Troxerutin, a Bioflavonoid, Improves Oxidative Stress in Blood of Streptozotocin-Induced Type-1 Diabetic Rats Troxerutin improves oxidative stress in diabetic rats
Iranian Journal of Pharmaceutical Sciences,
Vol. 13 No. 2 (2017),
1 April 2017
,
Page 75-86
https://doi.org/10.22037/ijps.v13.40699
Abstract
Type 1 diabetes is a chronic disease characterized by the body's inability to produce insulin due to destruction of the beta cells. There is increasing evidence that reactive oxygen species (ROS) play a major role in the development of diabetic complications. The purpose of this study is to investigate the effects of troxerutin administration on oxidative stress markers in blood of STZ-induced diabetic rats. Male Wistar rats were divided into 4 groups as: control (con), control-troxerutin (CON-TRX), diabetes (Dia), diabetic-troxerutin (DIA-TRX). Type 1 diabetes was induced by injection of streptozotocin (STZ) (i.p, 55mg/kg) and lasted for 10 weeks. Animals received oral administration of troxerutin (150 mg/kg) for 4 weeks. At the end of study, malondialdehyde (MDA, the main product of lipid peroxidation), activity of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were measured spectrophotometrically. Induction of diabetes with STZ resulted in increased MDA levels and decreased blood antioxidant capacity as compared with those of controls (P<0.05). Pre-treatment of diabetic rats with troxerutin significantly decreased the levels of MDA (P<0.01) and increased the activity of antioxidant enzymes SOD, GPX, and CAT compared to untreated-diabetic groups. Troxerutin had no significant influence on non-diabetic rats. These findings showed that troxerutin may prevent oxidative complications of diabetic circumstances by elevating antioxidant enzymes activities and reducing lipid peroxidation.
Keywords:
- diabetes
- troxerutin
- oxidative stress
- antioxidant
- malondialdehyde
- superoxide dismutase
- glutathione peroxidase
- catalase
How to Cite
Reza badalzadeh, Leila Chodari, & Vajihe ghorbanzadeh. (2017). Troxerutin, a Bioflavonoid, Improves Oxidative Stress in Blood of Streptozotocin-Induced Type-1 Diabetic Rats: Troxerutin improves oxidative stress in diabetic rats. Iranian Journal of Pharmaceutical Sciences, 13(2), 75–86. https://doi.org/10.22037/ijps.v13.40699
References
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[18] Zhang Z-F, Fan S-H, Zheng Y-L, Lu J, Wu D-M, Shan Q, et al. Troxerutin improves hepatic lipid homeostasis by restoring NAD+-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice.Biochemical pharmacology (2014) 91(1):74-86.
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[20] Badalzadeh R, Mohammadi M, Yousefi B, Faranjia S, Najafi M, Mohammadi S. Involvement of Glycogen Synthase Kinase-3β and Oxidation Status in the Loss of Cardioprotection by Postconditioning in Chronic Diabetic Male Rats.Adv Pharm Bull (2015) 5(1).
[21] Pari L, Monisha P, Jalaludeen AM. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats.European journal of pharmacology (2012) 691(1):143-150.
[22] Ghyasi R, Sepehri G, Mohammadi M, Badalzadeh R, Ghyasi A. Effect of mebudipine on oxidative stress and lipid peroxidation in myocardial ischemic-reperfusion injury in male rat.Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences (2012) 17(12):1150.
[23] Badalzadeh R, Yavari R, Chalabiani D. Mitochondrial ATP-sensitive K (+) channels mediate the antioxidative influence of diosgenin on myocardial reperfusion injury in rat hearts.General physiology and biophysics (2015).
[24] Aebi H. [13] Catalase in vitro.Methods in enzymology (1984) 105:121-126.
[25] Dave G, Kalia K. Hyperglycemia induced oxidative stress in type-1 and type-2 diabetic patients with and without nephropathy.Cell Mol Biol (Noisy-le-grand) (2007) 53(5):68-78.
[26] Nishikawa T, Edelstein D, Du XL, Yamagishi S-i, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature (2000) 404(6779):787-790.
[27] Santini SA, Marra G, Giardina B, Cotroneo P, Mordente A, Martorana GE, et al. Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM.Diabetes (1997) 46(11):1853-1858.
[28] Bonnefont-Rousselot D. Glucose and reactive oxygen species.Current Opinion in Clinical Nutrition & Metabolic Care (2002) 5(5):561-568.
[29] Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy.Diabetes care (2003) 26(5):1589-1596.
[30] Tanaka Y, Gleason CE, Tran POT, Harmon JS, Robertson RP. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants.Proceedings of the National Academy of Sciences (1999) 96(19):10857-10862.
[31] Adam B, Pentz R, Siegers C, Strubelt O, Tegtmeier M. Troxerutin protects the isolated perfused rat liver from a possible lipid peroxidation by coumarin.Phytomedicine (2005) 12(1):52-61.
[32] Lu J, Wu D-m, Zheng Y-l, Hu B, Cheng W, Zhang Z-f, et al. Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress.The Journal of Immunology (2013) 190(7):3466-3479.
[33] Zhang Z-f, Fan S-h, Zheng Y-l, Lu J, Wu D-m, Shan Q, et al. Troxerutin protects the mouse liver against oxidative stress-mediated injury induced by D-galactose.Journal of agricultural and food chemistry (2009) 57(17):7731-7736.
[34] Panat NA, Maurya DK, Ghaskadbi SS, Sandur SK. Troxerutin, a plant flavonoid, protects cells against oxidative stress-induced cell death through radical scavenging mechanism.Food chemistry (2016) 194:32-45.
[35] Ping X, Junqing J, Junfeng J, Enjin J. Radioprotective effects of troxerutin against gamma irradiation in mice liver.International journal of radiation biology (2012) 88(8):607-612.
[36] Dröge W. Free radicals in the physiological control of cell function.Physiological reviews (2002) 82(1):47-95.
[37] Lee PJ, Choi AM. Pathways of cell signaling in hyperoxia.Free Radical Biology and Medicine (2003) 35(4):341-350.
[38] Shan Q, Lu J, Zheng Y, Li J, Zhou Z, Hu B, et al. Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by D-galactose.BioMed Research International (2009) 2009.
[39] Wu D-m, Lu J, Zheng Y-l, Zhou Z, Shan Q, Ma D-f. Purple sweet potato color repairs D-galactose-induced spatial learning and memory impairment by regulating the expression of synaptic proteins.Neurobiology of learning and memory (2008) 90(1):19-27.
[40] Elangovan P, Pari L. Ameliorating effects of troxerutin on nickel-induced oxidative stress in rats.Redox Report (2013) 18(6):224-232.
[41] Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, et al. Troxerutin improves hepatic lipid homeostasis by restoring NAD(+)-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice.Biochem Pharmacol (2014) 91(1):74-86.
[42] Lu J, Wu D-m, Hu B, Cheng W, Zheng Y-l, Zhang Z-f, et al. Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system.Neurobiology of learning and memory (2010) 93(2):157-164.
[43] Vanessa Fiorentino T, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.Current pharmaceutical design (2013) 19(32):5695-5703.
[44] Patel H, Chen J, Das KC, Kavdia M. Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC.Cardiovasc Diabetol (2013) 12(1):142.
[45] Ramana KV, Friedrich B, Srivastava S, Bhatnagar A, Srivastava SK. Activation of nulcear factor-κB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase.Diabetes (2004) 53(11):2910-2920.
[46] Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications.Circulation research (2010) 106(8):1319-1331.
[47] Zhang Z-F, Zhang Y-q, Fan S-H, Zhuang J, Zheng Y-L, Lu J, et al. Troxerutin protects against 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion.Journal of hazardous materials (2015) 283:98-109.
[2] King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections.Diabetes care (1998) 21(9):1414-1431.
[3] Brownlee M. Biochemistry and molecular cell biology of diabetic complications.Nature (2001) 414(6865):813-820.
[4] Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited.Arteriosclerosis, thrombosis, and vascular biology (2004) 24(5):816-823.
[5] Jain SK. Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells.Journal of Biological Chemistry (1989) 264(35):21340-21345.
[6] Jain SK, Levine SN, Duett J, Hollier B. Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats.Metabolism (1990) 39(9):971-975.
[7] Maritim A, Sanders R, Watkins rJ. Diabetes, oxidative stress, and antioxidants: a review.J Biochem Mol Toxicol (2003) 17(2438.26).
[8] Mehta JL, Rasouli N, Sinha AK, Molavi B. Oxidative stress in diabetes: a mechanistic overview of its effects on atherogenesis and myocardial dysfunction.The international journal of biochemistry & cell biology (2006) 38(5):794-803.
[9] Li G, Chen Y, Saari JT, Kang YJ. Catalase-overexpressing transgenic mouse heart is resistant to ischemia-reperfusion injury.American Journal of Physiology-Heart and Circulatory Physiology (1997) 273(3):H1090-H1095.
[10] Vinod BS, Maliekal TT, Anto RJ. Phytochemicals as chemosensitizers: from molecular mechanism to clinical significance.Antioxidants & Redox Signaling (2013) 18(11):1307-1348.
[11] Wang Y, Liu Y, Xu S, Liu Y, Yang P, Du S, et al. Determination and modelling of troxerutin solubility in eleven mono-solvents and (1, 4-dioxane+ 2-propanol) binary solvents at temperatures from 288.15 Kto 323.15 K.The Journal of Chemical Thermodynamics (2017) 104:138-149.
[12] Fan S-h, Zhang Z-f, Zheng Y-l, Lu J, Wu D-m, Shan Q, et al. Troxerutin protects the mouse kidney from d-galactose-caused injury through anti-inflammation and anti-oxidation.International immunopharmacology (2009) 9(1):91-96.
[13] Gohel MS, Davies AH. Pharmacological agents in the treatment of venous disease: an update of the available evidence.Current vascular pharmacology (2009) 7(3):303-308.
[14] Kessler M, Ubeaud G, Walter T, Sturm F, Jung L. Free radical scavenging and skin penetration of troxerutin and vitamin derivatives.Journal of dermatological treatment (2002) 13(3):133-141.
[15] Geetha R, Yogalakshmi B, Sreeja S, Bhavani K, Anuradha CV. Troxerutin suppresses lipid abnormalities in the heart of high-fat–high-fructose diet-fed mice.Molecular and cellular biochemistry (2014) 387(1-2):123-134.
[16] Lu J, Wu D-m, Zheng Z-h, Zheng Y-l, Hu B, Zhang Z-f. Troxerutin protects against high cholesterol-induced cognitive deficits in mice.Brain (2011):awq376.
[17] Sampath S, Karundevi B. Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat.Molecular and cellular biochemistry (2014) 395(1-2):11-27.
[18] Zhang Z-F, Fan S-H, Zheng Y-L, Lu J, Wu D-M, Shan Q, et al. Troxerutin improves hepatic lipid homeostasis by restoring NAD+-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice.Biochemical pharmacology (2014) 91(1):74-86.
[19] Fraga CG, Leibovitz BE, Tappel AL. Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: characterization and comparison with homogenates and microsomes.Free Radical Biology and Medicine (1988) 4(3):155-161.
[20] Badalzadeh R, Mohammadi M, Yousefi B, Faranjia S, Najafi M, Mohammadi S. Involvement of Glycogen Synthase Kinase-3β and Oxidation Status in the Loss of Cardioprotection by Postconditioning in Chronic Diabetic Male Rats.Adv Pharm Bull (2015) 5(1).
[21] Pari L, Monisha P, Jalaludeen AM. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats.European journal of pharmacology (2012) 691(1):143-150.
[22] Ghyasi R, Sepehri G, Mohammadi M, Badalzadeh R, Ghyasi A. Effect of mebudipine on oxidative stress and lipid peroxidation in myocardial ischemic-reperfusion injury in male rat.Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences (2012) 17(12):1150.
[23] Badalzadeh R, Yavari R, Chalabiani D. Mitochondrial ATP-sensitive K (+) channels mediate the antioxidative influence of diosgenin on myocardial reperfusion injury in rat hearts.General physiology and biophysics (2015).
[24] Aebi H. [13] Catalase in vitro.Methods in enzymology (1984) 105:121-126.
[25] Dave G, Kalia K. Hyperglycemia induced oxidative stress in type-1 and type-2 diabetic patients with and without nephropathy.Cell Mol Biol (Noisy-le-grand) (2007) 53(5):68-78.
[26] Nishikawa T, Edelstein D, Du XL, Yamagishi S-i, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature (2000) 404(6779):787-790.
[27] Santini SA, Marra G, Giardina B, Cotroneo P, Mordente A, Martorana GE, et al. Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM.Diabetes (1997) 46(11):1853-1858.
[28] Bonnefont-Rousselot D. Glucose and reactive oxygen species.Current Opinion in Clinical Nutrition & Metabolic Care (2002) 5(5):561-568.
[29] Ceriello A. New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy.Diabetes care (2003) 26(5):1589-1596.
[30] Tanaka Y, Gleason CE, Tran POT, Harmon JS, Robertson RP. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants.Proceedings of the National Academy of Sciences (1999) 96(19):10857-10862.
[31] Adam B, Pentz R, Siegers C, Strubelt O, Tegtmeier M. Troxerutin protects the isolated perfused rat liver from a possible lipid peroxidation by coumarin.Phytomedicine (2005) 12(1):52-61.
[32] Lu J, Wu D-m, Zheng Y-l, Hu B, Cheng W, Zhang Z-f, et al. Troxerutin Counteracts Domoic Acid–Induced Memory Deficits in Mice by Inhibiting CCAAT/Enhancer Binding Protein β–Mediated Inflammatory Response and Oxidative Stress.The Journal of Immunology (2013) 190(7):3466-3479.
[33] Zhang Z-f, Fan S-h, Zheng Y-l, Lu J, Wu D-m, Shan Q, et al. Troxerutin protects the mouse liver against oxidative stress-mediated injury induced by D-galactose.Journal of agricultural and food chemistry (2009) 57(17):7731-7736.
[34] Panat NA, Maurya DK, Ghaskadbi SS, Sandur SK. Troxerutin, a plant flavonoid, protects cells against oxidative stress-induced cell death through radical scavenging mechanism.Food chemistry (2016) 194:32-45.
[35] Ping X, Junqing J, Junfeng J, Enjin J. Radioprotective effects of troxerutin against gamma irradiation in mice liver.International journal of radiation biology (2012) 88(8):607-612.
[36] Dröge W. Free radicals in the physiological control of cell function.Physiological reviews (2002) 82(1):47-95.
[37] Lee PJ, Choi AM. Pathways of cell signaling in hyperoxia.Free Radical Biology and Medicine (2003) 35(4):341-350.
[38] Shan Q, Lu J, Zheng Y, Li J, Zhou Z, Hu B, et al. Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by D-galactose.BioMed Research International (2009) 2009.
[39] Wu D-m, Lu J, Zheng Y-l, Zhou Z, Shan Q, Ma D-f. Purple sweet potato color repairs D-galactose-induced spatial learning and memory impairment by regulating the expression of synaptic proteins.Neurobiology of learning and memory (2008) 90(1):19-27.
[40] Elangovan P, Pari L. Ameliorating effects of troxerutin on nickel-induced oxidative stress in rats.Redox Report (2013) 18(6):224-232.
[41] Zhang ZF, Fan SH, Zheng YL, Lu J, Wu DM, Shan Q, et al. Troxerutin improves hepatic lipid homeostasis by restoring NAD(+)-depletion-mediated dysfunction of lipin 1 signaling in high-fat diet-treated mice.Biochem Pharmacol (2014) 91(1):74-86.
[42] Lu J, Wu D-m, Hu B, Cheng W, Zheng Y-l, Zhang Z-f, et al. Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system.Neurobiology of learning and memory (2010) 93(2):157-164.
[43] Vanessa Fiorentino T, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases.Current pharmaceutical design (2013) 19(32):5695-5703.
[44] Patel H, Chen J, Das KC, Kavdia M. Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC.Cardiovasc Diabetol (2013) 12(1):142.
[45] Ramana KV, Friedrich B, Srivastava S, Bhatnagar A, Srivastava SK. Activation of nulcear factor-κB by hyperglycemia in vascular smooth muscle cells is regulated by aldose reductase.Diabetes (2004) 53(11):2910-2920.
[46] Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications.Circulation research (2010) 106(8):1319-1331.
[47] Zhang Z-F, Zhang Y-q, Fan S-H, Zhuang J, Zheng Y-L, Lu J, et al. Troxerutin protects against 2, 2′, 4, 4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion.Journal of hazardous materials (2015) 283:98-109.
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