|Year : 2019 | Volume
| Issue : 7 | Page : 284-290
Galangin ameliorates changes of membrane–bound enzymes in rats with streptozotocin–induced hyperglycemia
Amal A Aloud1, Chinnadurai Veeramani2, Chandramohan Govindasamy2, Mohammed A Alsaif2, Khalid S Al-Numair2
1 Department of Food Sciences and Nutrition, College of Food and Agriculture Sciences, King Saud University, P.O.Box 2460, Riyadh, 11451, Saudi Arabia
2 Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia
|Date of Submission||15-Feb-2019|
|Date of Decision||12-Mar-2019|
|Date of Acceptance||15-Jun-2019|
|Date of Web Publication||05-Jul-2019|
Dr. Chandramohan Govindasamy
Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433
Source of Support: None, Conflict of Interest: None
Objective: To assess the protective effect of galangin on membrane bound enzymes in rats with streptozotocin-induced diabetes.
Methods: A single low dose of streptozotocin was injected to adult male albino rats to induce hyperglycemia. Galangin (8 mg/kg) or glibenclamide 600 μg/kg as a standard drug was given orally once daily for 45 days by gavage. Membrane-bound adenosine triphosphatases were determined including total ATPase, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues (kidney, liver, and heart).
Results: The levels of total ATPases, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues were significantly altered in diabetic rats as compared to that in normal rats. After 45 days of treatment with galangin or glibenclamide, the levels of these enzymes were similar to that of normal control rats.
Conclusions: Oral administration of galangin or glibenclamide can improve activities of these membrane-bound ATPases towards normal levels. Mechanism of galangin needs to be further explored in future.
Keywords: Streptozotocin, Hyperglycemia, Sodium-potassium-ATPase, Calcium-ATPase, Magnesium-ATPase, Galangin
|How to cite this article:|
Aloud AA, Veeramani C, Govindasamy C, Alsaif MA, Al-Numair KS. Galangin ameliorates changes of membrane–bound enzymes in rats with streptozotocin–induced hyperglycemia. Asian Pac J Trop Biomed 2019;9:284-90
|How to cite this URL:|
Aloud AA, Veeramani C, Govindasamy C, Alsaif MA, Al-Numair KS. Galangin ameliorates changes of membrane–bound enzymes in rats with streptozotocin–induced hyperglycemia. Asian Pac J Trop Biomed [serial online] 2019 [cited 2019 Sep 20];9:284-90. Available from: http://www.apjtb.org/text.asp?2019/9/7/284/261764
| 1. Introduction|| |
Diabetes is a chronic progressive disease and one of leading causes of death in developed and developing countries. In the past three decades, the occurrences of type 2 diabetic have augmented dramatically in developing countries. Over time, diabetes causes various complications: It starts by damaging blood vessels, reducing the blood flow, with sequelae that may be macrovascular (heart attack, stroke, and heart failure). About 422 million people have suffered from diabetes worldwide and the number will increase by 418 million in near future. Clinical and epidemiological investigations have confirmed that chronic hyperglycemia and oxidative damages are the major causative factors of diabetes by activating polyol pathway, stimulating glucose auto-oxidation and glycating proteins.
The membrane-bound adenosine triphosphatases play an important role in ion transport across cell membrane, which helps to regulate osmotic pressure, cellular volume and membrane diffusion. Sustained hyperglycemia has generated major causative factor of superoxide anion by glucose autooxidation in chemically induced diabetic rats and diabetic patients. Oxidative injury (superoxide radicals) causes membrane phospholipid peroxidation, resulting in membrane damage and cellular dysfunction. Membrane peroxidation also alters membrane-bound adenosine triphosphatases such as sodium-potassium-ATPase, calcium-ATPase, and magnesium ATPase,.
Food beverage or plants act as major therapeutic agents in modern and traditional medicines. A wide variety of traditional plants products have been used as antidiabetic agents by researchers because they have few side effects and can act as a great auxiliary therapeutic drug. Natural phenolic compound of flavonoids is widely found in plants. Flavonoids have several clinical properties including antidiabetic,, antihypertensiven, anticancer and anti-hepatotoxicity. Galangin is one such bioflavonoid found in Alpinia officinarum. Several medicinal benefits of galangin have been confirmed by researchers that include the hyperglycemic lowering activity, preventive or inhibitory role of cells inflammation, reduction of the tissues or cells damages by anti-oxidant effective role, and inhibition on different types of cancer growth by anti-apoptotic and proliferative effects. Our previous study also confirmed that the galangin had antihyperglycemic and antioxidant properties. It is also reported that galangin could stimulate the ATPase enzyme activities and inhibit H+/K+/ATPase.
Streptozotocin causes insulin deficiency and hyperglycemia by destruction of pancreatic β-cell in animals, and is widely used to establish diabetic animal model. So we selected streptozotocin for modeling in our study. To the best of our knowledge, no studies have been done on the effect of galangin on membrane-bound enzymes. Therefore, our aim was to study the protective effect of galangin on membrane bound enzymes in rats with streptozotocin induced hyperglycemia.
| 2. Materials and methods|| |
Albino Wistar rats (Male only), weighing 180 to 220 g, were brought from Central Animal House, King Saud University. These animals were accommodated in polypropylene cage in air-conditioned room at (25 ± 1) °C and exposed with 12-hour dark-light cycle. The animals were provided (throughout experiments) food ad libitum in normal pellet diet for laboratory use. Rats were treated caringly as per the guidance provided in the Guide for the Care and Use of Laboratory Animals [National Institutes of Health (NIH 85-23; 1985)].
2.2. Chemicals and treated drugs purchasing
Galangin and streptozotocin were acquired from Sigma-Aldrich (St. Louis, MO, U.S.A.). The rest of other used chemicals such as ATP, MgCl2, CaCl2, MgSO4, KCl and NaCl etc. were purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.), laboratory supplier in analytical grade. Glibenclamide is an antidiabetic drug for type 2 diabetic disease. It can improve the insulin activities by protecting the pancreatic cells damages, thereby reducing the higher blood glucose ranges. Hence, glibenclamide was used as a standard drug for this experimental study.
2.3. Hyperglycemia induction in animals
Animals (overnight fasted) were injected (intraperitoneally) with low and single dosage of streptozotocin (40 mg) prepared with 0.1 M citrate buffer (pH 4.5) to induce hyperglycemia. To prevent mortality due to streptozotocin, 20% of glucose was administered for one day. Ninety-six hours after streptozotocin-induction, diabetes was confirmed by estimating the glucose level. Animals with plasma glucose above 180 mg/dL were selected for further experiments.
A total of 42 rats were randomly allocated into seven groups 6 rats per group. In our earlier study where the acute oral toxicity study of galangin was reported and it had no signs of toxicity even at the highest dose of 320 mg/kg. Hence, in this study, galangin at 4, 8 and 16 mg/kg was selected and this drug or glibenclamide at 600 μg/ kg mixed with dimethyl sulfoxide (5%) was given orally once daily for 45 d.
Group I : Control rats received only 5% dimethyl sulfoxide
Group II : Normal rats received 16 mg/kg of galangin
Group III : Hyperglycemic rats
Group IV : Hyperglycemic rats received 4 mg/kg of galangin
Group V : Hyperglycemic rats received 8 mg/kg of galangin
Group VI : Hyperglycemic rats received 16 mg/kg of galangin
Group VII : Hyperglycemic rats received 600 μg/kg of glibenclamide
Before treatment of 0th day and after treatment of 45th day, the body weight was calculated by using normal weighing balance. After 45 days of treatment, rats were fasted for 12 h, then anaesthetized by 24 mg/kg ketamine (intramuscular injection) and sacrificed by cervical dislocation. Blood sample was received in EDTA tube for the assessment of glucose by using available glucose kit (Trinder reagent Kit method).
2.5. Grouping for further study
Thirty rats were randomly separated into five groups (each group having 6 rats). Galangin at 8 mg/kg or 600 μg/kg glibenclamide (mixed with dimethyl sulfoxide 5%) was treated daily once for 45 d. The 8 mg/kg of galangin showed optimized activity of glucose lowering than other two doses such as 4 and 16 mg/kg. Hence, this active dose of 8 mg/kg was used for further experiments.
Group I : Normal (5% dimethyl sulfoxide)
Group II : Normal plus 8 mg/kg of galangin
Group III : Hyperglycemic rats
Group IV : Hyperglycemic plus 8 mg/kg of galangin
Group V : Hyperglycemic plus 600 μg/kg of glibenclamide
After 45 days of treatment, rats were fasted for 12 h, then sacrificed by cervical dislocation. Blood collected and erythrocytes were isolated as the following procedure. The buffy coat was collected after the plasma isolation and then the white cells were detached. The remaining section of erythrocytes was thoroughly cleaned with physiological saline. Afterwards, erythrocyte was lysed with hypotonic phosphate buffer at pH 7.4. The hemolysate was isolated by 2 500 rpm centrifugation for 10 min and the supernatant was used for the measurement of membrane bound ATPases. Moreover, liver, kidney and heart were collected for the measurement of membrane bound ATPases.
2.6. Biochemical assays
Plasma glucose was measured by the Trinder reagent kit method. Total protein from tissues was measured by Lowry et al method. Erythrocytes, liver, kidney and heart total ATPase activity was measured using Evans method, and sodium-potassium-ATPase activity based on Bonting method. Moreover, calcium-ATPase and magnesium-ATPase activities were determined by Hjerten and Pan and Ohnishi et al, respectively.
2.7. Statistical analysis
Results were calculated by one-way analysis (ANOVA) of Duncan’s multiple range test (DMRT) with the commercially available statistical analysis SPSS software (9.05). Results were expressed as mean ± SD. P values < 0.05 were considered significant.
| 3. Results|| |
3.1. Effect of galangin on glucose and body weight
Body weight was decreased and plasma glucose increased in rats with streptozotocin-induced hyperglycemia. Meanwhile, galangin or glibenclamide improved these alterations to almost normal level. Rats treated with 8 mg/kg of galangin showed the better result of glucose and body weight than the other two doses [Figure 1].
|Figure 1: Effect of galangin on body weight (A: 0th day) and (B: 45th day) and plasma glucose (C: 0th day) and (D: 45th day) in diabetic rats. Values are expressed as mean ± SD (n=6). a,b,c,d,e,fValues not sharing same superscript differ significantly at P<0.05 by Duncan’s Multiple Range Test.|
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3.2. Effect galangin on ATPase activities
[Figure 2], [Figure 3], [Figure 4], [Figure 5] show that activities of total ATPase, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in tissues (liver, kidney, and heart) and erythrocytes all decreased in rats with streptozotocin-induced hyperglycemia. But galangin or glibenclamide significantly increased the activity of these enzymes.
|Figure 2: Effect of galangin on the activity of total ATPases in diabetic rats. Values are expressed as mean ± SD (n=6). Values not sharing a common superscript differ significantly at P<0.05 by Duncan’s Multiple Range Test. *-μmol of Pi liberated per hour. GLMD: glibenclamide.|
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|Figure 3: Effect of galangin on the activity of Na+/K+-ATPase in diabetic rats. Values are expressed as mean ± SD (n=6). a,b,cValues not sharing a common superscript differ significantly at P<0.05 by Duncan’s Multiple Range Test. *-μmol of Pi liberated per hour. GLMD: glibenclamide.|
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|Figure 4: Effect of galangin on the activity of Ca2+-ATPase in diabetic rats. Values are expressed as mean ± SD (n=6). a,b,cValues not sharing a common superscript differ significantly at P<0.05 by Duncan’s Multiple Range Test. *-μmol of Pi liberated per hour. GLMD: glibenclamide.|
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|Figure 5: Effect of galangin on the activity of Mg2+-ATPase in diabetic rats. Values are expressed as mean ± SD (n =6). a,b,cValues not sharing a common superscript differ significantly at P<0.05 by Duncan’s Multiple Range Test. *-μmol of Pi liberated per hour. GLMD: glibenclamide.|
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| 4. Discussion|| |
Chronic hyperglycemia accompanied by insulin resistance with or without insulin deficiency (type-2 diabetics) is associated with many diabetic complications as an outcome of oxidative damage to organs. Increased oxidative stress and reduced antioxidants occur during diabetes by glucose autoxidation and protein glycosylation,. Sodium-potassium-ATPase, calcium-ATPase, and magnesium-ATPase play a major role in the maintenance of ion transport, electrolyte balance and cell volume regulations,. The membrane-bound adenosine triphosphatases activities (i.e. Na+/K+, Ca2+, Mg2+- ATPase) are shown to be altered in the hyperglycemic state due to membrane lipid peroxidation. Erythrocytes and tissues are more sensitive to peroxidative damage due to high content of unsaturated fatty acid in membrane. Hence, membrane bound ATPases have been used as markers for hyperglycemic damage.
Sodium-potassium-ATPase moves two potassium ions into cell and carries three sodium ions out of the cell, which played an important role in cellular homeostasis. Insulin plays an active role in biosynthesis of sodium-potassium-ATPase. A recent study has reported that the sodium potassium-ATPase activity decreases significantly in liver, heart and erythrocytes of chemically- induced hyperglycemia in rats. The cellular membrane damage caused by free radicals results in reduction of sodium-potassium- ATPase activity. Reduced activity of sodium-potassium-ATPase may contribute to the pathophysiology of diabetic complicated risks. Oxidation of thiol groups is abundant in sodium-potassium- ATPase, which could be involved in control of sodium-potassium- ATPase activity. Lipid and protein changes in the cellular membrane caused sodium-potassium-ATPase activity in chronic hyperglycemic patients. In this current study, decreased activity of sodium-potassium-ATPase was observed in chemically streptozotocin- induced hyperglycemia in rats. Treatment with galangin and glibenclamide brought sodium-potassium-ATPase activity towards normalcy, by insulin secretion effect and/or by preventing damage to membrane lipids by oxidative stress. Moreover, Gupta et al have discovered that insulin treatment with chronic hyperglycemic state partially restored sodium-potassium-ATPase activity.
Calcium and magnesium ATPases are found in cellular membranes, which are dependable for preserving calcium gradient. Further, insulin plays an important role for regulating cellular Ca2+ involving Ca2+-Mg2+-ATPase. Ca2+-Mg2+-ATPase is involved in the Ca2+ reabsorption in proximal tubules. Ca2+ and Mg2+-ATPases activities were significantly decreased in experimental diabetic rats. The results of this finding are consistent with previous report. This decreased enzymes’ activity could be due to reduced secretion or action of insulin, which regulates these enzymes. Further, increased lipid peroxidation also could have diminished the activity of Ca2+ and Mg2+-ATPases in uncontrolled high blood glucose status. Oral therapy of galangin and glibenclamide had restored the Ca2+ and Mg2+-ATPases activities towards normal levels. Thus improved ATPase activity could be due to it increased secretion or activity of insulin, reduced membrane phospholipids damages and improved glycaemic control.
Galangin treatment enhanced the functions of total ATPase, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in diabetic rats, which could be attributed to enhanced insulin secretion, antioxidant status and the glucose lowering activity. In our previous reports, we claimed that galangin significantly lowered the glucose and increased the insulin secretion in diabetic rats. Antioxidant is a therapeutic agent for many disorders complication including diabetes, hypertension and cancer. It’s also associated with the protective effect on abnormal ATPase activities through the diminished oxidative stress in streptozotocin induced diabetic rats. Galangin with the antioxidant potential possibly decreases the membrane lipid peroxides. Our previous study showed the galangin acts as a potent antioxidant in diabetic rats. The active metabolites of galangin such as kaempferol and quercetin are identified by in vitro studies, which could be responsible for the several biological effects including anti-diabetic, anti-oxidant and membrane bound enzyme activities.
In conclusion, galangin ameliorates membrane-bound ATPase changes in tissues (liver, kidney, and heart) and erythrocytes in diabetic rats. Mechanism of galangin could be further evaluated in future.
Conflict of interest statement
The authors declare that there is no conflict of interest.
| References|| |
Bajaj HS, Zinman B. Glucose lowering strategies for cardiac benefits: Pathophysiological mechanisms. Physiology (Bethesda)
2018; 33(3): 197-210.
Reddy PM, Philip GH. Changes in the levels of respiration and ions in the tissues of freshwater fish, under fenvalerate stress. Chemosphere
1992; 25(6): 843-852.
Chang KC, Chung SY, Chong WS, Suh JS, Kim SH, Noh HK, et al. Possible superoxide radical-induced alteration of vascular reactivity in aortas from streptozotocin-treated rats. J Pharmacol Exp Ther
1993; 266(2): 992-1000.
Jain SK. Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem
1989; 264(35): 21340-21345.
Rauchová H, Ledvinková J, Kalous M, Drahota Z. The effect of lipid peroxidation on the activity of various membrane-bound ATPases in rat kidney. Int J Biochem Cell Biol
1995; 27(3): 251-255.
Yessoufou A, Gbenou J, Grissa O, Hichami A, Simonin AM, Tabka Z, et al. Anti-hyperglycemic effects of three medicinal plants in diabetic pregnancy: Modulation of T cell proliferation. BMC Complement Altern Med
2013; 13: 77.
Tiwari BK, Kumar D, Abidi AB, Rizvi SI. Efficacy of composite extract from leaves and fruits of medicinal plants used in traditional diabetic therapy against oxidative stress in alloxan-induced diabetic rats. ISRN Pharmacol
2014; 2014: 608590.
Michael HN, Salib JY, Eskander EF. Bioactivity of diosmetin glycosides isolated from the epicarp of date fruits, Phoenix dactylifera
, on the biochemical profile of alloxan diabetic male rats. Phytother Res
2013; 27(5): 699-704.
Duarte J, P
érez-Palencia R, Vargas F, Ocete MA, P
érez-Vizcaino F, Zarzuelo A, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol
2001; 133(1): 117-124.
Su CH, Kuo CL, Lu KW, Yu FS, Ma YS, Yang JL, et al. Fisetin-induced apoptosis of human oral cancer SCC-4 cells through reactive oxygen species production, endoplasmic reticulum stress, caspase-, and mitochondria-dependent signaling pathways. Environ Toxicol
2017; 32(6): 1725-1741.
Akachi T, Shiina Y, Ohishi Y, Kawaguchi T, Kawagishi H, Morita T, et al. Hepatoprotective effects of flavonoids from shekwasha (Citrus depressa)
against D-galactosamine-induced liver injury in rats. J Nutr Sci Vitaminol
2010; 56(1): 60-67.
Aloud AA, Veeramani C, Govindasamy C, Alsaif MA, El Newehy AS, Al-Numair KS. Galangin, a dietary flavonoid, improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin- induced diabetic rats. Redox Rep
2017; 22(6): 290-300.
Jung YC, Kim ME, Yoon JH, Park PR, Youn HY, Lee HW, et al. Antiinflammatory effects of galangin on lipopolysaccharide-activated macrophages via
ERK and NF-κB
pathway regulation. Immunopharmacol Immunotoxicol
2014; 36(6): 426-432.
Sivakumar AS, Anuradha CV. Effect of galangin supplementation on oxidative damage and inflammatory changes in fructose-fed rat liver. Chem Biol Interact
2011; 193(2): 141-148.
Lei YF, Chen JL, Zhang WT, Fu W, Wu GH, Wei H, et al. In vivo
investigation on the potential of galangin, kaempferol and myricetin for protection of D-galactose-induced cognitive impairment. Food Chem
2012; 135(4): 2702-2707.
Murakami S, Muramatsu M, Otomo S. Inhibition of gastric H+, K(+)- ATPase by quercetin. J Enzym Inhib
1992; 5(4): 293-298.
Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res
2001; 50(6): 537-546.
Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem
1969; 6(1): 24-27.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem
1951; 193(1): 265-275.
Evans DJ Jr. Membrane adenosine triphosphatase of Escherichia coli:
Activation by calcium ion and inhibition by monovalent cations. J Bacteriol
1969; 100(2): 914-922.
Bonting SL. Sodium-potassium activated adenosine-triphosphatase and cation transport. In: Bittar C (ed). Membrane and iron transport
. London: Wiley Interscience ;1970, p. 25-28.
Hjertén S, Pan H. Purification and characterization of two forms of a low-affinity Ca2+
-ATPase from erythrocyte membranes. Biochim Biophys Acta
1983; 728(2): 281-288.
Ohnishi T, Suzuki T, Suzuki Y, Ozawa K. A comparative study of plasma membrane Mg2+
-ATPase activities in normal, regenerating and malignant cells. Biochim Biophys Acta
1982; 684(1): 67-74.
Aronson D, Rayfield EJ. How hyperglycemia promotes atherosclerosis: Molecular mechanisms. Cardiovasc Diabetol
2002; 1: 1.
Yan LJ. Pathogenesis of chronic hyperglycemia: From reductive stress to oxidative stress. J Diabetes Res
2014; 2014: 137919.
Suhail M. Na, K-ATPase: Ubiquitous multifunctional transmembrane protein and its relevance to various pathophysiological conditions. J Clin Med Res
2010; 2(1): 1-17.
Haynes DH. Mechanism of Ca2+
transport by Ca2+
-ATPase pump: Analysis of major states and pathways. Am J Physiol
1983; 244(1): G3- 12.
Namazi G, Jamshidi Rad S, Attar AM, Sarrafzadegan N, Sadeghi M, Naderi G, et al. Increased membrane lipid peroxidation and decreased Na+
-ATPase activity in erythrocytes of patients with stable coronary artery disease. Coron Artery Dis
2015; 26(3): 239-244.
Vér A, Szántó I, Bányász T, Csermely P, Végh E, Somogyi J. Changes in the expression of Na+
-ATPase isoenzymes in the left ventricle of diabetic rat hearts: Effect of insulin treatment. Diabetologia
1997; 40(11): 1255-1262.
Sweeney G, Klip A. Regulation of the Na+
-ATPase by insulin: Why and how? Mol Cell Biochem
1998; 182(1-2): 121-133.
Al-Numair KS, Veeramani C, Alsaif MA, Chandramohan G. Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharm Biol
2015; 53(9): 1372-1378.
Davis SM, Maddux AB, Alonso GT, Okada CR, Mourani PM, Maahs DM. Profound hypokalemia associated with severe diabetic ketoacidosis. Pediatr Diabetes
2016; 17(1): 61-65.
Goldberg IJ. Diabetic dyslipidemia: Causes and consequences. J Clin Endocrinol Metab
2001; 86(3): 965-971.
Gupta S, Phipps K, Ruderman NB. Differential stimulation of Na+ pump activity by insulin and nitric oxide in rabbit aorta. Am J Physiol
1996; 270(4 Pt 2): H1287-H1293.
van Heeswijk MP, Geertsen JA, van Os CH. Kinetic properties of the ATP-dependent Ca2+
pump and the Na+
exchange system in basolateral membranes from rat kidney cortex. J Membr Biol
1984; 79(1): 19-31.
Hope-Gill HF, Nanda V. Stimulation of calcium ATPase by insulin, glucagon, cyclic AMP and cyclic GMP in Triton X-100 extracts of purified rat liver plasma membrane. Horm Metab Res
1979; 11(12): 698-700.
Levy J, Rempinski D, Kuo TH. Hormone-specific defect in insulin regulation of (Ca2+
)-adenosine triphosphatase activity in kidney membranes from streptozocin non-insulin-dependent diabetic rats. Metab Clin Exp
1994; 43(5): 604-613.
Jain SK, Lim G. Lipoic acid decreases lipid peroxidation and protein glycosylation and increases (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-treated human erythrocytes. Free Radic Biol Med
2000; 29(11): 1122-1128.
Otake Y, Walle T. Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9. Drug Metab Dispos
2002; 30(2): 103-105.
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