxicity may arise. Since CP remains one of the most effective antineoplastic drug used in chemotherapy, strategies to protect tissues against CP toxicity are of clinical interest. Recently, n3 polyunsaturated fatty acids (PUFAs) from certain plants/seeds notably flaxseed have shown numerous health benefits. In view of this, the present study investigates the protective effect of flaxseed oil (FXO) on CP-induced damage in liver. Rats were pre-fed normal diet and the diet rich in FXO for 10 days and then a single dose of CP (6 mg/kg body weight) was administered intraperitoneally while still on diet. Serum/urine parameters, enzymes of carbohydrate metabolism and oxidative stress were analyzed. CP caused perturbation of the antioxidant defense as reflected by the decrease in the activities of catalase, superoxide dismutase and glutathione peroxidase. Further the activities of various enzymes involved in glycolysis, tricarboxylic acid cycle, gluconeogenesis and hexose monophosphate shunt pathways were determined and were found to be differentially altered by CP treatment. However, these alterations were ameliorated in CP-treated rats fed on FXO. Present results show that dietary supplementation of FXO in CP-treated rats ameliorated CP-induced hepatotoxic and other deleterious effects due to its intrinsic biochemical/antioxidant properties.(Authors abstract)
Recent studies have suggested that hepatotoxicity is also a major dose limiting side effect in CP-based chemotherapy. CP chemotherapy induces a fall in plasma antioxidant levels, which may reflect a failure of the antioxidant defense mechanism against oxidative damage induced by commonly used antitumor drugs. Dietary fish oil (FO) supplementation has been shown to ameliorate gentamicin and CP-induced damage to kidney and liver, respectively. Dietary supplementation with flaxseed oil (FXO) affects the biochemistry of fatty acid metabolism and thus the balance of proinflammatory mediators and atherogenic lipids, holding promise for modulating inflammatory diseases. The present work was undertaken to study the detailed biochemical events/cellular response/mechanisms of CP-induced hepatotoxicity and its protection by dietary FXO.  It was hypothesized that FXO would prevent CP-induced hepatotoxicity due to its intrinsic biochemical and antioxidant properties that would lead to improved metabolism and antioxidant defense mechanism of the liver. The results obtained indicate that dietary supplementation with FXO markedly ameliorated CP-induced adverse effects in liver. The activities of carbohydrate metabolism, membrane and antioxidant enzymes were markedly enhanced by FXO feeding to CP-administered rats. These studies support a potential therapeutic use of CP and FXO combination in combating cancer without hepatotoxic and other harmful side effects. The present results show that CP administration to control rats caused hepatotoxicity as indicated by elevated levels of transaminases (ALT and AST). Scr and BUN were also enhanced with significant decrease in creatinine clearance. These results also show a significant decrease in serum glucose, Pi, PLs and serum cholesterol, accompanied by massive proteinuria, glucosuria and phosphaturia. FXO diet given prior to and following CP administration prevented CP-induced alterations in various serum/urine parameters. Dietary supplementation of FXO prior to and following CP treatment prevented CP elicited increase in levels of Scr, BUN and trans aminases. Serum glucose, PLs and phosphate were improved upon CP treatment to FXO fed rats. The activities of various enzymes involved in glycolysis, tricarboxylic acid (TCA) cycle, gluconeogenesis and hexosemonophosphate (HMP) shunt pathways were differentially altered by CP treatment and/or by FXO consumption. CP caused significant increase in LDH and decrease in MDH which was accompanied with a simultaneous increase in HK activity in liver tissue. FXO administration to CP-treated rats resulted in the overall improvement of carbohydrate metabolism as evident by higher activities of MDH and gluconeogenic enzymes in CPFXO as compared to CP group. FXO might have lowered the number of damaged mitochondria or other affected macromolecules or may have increased the number of normally active organelles or macromolecules. CP enhanced LPO, an indicator of tissue injury and depleted protein thiols. The protection against CP by FXO can be attributed to its intrinsic biochemical and natural antioxidant properties. It appears that FXO enriched with n3 fatty acids enhanced resistance to free radical attack generated by CP administration. The authors conclude that while CP elicited deleterious hepatotoxic effects by causing severe damage to the plasma membrane, mitochondria and other organelles by suppressing antioxidant defense mechanism, however these effects were ameliorated by dietary supplementation with FXO.  FXO may be effective dietary supplementation to maximize the clinical use of CP in the treatment of various malignancies without hepatotoxic and other side effects.  (Editors comments)

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