Abstract
Purpose
Diabetes leading to the production and circulation of glycation products along with the reduction of the activity of glyoxalase-I (GLO-I) contribute to diabetic nephropathy. Therefore, we studied the effect of 1,8 cineole (Cin) on the formation of diverse glycation products and the activity of GLO-I as well as renal histopathological alterations in the type-2 diabetic rat.
Methods
Type 2 diabetes was induced in rats with a combination of streptozotocin and nicotinamide (55 + 200 mg/kg). Two groups of rats, normal and diabetic, were treated intragastrically with Cin (200 mg/kg) once daily for 2 months. Fasting blood sugar, insulin resistance index, lipid profile, the activity of GLO-I, glycation products (Glycated albumin, Glycated LDL, Methylglyoxal, and advanced glycation end products), and oxidative stress (Advanced oxidation protein products, malondialdehyde, oxidized LDL, and reduced glutathione), inflammatory markers (Tumor necrosis factor-α and Transforming growth factor-1β), creatinine in the serum (Cre), and proteinuria (PU) in the urine of all rats was determined as well as renal histopathological alterations were investigated.
Results
Cin reduced biochemical (Cre and PU) and histopathological (glomerulosclerosis) indicators of renal dysfunction in the diabetic rat compared to untreated diabetic rats. Moreover, the treatment decreased different glycation, oxidative stress, and pro-inflammatory markers (p < 0.001). Further, Cin had an advantageous effect on glucose and lipid metabolism.
Conclusions
Cin ameliorated diabetic nephropathy via reduction of TGF-1β following to decrease the formation of different glycation products, oxidative stress, and inflammatory process with the induction of the activity of glyoxalase-I in type 2 diabetic rats.
Keywords: 1,8 cineole; Diabetic nephropathy; Glycation; Glyoxalase-I; TGF-1β
Highlights
1- The effect of 1,8 cineole on histopathological and biochemical parameters in type-2 diabetic rats has been represented
2- We reported the beneficial effect of cineole on the activity of Glo-I for the first time
3- In our study for the first time the advantageous effect of cineole on early to end glycation products and oxidative stress and inflammatory markers has been shown.
Introduction
Diabetic kidney disease (DKD) or diabetic nephropathy (DN) a kind of chronic kidney disease (CDK) is a prevalent complication of diabetes to cause end-stage renal disease (ESRD) worldwide [1]. Diabetes leading to the production and circulation of glycated albumin (g-Alb) [2], methylglyoxal (MGO), and advanced glycation end products (AGEs) along with the reduction of the activity of glyoxalase-I (GLO-I) contribute to the alteration of protein structure and function, oxidative stress, and expression of proinflammatory cytokines and growth factors as tumor necrosis factor-α (TNF-α) and transforming growth factor-1β (TGF-1β). Cooperatively, these changes result in glomerular hyperfiltration, glomerular hypertension, renal hypertrophy, and altered glomerular composition, ultimately cause interstitial fibrosis and glomerulosclerosis which is manifested clinically as albuminuria and hypertension [3].
AGE inhibitors and the inducers of GLO-1 can play a beneficial role in the prevention or delaying diabetes complications. On the other hand, natural ingredients have anti-glycation, antioxidant and anti-inflammatory properties and could improve diabetes complications [4–7]. 1,8 cineole (Cin) or eucalyptol a monoterpene naturally found in essential oils of various plant species, has been widely reported for the bioactivities. More over, It possesses diverse pharmacological activities including anti-microbial, anticancer, anti-inflammatory, antioxidation [8]. There are few studies about the renoprotective property of Cin in db/db mice and there are no studies about its effect on diverse glycation products and the activity of GLO-I in diabetes. Therefore, in this study, the effect of Cin on glycation, oxidative stress, and inflammatory markers, as well as the activity of GLO-I and renal histopathological alterations in the type 2 diabetes model of rats, has been investigated.
Materials and methods
Materials
Cineole, CaCl2, NaCl and EDTA from Merck Chemical Co. Streptozotocin (STZ), MGO, nitro blue tetrazolium (NBT), oxalic acid, 5-hydroxymethylfurfuraldehyde, and Triton X-100, were purchased from Sigma Chemical Co. The 0.45 μm syringe filters were obtained from Millipore purchased from Sigma or Merck Chemical Companies.
In vivo studies
Animal model of type 2 diabetes
In this study, with the approval of the ethics committee at Ardabil University of Medical Sciences with the code of Ethics IR.ARUMS.REC.1397.176 and by the principles of the standard of working with laboratory animals. Male Wistar rats, 8 weeks old and weighing 200 ± 15, were purchased from the Pasteur Institute of Iran, Karaj. Animals maintained under controlled conditions. After two weeks, they were divided into four groups, including a normal group, a diabetic group, and two similar groups under Cin treatment (200 mg/kg). After 12 h fasting, type 2 diabetes was induced in rats with a single intraperitoneally (i.p.) injection of nicotinamide (210 mg/kg body weight in the Na-citrate buffer, pH 4.5) and streptozotocin (55 mg/kg body weight in the citrate buffer, 15 min later) [9]. After three days, animals with fasting blood sugar (FBS) > 11 mmol/L, was accepted as a diabetic rats. The dose of Cin was selected based on the best activities of antioxidant and anti-inflammatory of it in the cited dose [10] and our pilot study.
The blood samples of each animal were taken from hurt at the end of the study and were.
allowed to clot at room temperature. The serum was separated by centrifugation at 5000 rpm for 15 min and was stored at − 70 °C for measurements. Their kidneys were dissected and weighted instantly.
Determination of biochemical parameters
Fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), LDL, and HDL as well as serum creatinine (Cr) and protein excretion in urine (PU) were measured by photometric methods. Besides, the atherogenic index was computed with LDL/HDL ratio. The sera insulin levels were assayed with the enzyme-linked immunosorbent assay (ELISA) rat kit (Mercodia, Uppsala, Sweden) and HOMA-IR (homeostasis model assessment of insulin resistance) as an index of insulin resistance and beta-cell function [11] was calculated as explained before [12].
Determination of glycated protein products
Glycated albumin (g-Alb) was measured by a photometric method based on NBT chloride reduction [13, 14]. Methylglyoxal (MGO) was assayed by a reverse phase HPLC [14, 15]. The fluorescent AGEs were determined in the serum of rats as we explained previously [12, 16].
Determination of oxidative stress and inflammatory markers
Advanced oxidation protein products (AOPP) were measured based on the spectrophotometric method using chloramine-T as a standard [17]. Commercial assay kits (Cayman Chemical Co., Ann Arbor, MI) were used for measuring of malondialdehyde (MDA) and reduced glutathione (GSH) levels. Tumor necrosis factor-α (TNF-α), TGF-β1 in serum were determined using ELISA kits (Immunotech, France).
Histological assessment
Glomerular volume/kidney
The kidneys were fixed in formal saline solution and routinely were processed. Periodic acid-Schiff (PAS) was used for staining of random sections (5 μm thick) of the renal cortex. The motic image plus (version 2) software program on PAS stained tissue sections at 400 × magnification through a motic microscope equipped with a motic camera was used for the determination of The surface areas of 100 glomeruli. The mean glomerular volume (VG) was computed with the method of Weibel and Gomez. VG = Area 1.5 × 1.38/1.01 where 1.38 and 1.01 respectively show the shape coefficient and the size distribution coefficient [18].
Glomerulosclerosis assessment
The severity of glomerulosclerosis was investigated semiquantitatively. Severity in tissue sections was assessed by assigning a score 1–4 to each glomerulus according to the tuft demonstrating sclerosis: normal glomeruli = 0; up to 25% involvement = 1; 25–50% involvement = 2; 50–75% involvement = 3 and more than 75% involvement = 4. The glomeruli appeared randomly in microscopic fields, were selected for the assessment. At least 150 glomeruli were assessed in kidney sections of each group of animals.
Leukocyte infiltration assessment
The glomeruli were chosen for the valuation that appeared randomly at 400 time magnification in microscopic fields. Severity in infiltration was evaluated by assigning a score 1–4 to each glomerulus by the tuft demonstrating leukocyte infiltration: normal = 0; up to 25% complication = 1; 25–50% complication = 2; 50–75% complication = 3 and more than 75% complication = 4 [19].
Statistical analysis
All data were expressed as mean ± S.D (standard deviations). Different variables in all four groups were compared with multiple analysis of variance (MANOVA-TUKEY) test by using SPSS version 16 statistical. Besides, significance was defined as p < 0.05.
Results
Glomerular volume and glomerular number (Table 1) respectively elevated and increased critically in the untreated diabetic rats in comparison with the normal group (P < 0.05). Even so, There was no difference in the cited parameters between the treated diabetic group and the normal group.
Table 1.
The effect of cineole on glomerular volume, glomerular number and glomerulosclerosis, creatinine, and proteinuria the normal (N) and diabetic rats (D)
| Parameter | Groups | |||
|---|---|---|---|---|
| N | N (Cineole) | D | D (Cineole) | |
| Glomerular volume/kidney (mm3) | 25.76 ± 1.06 | 23.96 ± 1.01 | 62.85 ± 2.41 N | 36.27 ± 2.62 N, D |
| Glomerular number/kidney | 27998.76 ± 1669.24 | 28092.62 ± 1695.76 | 20994.63 ± 1008.13 N | 27782.33 ± 1245.87D |
| Glomerular sclerosis (Score 0–4) | 0.21 ± 0.13 | 0.19. ± 0.11 | 1.97 ± 0.19 N | 0.89.53 ± 0.49 N, D |
| Leukocyte infiltration (Score 0–4) | 0.13 ± 0.05 | 0.12. ± 0.04 | 1.84 ± 0.17 N | 0.78 ± 0.08 N, D |
| Creatinine (µmol/l) | 58.32 ± 3.31 | 54.61 ± 2.96 | 92.41 ± 5.09 N | 78.06 ± 3.68 N, D |
| Proteinuria (mg/24 h) | 28.94 ± 1.69 | 24.62 ± 1.53 | 271.83 ± 13.02 N | 122.31 ± 7.92 N, D |
N Indicates significance of data comparing normal group (N) with other groups (P < 0.05)
D Indicates significance of data comparing diabetic-atherosclerotic group (D) with other groups (P < 0.05)
Glomerulosclerosis, leukocyte infiltration (Fig. 1A, B, and C), Cre, and PU (Table 1) were significantly were lower in the treated group than the untreated diabetic group. Although, the treatment could not significantly maintain the cited parameters at the same levels as the normal group (p < 0.05).
Fig.1.
Effect of 1,8 cineole (Cin) on renal histopathological parameters in the photomicrographsof renal sections with periodic acid shiff (PAS). (A) Micrograph (400 ×) from the kidney of a rat in the normal group: without glumerosclerosis and lymphocyste infiltration. (B) Micrograph (400 ×) from the kidney of a rat in the diabetic group: glumerosclerosis (Score 3) and lymphocyste infiltration. (C) Micrograph (400 ×) from the kidney of a rat in the treated diabetic group with 1,8 cineole: glumerosclerosis (Score 1) and low level of lymphocyste infiltration
The levels of FBS, HOMA-IR TG, TC, and atherogenic index increased but insulin level decreased in the diabetic group (Table 2). Furthermore, Cin significantly corrected hyperglycemia, insulin resistance, and dyslipidemia in the diabetic group (p < 0.001).
Table 2.
The effect of cineole on fasting blood sugar, insulin, HOMA-IR, and lipid in the normal (N) and diabetic rats (D)
| Parameter | Groups | |||
|---|---|---|---|---|
| N | N (Cineole) | D | D (Cineole) | |
| Fasting blood sugar (mmol/L) | 4.49 ± 0.36 | 4.87 ± 0.32 | 16.27 ± 0.84 N | 9.01 ± 0.65 N, D |
| Insulin (µU/mL) | 18.07 ± 1.22 | 17.46 ± 0.95 | 8.36 ± 0.54 N | 11.13 ± 0.69 N, D |
| HOMA-IR | 3.60 ± 0.19 | 3.77 ± 0.21 | 6.67 ± 0.37 N | 4.45 ± 0.24 N, D |
| Triglyceride (mmol/l) | 0.87 ± 0.06 | 0.82 ± 0.05 | 2.65 ± 0.13 N | 1.39 ± 0.71 N, D |
| Total cholesterol (mmol/l) | 1.94 ± 0.12 | 1.82 ± 0.10 | 4.27 ± 0.26 | 3.18. ± 0.19 N, D |
| HDL (mmol/l) | 1.34 ± 0.06 | 1.41 ± 0.07 | 0.38 ± 0.02 N | 0.79 ± 0.04 N, D |
| LDL (mmol/l) | 0.43 ± 0.03 | 0.38 ± 0.02 | 2.27 ± 0.12 N | 1.36 ± 0.06 N, D |
| LDL/HDL | 0.34 ± 0.01 | 0.29 ± 0.01 | 9.97 ± 0.21 N | 3.67 ± 0.11 N, D |
N Indicates significance of data comparing normal group (N) with other groups (P < 0.001)
D Indicates significance of data comparing diabetic-atherosclerotic group (D) with other groups (P < 0.001)
Induction of diabetes in the rats elevated early to end products of glycation (g-Alb, MGO, and AGEs), oxidative stress (AOPP, MDA, and GSH), and inflammatory (TNF-α and TGF-1β) markers as well as decreased the level of GSH and the activity of GLO-I (Table 3) but the treatment recompensated the cited changes in the diabetic rats (p < 0001).
Table 3.
The effect of cineole on glycation, oxidative stress and inflammatory markers as well as activity of glyoxalase-I in the normal (N) and diabetic rats (D)
| Parameter | Groups | |||
|---|---|---|---|---|
| N | N (Cineole) | D | D (Cineole) | |
| Glycated albumin (μmol/l) | 149.92 ± 8.86 | 145.63 ± 9.65 | 26735 ± 1623 N | 27.61 ± 12.52 N, D |
| Methylglyoxal (μmol/l) | 21.80 ± 1.43 | 19.86 ± 1.12 | 65.29 ± 3.907 N | 41.64 ± 266 N, D |
| Advanced glycation end products (μmol/l) | 43.92 ± 3.24 | 39.67 ± 2.96 | 97.01 ± 5.93 N | 71.53 ± 4.05 N, D |
| Advanced oxidation protein products (μmol/l) | 43.92 ± 3.24 | 39.67 ± 2.96 | 97.01 ± 5.93 N | 71.53 ± 4.05 N, D |
| Malondialdehyde (μmol/l) | 11.64 ± 0.66 | 10.93 ± 0.58 | 88.94 ± 6.31 N | 59.46 ± 3.28 N, D |
| Glutathione (μmol/l) | 205.37 ± 12.26 | 198.58 ± 11.53 | 83.04 ± 4.93 N | 124.92 ± 6.89 N, D |
| Tumor necrosis factor-α (pg/ml) | 147.62 ± 9.31 | 139.94 ± 8.96 N | 297.88 ± 17.54 N | 226.39 ± 15.26 N, D |
| Transforming growth factor-1β | 32.76 ± 3.04 | 28.87 ± 2.05 N | 73.29 ± 3.64 N | 49.82 ± 2.96 N, D |
| Glyoxalase-I (U/ml) (pg/ml) | 40.84 ± 3.21 | 42.51 ± 3.06 N | 19.93 ± 2.23 N | 28.87 ± 2.97 N, D |
N Indicates significance of data comparing normal group (N) with other groups (P < 0.001)
D Indicates significance of data comparing diabetic-atherosclerotic group (D) with other groups (P < 0.001)
Discussion
In this study, 1,8 cineole improved renal dysfunction in diabetic rats via the reduction of various glycation, oxidative stress, and inflammatory markers. Moreover, the treatment showed a beneficial effect on glucose and lipid metabolism as well as the activity of glyoxalase-I.
Induction of diabetes in the rat due to glomerulosclerosis (Fig. 1A, B, and C), lymphocyte infiltration, glomerular hypertrophy, and the reduction of glomerular number leads to the elevation of urinary protein excretion and serum creatinine (Table 1). Cin diminished the levels of kidney dysfunction markers in diabetic rats (p < 0.001). The protective effect of the treatment on kidney tissue confirms via the lowering effect of it on the level of TGF-1β (Table 3) as an inflammatory cytokine as a major cause of DN (p < 0.001). Lately, the ameliorative effect of Cin [20] on kidney dysfunction respectively in the diabetic-nephropathy rat model and db/db mice due to the reduction of TGF-β1 has been reported. Moreover, the inhibitory effect of Cin on barrier dysfunction of podocytes and following proteinuria in db/db mice has been represented [8].
Glycemia motivates more damage to the tissues like kidneys that are an insulin-independent organ, and the flow of glucose into the cells is directed through the circulating glucose levels and the expression of facilitative glucose transporters [21]. Moreover, glycemia induces the raising g-Alb, MGO, and AGEs levels that interposed generation TNF-α and IL-6 may directly impede insulin signaling [22] and involve in DN [12]. Probably hyperglycemia interfered in tubular epithelial cell–cell adhesion and induced expansion and deposition of matrix-producing renal cells. Cin lowered the levels of blood glucose and insulin resistance index or HOMA (Table 1) in the diabetic rats (p < 0.001). The hypoglycemic effect of Cin may be through an improving effect on the pancreatic β-cells activity, which is consistent with the antioxidant and anti-glycation, anti-inflammatory properties of it. Recently, the lowering effect of Cin on blood glucose in db/db mice has been reported [20].
Renal disorder, oxidative stress, inflammation, and insulin resistance are following the elevation of glycation products as g-Alb, MGO, and AGEs along with a reduction of the activity of glyoxalase-1 in chronic kidney disease [12, 14]. The treatment displayed anti-glycating activity with the induction activity of Glo-1 diabetic rats and the reduction of diverse glycated products (Table 2) in the diabetic rats (P < 0.001). Based on our literature review, the effect of Cin on the generation of different glycation products and Glo system activity in diabetes has not been reported. Cin may reduce diverse glycation products with antioxidant and scavenger properties as well as activation of Glo-I [12].
Presumably, oxidative stress has a central role in the pathophysiology of diabetic nephropathy. Cin decreased AOPP as markers of oxidative damage to proteins and inflammation and MDA as a marker of lipid peroxidation in the diabetic rats. Further, the higher level of GSH level in diabetic rats validated the potent antioxidant activity of the treatment (Table 2). The reducing effect of the treatment on oxidative stress in cigarette smoke-induced acute lung inflammation in mice via the reduction of has been shown [23].
Pro-inflammatory cytokines contribute to renal lesions through cellular injury, change in the glomerular protein permeability barrier and, promotion of intracranial inflammatory damage that causes diabetic nephropathy [24]. The levels of the inflammatory marker, TNF-α, and TGF-1β in the serum of the diabetic rat elevated but Cin compensated these changes (Table 2) and showed the potent anti-inflammatory effect (P < 0.001). The anti-inflammatory property of the treatment in cigarette smoke-induced acute lung inflammation in mice due to its activity to decrease NF-kappa B p65 subunit activation, following in diminished inflammatory cells and reduced secretion of cytokines as TNF-α has been reported [23].
Dyslipidemia is a major aspect and risk factor of diabetic nephropathy [25] that contribute to the initiation and development of diabetic nephropathy due to the raising inflammatory pathways that follow the production of reactive oxygen species (ROS) [26]. The treatment (Table 2) corrected dyslipidemia in diabetic rats (p < 0.001). The lipid lowering effect of Cin in the atherosclerosis model of zebrafish has been presented [27].
Conclusions
1,8 cineole ameliorated diabetic nephropathy via the reduction of TGF-1β following to decrease the formation of different glycation products, oxidative stress, and inflammatory process with the induction of the activity of glyoxalase-I and the advantageous effect on glucose and lipid metabolism as well as insulin sensitivity in type 2 diabetic rats.
Acknowledgements
The authors are thankful to Ardabil University of medical sciences for financial support
Authors contribution
1) Authors make substantial contributions to conception and design, and/or acquisition of data, and/or analysis and interpretation of data: Mahdavifard S & Nakhjavani M
2) Authors participate in drafting the article or revising it critically for important intellectual content: Mahdavifard S & Nakhjavani M
3) Author gives final approval of the version to be submitted and any revised version: Mahdavifard S
The study to be submitted, that it is an original study presenting novel work, that it has not been previously submitted to or accepted by any other journal, that is has been approved by all authors, that ethics approval and written informed consent have been obtained, and explain whether any author has a conflict of interest.
Funding
Ardabil University of medical sciences.
Declarations
Conflict interest
We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.
Footnotes
Publisher's note
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References
- 1.Xiong Y, Zhou L. The signaling of cellular senescence in diabetic nephropathy. Oxid Med Cell Longev. 2019;2019:7495629–7495645. doi: 10.1155/2019/7495629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Neelofar K, Ahmad J. Amadori albumin in diabetic nephropathy. Indian J Endocrinol Metab. 2015;19(1):39–46. doi: 10.4103/2230-8210.146863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Rabbani N, Thornalley PJ. The critical role of methylglyoxal and glyoxalase 1 in diabetic nephropathy. Diabetes. 2014;63(1):50–52. doi: 10.2337/db13-1606. [DOI] [PubMed] [Google Scholar]
- 4.Mahdavifard S, Nakhjavani M. Effect of pyridoxal phosphate on atherosclerosis and nephropathy progression in atherosclerotic rats. J Adv Med Biomed Res. 2021;29(132):21–27. doi: 10.30699/jambs.29.132.21. [DOI] [Google Scholar]
- 5.Mahdavifard S, Nakhjavani M. Preventive effect of eucalyptol on the formation of aorta lesions in the diabetic-atherosclerotic rat. IJPM. 2021;12(1):45–50. doi: 10.4103/ijpvm.IJPVM_319_19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Mahdavifard S, Dehghani R, Jeddi F, Najafzadeh N. Thiamine reduced metabolic syndrome symptoms in rats via down-regulation of hepatic nuclear factor-kβ and induction activity of glyoxalase-I. Iran J Basic Med Sci. 2021;24:46–53. doi: 10.22038/ijbms.2021.53707.12086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Mahdavifard S, Nakhjavani M. Thiamine pyrophosphate improved vascular complications of diabetes in rats with type 2 diabetes by reducing glycation, oxidative stress, and inflammation markers. Med J Islam Repub Iran. 2020;34(1):331–336. doi: 10.34171/mjiri.34.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Linghu K-G, Wu G-P, Fu L-Y, Yang H, Li H-Z, Chen Y, Yu H, Tao L, Shen X-C. 1,8-Cineole ameliorates LPS-induced vascular endothelium dysfunction in mice via PPAR-gamma dependent regulation of NF-kappaB. Front Pharmacol. 2019;10:178–189. doi: 10.3389/fphar.2019.00178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Taha H, Arya A, Paydar M, Looi CY, Wong WF, Vasudeva Murthy CR, Noordin MI, Mohd Ali H, Mustafa AM, Hadi AHA. Upregulation of insulin secretion and downregulation of pro-inflammatory cytokines, oxidative stress and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats by Pseuduvaria monticola bark extract. Food Chem Toxicol. 2014;66:295–306. doi: 10.1016/j.fct.2014.01.054. [DOI] [PubMed] [Google Scholar]
- 10.Lima PR, et al. 1,8-cineole (eucalyptol) ameliorates cerulein-induced acute pancreatitis via modulation of cytokines, oxidative stress and NF-κB activity in mice. Life Sci. 2013;92(24–26):1195–1201. doi: 10.1016/j.lfs.2013.05.009. [DOI] [PubMed] [Google Scholar]
- 11.Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. omeostasis model assessment: insulin resistance and B cell function from fasting plasma glucose and insulin concentrations in man. Diabetologi. 1985;28(412):419. doi: 10.1007/BF00280883. [DOI] [PubMed] [Google Scholar]
- 12.Mahdavifard SB, Bathaie SZ, Nakhjavani M, Taghikhani M. The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat. Eur J Med Chem. 2016;121:892–902. doi: 10.1016/j.ejmech.2015.11.035. [DOI] [PubMed] [Google Scholar]
- 13.Xu Y-J, Wu X-Q, Liu W, Lin X-H, Chen J-W, He R-q. A convenient assay of glycoserum by nitroblue tetrazolium with iodoacetamide. Clin Chim Acta. 2002;325(1-2):127–131. doi: 10.1016/S0009-8981(02)00277-2. [DOI] [PubMed] [Google Scholar]
- 14.Mahdavifard SB. SZ Nakhjavani, M Heidarzadeh, H, L-cysteine is a potent inhibitor of protein glycation on both albumin and LDL, and prevents the diabetic complications in diabetic–atherosclerotic rat. Food Res Int. 2014;62:909–916. doi: 10.1016/j.foodres.2014.05.008. [DOI] [Google Scholar]
- 15.Deng Y, Peter HY. Simultaneous determination of formaldehyde and methylglyoxal in urine: involvement of semicarbazide-sensitive amine oxidase-mediated deamination in diabetic complications. J Chromatogr Sci. 1999;37(9):317–322. doi: 10.1093/chromsci/37.9.317. [DOI] [PubMed] [Google Scholar]
- 16.Kalousova M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res. 2002;51(6):597–604. [PubMed] [Google Scholar]
- 17.Witko-Sarsat V, Nguyen-Khoa T, Jungers P, Drüeke TB, Descamps-Latscha B. Advanced oxidation protein products as a novel molecular basis of oxidative stress in uraemia. Nephrol Dial Transplant. 1999;14(suppl 1):76–78. doi: 10.1093/ndt/14.suppl_1.76. [DOI] [PubMed] [Google Scholar]
- 18.Zoja C, Perico N, Bergamelli A, Pasini M, Morigi M, Dadan J, Belloni A, Bertani T, Remuzzi G. Ticlopidine prevents renal disease progression in rats with reduced renal mass. Kidney Int. 1990;37(934):942. doi: 10.1038/ki.1990.68. [DOI] [PubMed] [Google Scholar]
- 19.Weidner S, Carl M, Riess R, Rupprecht HD. Histologic analysis of renal leukocyte infiltration in antineutrophil cytoplasmic antibody-associated vasculitis: importance of monocyte and neutrophil infiltration in tissue damage. Arthritis Rheum. 2004;50(11):3651–3657. doi: 10.1002/art.20607. [DOI] [PubMed] [Google Scholar]
- 20.Kim DY, Kang M-K, Park S-H, Lee E-J, Kim Y-H, Oh H, Choi Y-J, Kang Y-H. Eucalyptol ameliorates Snail1/β-catenin-dependent diabetic disjunction of renal tubular epithelial cells and tubulointerstitial fibrosis. Oncotarget. 2017;8(63):106190–106205. doi: 10.18632/oncotarget.22311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Gnudi L, Thomas SM, Viberti G. Mechanical forces in diabetic kidney disease: a trigger for impaired glucose metabolism. J Am Soc Nephrol. 2007;18(8):2226–2232. doi: 10.1681/ASN.2006121362. [DOI] [PubMed] [Google Scholar]
- 22.Song F, Schmidt AM. Glycation and insulin resistance novel mechanisms and unique targets? Arterioscler Thromb Vasc Biol. 2012;32(8):1760–1765. doi: 10.1161/ATVBAHA.111.241877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Kennedy-Feitosa E, Porto LC, Schmidt M, Okuro R, Zin WA, Brito-Gitirana L, Valenca SS. Eucalyptol attenuates cigarette smoke-induced acute lung inflammation and oxidative stress in the mouse. Pulm Pharm Ther. 2016;41(11):18. doi: 10.1016/j.pupt.2016.09.004. [DOI] [PubMed] [Google Scholar]
- 24.Aratani Y. Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys. 2018;640:47–52. doi: 10.1016/j.abb.2018.01.004. [DOI] [PubMed] [Google Scholar]
- 25.Barter PJ. Lipoprotein metabolism and CKD: overview. Clin Exp Nephrol. 2014;18:243–246. doi: 10.1007/s10157-013-0866-9. [DOI] [PubMed] [Google Scholar]
- 26.Toyama T, Shimizu M, Furuichi K, Kaneko S, Wada T. Treatment and impact of dyslipidemia in diabetic nephropathy. Clin Exp Nephrol. 2014;18(201):5. doi: 10.1007/s10157-013-0898-1. [DOI] [PubMed] [Google Scholar]
- 27.Cho KH. 1,8-cineole protected human lipoproteins from modification by oxidation and glycation and exhibited serum lipid-lowering and anti-inflammatory activity in zebrafish. BMB Rep. 2012;45(10):565–570. doi: 10.5483/BMBRep.2012.45.10.044. [DOI] [PubMed] [Google Scholar]