Arsenic trioxide (As2O3) is an effective drug in the treatment of leukaemia and many solid tumours. In clinical trials, arsenic therapy is closely associated with hepatic toxicity. The present study was designed to investigate the efficacy of omega-3 fatty acid against As2O3-induced hepatotoxicity. A 4 mg/kg body weight (bw) of As2O3 was orally administered to Wistar male rats for 45 days. Hepatotoxicity was evaluated by biochemical tests, antioxidant assays and histopathological examinations. Arsenic accumulation was found in the liver tissue of rats treated with As2O3. Hepatoprotective efficacy of omega-3 fatty acid was analysed by the combination therapy with As2O3. In vivo studies revealed a significant rise in lipid peroxidation with concomitant decline in reduced glutathione, glutathione-dependant antioxidant enzymes and antiperoxidative enzymes in the liver tissue of rats treated with arsenic. The supplementation of omega-3 fatty acid at a dose of 50 mg/kg bw with As2O3 offers ameliorative effect against hepatocellular toxicity. Omega-3 fatty acid maintained hepatic marker enzymes, antioxidant enzymes and decreased lipid peroxidation. The combination treatment clearly reduced the hepatic structural abnormalities such as haemorrhage, necrosis and cholangiofibrosis in the rats treated with arsenic. This study concludes that the omega-3 fatty acid might be useful for the protection against As2O3-induced hepatotoxicity.
AebiH (1974). In: BergmeyerHU (ed) Methods of Enzymatic Analysis. VolII. New York, NY: Academic Press, pp. 673–678.
2.
AnandanRAshaKKAmmuK. (2003) Effects of peroxidised PUFA on tissue defense system in experimentally induced myocardial infarction in rats. In: SurendranPKMathewPTThampuranN (eds) Seafood Safety. India: Society of Fisheries Technologists, pp. 330–335.
3.
AposhianHV (1997) Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity. Annual Review of Pharmacology and Toxicology37: 397–419.
4.
BanerjeeNBanerjeeSSenR. (2009) Chronic arsenic exposure impairs macrophage functions in the exposed individuals. The Journal of Clinical Immunology29(5): 582–594.
5.
BarbeyJTSoignetS (2001) Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Annals of Internal Medicine135(9): 842–843.
6.
BeugeJAAustSD (1978) The thiobarbituric acid assay. Methods in Enzymology52: 306–307.
7.
CarterDEAposhianHVGandolfiAJ (2003) The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review. Toxicology and Applied Pharmacology193(3): 309–334.
8.
ChouchaneSSnowET (2001) In vitro effect of arsenical compounds on glutathione-related enzymes. Chemical Research in Toxicology14: 517–522.
9.
DasSSantraALahiriS. (2005) Implications of oxidative stress and hepatic cytokine (TNF-alpha and IL-6) response in the pathogenesis of hepatic collagenesis in chronic arsenic toxicity. Toxicology and Applied Pharmacology204(1): 18–26.
10.
EllmanGL (1959) The sulfhydryl groups. Archives of Biochemistry and Biophysics82(1): 70–77.
11.
El-MowafyAMAl-GayyarMMSalemHA. (2010) Novel chemotherapeutic and renal protective effects for the green tea (EGCG): role of oxidative stress and inflammatory-cytokine signaling. Phytomedicine17(14): 1067–1075.
12.
FloraSJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radical Biology and Medicine51(2): 257–281.
13.
GhoshAMandalAKSarkarS. (2009) Nanoencapsulation of quercetin enhances its dietary efficacy in combating arsenic-induced oxidative damage in liver and brain of rats. Life Sciences84(3–4): 75–80.
14.
GoldbergDMSpoonerRJ (1983) Glutathione reductase. In: BergmeyerHUBergmeyerJGrabiM (eds) Methods of Enzymatic Analysis. 3rd ed. Vol III. Weinheim, Germany: Verlag Chemie, pp. 258–265.
15.
González-PérizAPlanagumàAGronertK. (2006) Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S-hydroxy-DHA. Federation of American Societies for Experimental Biology Journal20(14): 2537–2539.
16.
HabigWHPabstMJJakobyWB (1974) Glutathione S-transferase. The first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry249(22): 7130–7139.
17.
HellerARRösselTGottschlichB. (2004) Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients. International Journal of Cancer111(4): 611–616.
18.
IslamKHaqueAKarimR. (2011) Dose–response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh. Environmental Health10: 64.
19.
KakkarPDasBViswanathanPN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry and Biophysics21(2): 130–132.
20.
KorzhovVIZhadanVN (2003) Effect of omega-3 polyunsaturated fatty acids on activity of glutathione-dependent enzymes in the liver cytosol and blood erythrocytes in rats with experimental chronic bronchitis and in the norm. Ukrainskii Biokhimicheskii Zhurnal75(4): 115–119.
21.
LiuJLuYWuQ. (2008) Mineral arsenicals in traditional medicines: orpiment, realgar, and arsenolite. The Journal of Pharmacology and Experimental Therapeutics326(2): 363–368.
22.
LowryOHRosenbrouchNJFarrAL. (1951) Protein measurement with folin phenol reagent. The Journal of Biological Chemistry193(1): 265–275.
23.
MajumdarSMaitiAKarmakarS. (2012) Antiapoptotic efficacy of folic acid and vitamin B12 against arsenic-induced toxicity. Environmental Toxicology27(6): 351–363.
24.
MandalAKDasSBasuMK. (2007) Hepatoprotective activity of liposomal flavonoid against arsenite-induced liver fibrosis. The Journal of Pharmacology and Experimental Therapeutics320(3): 994–1001.
25.
MillerWHJrSchipperHMLeeJS. (2002) Mechanisms of action of arsenic trioxide. Cancer Research62(14): 3893–3903.
26.
NicolisICurisEDeschampsP. (2009) Arsenite medicinal use, metabolism, pharmacokinetics and monitoring in human hair. Biochimie91(10): 1260–1267.
27.
NiuCYanHYuT. (1999) Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood94(10): 3315–3324.
28.
NuttLKGogvadzeVUthaisangW. (2005) Indirect effects of Bax and Bak initiate the mitochondrial alterations that lead to cytochrome c release during arsenic trioxide-induced apoptosis. Cancer Biology and Therapy4(4): 459–467.
29.
PaulMKKumarRMukhopadhyayAK (2008) Dithiothreitol abrogates the effect of arsenic trioxide on normal rat liver mitochondria and human hepatocellular carcinoma cells. Toxicology and Applied Pharmacology226(2): 140–152.
30.
ProskuryakovSYKonoplyannikovAGGabaiVL (2003) Necrosis: a specific form of programmed cell death. Experimental Cell Research283(1): 1–16.
31.
RaghuKGYadavGKSinghR. (2009) Evaluation of adverse cardiac effects induced by arsenic trioxide, a potent anti-APL drug. Journal of Environmental Pathology, Toxicology and Oncology28(3): 241–252.
32.
RodríguezVMDel RazoLMLimón-PachecoJH. (2005) Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver. Toxicological Sciences84(1): 157–166.
33.
RotruckJTPopeALGantherHE. (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science179(4073): 588–590.
34.
SanzMAGrimwadeDTallmanMS. (2009) Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European leukemia net. Blood113(9): 1875–1891.
35.
SimopoulosAP (1991) Omega-3 fatty acids in health and disease and in growth and development. The American Journal of Clinical Nutrition54(3): 438–463.
36.
SimopoulosAP (2003) Essential fatty acids in health and chronic diseases. Forum of Nutrition56: 67–70.
37.
SinghSRanaSV (2010) Ascorbic acid improves mitochondrial function in liver of arsenic-treated rat. Toxicology and Industrial Health26(5): 265–272.
38.
WangZY (2001) Arsenic compounds as anticancer agents. Cancer Chemotherapy and Pharmacology48(1): S72–S76.
