Received 2018-05-22

Revised 2018-07-06

Accepted 2018-08-07

Preventive Effect of Different Wild Pistachio Oils on Oxidative Stress Markers, Liver Enzymes, and Histopathological Findings in a Metabolic

Syndrome Model

Sanaz Jamshidi1, Najmeh Hejazi2, Mohammad-Taghi Golmakani3, Nader Tanideh4, Mina Heidari Esfahani5

1 Department of Clinical Nutrition, School of Nutrition and food sciences, Shiraz University of Medical Sciences, Shiraz, Iran

2 Nutrition research center, Department of Clinical Nutrition, School of Nutrition and food sciences, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz, Iran

4 Stem Cell and Transgenic Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

5 Pathology Department, Birjand University of Medical Sciences, Birjand, Iran

Abstract

Background: Wild pistachio (Pistacia Atlantica mutica) species with wide distribution in Iran have different nutrition properties and may have therapeutic effects in metabolic syndrome. Metabolic syndrome, as a prevalent health problem, is a main risk factor for different chronic diseases such as diabetes, fatty liver and cardiovascular diseases. The present study aimed to evaluate the preventive effects of mixture, kernel, and hull oil of wild pistachio (WP) on oxidative stress markers, liver function and histopathological findings in metabolic syndrome induced rats. Materials and Methods: After oil extraction by cold press method and chemical analysis, rats were divided into 6 groups. Group 1 received normal saline; group 2 received 2cc fructose solution and 0.5cc normal saline; and groups 3, 4, 5 and 6 received 2 cc fructose solution and 0.5 cc sunflower oil, mixture, hull and kernel oils of WP for 10 weeks, respectively. Then, glycemic indices, oxidative stress, liver enzymes and histopathological examination were determined using standard laboratory tests. Results: WP Kernel and mixture oils notably decreased the fasting blood sugar and insulin resistance compared with the fructose group. Insulin level was significantly increased in the kernel oil group (P<0.05). There was no significant difference in oxidative stress, liver enzymes and histopathology parameters among the groups. Conclusion: Kernel oil of WP improved hyperglycemia, insulin resistance and insulin secretion, but the changes in oxidative stress markers, liver enzymes and histopathologic results were not significant among the groups. [GMJ.2019;8:e1238] DOI:10.22086/gmj.v8i0.1238

Keywords: Wild Pistacia; Oils; Liver Function Tests; Insulin Resistance

Correspondence to:

Assistant professor, Nutrition research center, Department of Clinical Nutrition, School of Nutrition and food sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Telephone Number: +989177020859

Email Address: najmehhejazi@gmail.com

GMJ.2019;8:e1238

www.gmj.ir

Introduction

Metabolic syndrome is a combination of metabolic disturbances and is also known as the insulin resistance (IR) syndrome [1, 2]. Atherogenic dyslipidemia, elevated blood pressure, hyperglycemia, and prothrombotic and proinflammatory states are the disorders related to metabolic syndrome, which can increase mortality from cardiovascular diseases [3-5]. IR is an underlying factor of metabolic syndrome, and investigators believe that it can directly cause other metabolic abnormalities [5]. On the other hand, oxidative stress may have destructive effects on individuals with metabolic syndrome [6]. Till date, there are no clear therapeutic approaches for metabolic syndrome; however, it seems that dietary interventions can play an important role in its improvement [7]. Modifiable lifestyle factors such as intake of vegetables and fruits, low-glycemic-index foods, low salt, antioxidants, and dietary fat intake and its quality can improve the metabolic profile [6, 8, 9]. Total fat intake is associated with IR and risk of metabolic syndrome. As the replacement of saturated fatty acids with monounsaturated fatty acids (MUFA) can improve the IR and risk of metabolic syndrome, introducing local sources of MUFA may have preventive effects [10]. Pistacia atlantica var. mutica, which is called baneh in local areas of Iran, is a wild pistachio (WP) from Anacardiaceae family and grows in the western, central, and eastern parts of the country. It is composed of a kernel, hull, and wooden shell [11-13]. Different parts of this plant have been used traditionally. Local residents use the fruit of the plant as a nut and its resin as a gum, mouth freshener, and treatment for gastrointestinal ulcers and skin burn wound [14-16]. Furthermore, a study showed that the antimicrobial activity of its leaves is due to its high content of phenolic compounds [17]. On the basis of previous studies, oil of WP fruit is considered a major source of oleic acid, the most abundant MUFA, and some valuable lipid-soluble bioactive compounds such as tocopherols, phenols, and phytosterols [13, 18].Therefore, the aim of this study was to investigate the preventive effects of different WP oils on oxidative stress status, liver enzymes, and histopathological findings in metabolic syndrome models.

Materials and Methods

Oil Preparation

Fresh fruits of WP were collected from Nurabad (Zagros forest), Fars province, Iran, in October 2016. The confirmation of the species with voucher specimen (no. 2817) was approved by an expert in the Traditional Pharmacy Department, Shiraz University of Medical Sciences, Shiraz, Iran. Different parts of the fruit (the green hull and the kernel) were separated and after drying in the shade, oil extraction was conducted using the cold press method (cold press device: calibre35 mm, Iran). The oils were filtered and centrifuged at 4000 revolutions per min for 15 min, and then, we stored the hull, kernel, and mixture oils (40 percent kernel and 60 percent hull oils) with minimum exposure to oxygen in dark bottles in the refrigerator. According to a study [19], the effective dose of olive oil was 1.3 and 1.7 mL/kg, and as the MUFA content of olive oil is about 64% and the MUFA content of WP is about 52%, the dosage used in this study was 2.2 mL/kg/day, with a coefficient of 1.27.

Chemical Profile of the Oils

The sterol content and fatty acid composition were analyzed by a gas chromatograph machine, using a Beifen system (3420A, China). The National Iranian Standard Nos. ISIRI 9670 and ISIRI 6081 were used to calculate the sterol content. The amount of total phenols was measured using the Folin-Ciocalteu reagent at 725 nm. Results were expressed as mg of gallic acid per g of oil. The reversed-phase high-performance liquid chromatography column VIT F (Knauer Smart Line, Germany) and UV detection at 295 nm were used for the structural elucidation of tocopherol. The total tocopherol content was estimated by comparing it with standards purchased from Sigma. In addition, the International Dairy Federation spectrophotometric method was used for peroxide value determination.

Animals

In this study, we used 72 male Sprague-Dawley rats having a mean age of 6 to 8 weeks and weight of 170 to 220 g each, purchased from the center of experimental and comparative medicine, Shiraz University of Medical Sciences, Shiraz. Animals were housed in standard conditions (temperature: 22±2.c, humidity: %50±5 and lighting: 12 hours light/dark cycles). They had access to ad libitum drinking water and were fed a chow diet (Pars Dam Co., Tehran, IRAN). Our study protocol was approved by the ethics committee of Shiraz University of Medical Sciences (registration number: 95-01-84-12937) and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Induction of Metabolic Syndrome

We induced metabolic syndrome in the rats by administering 8 g/kg body weight per day of fructose (Merch Co., Germany) by gavaging fructose solution (as 50/50 with water) [20].

Experimental Design

The experimental groups were selected as follows:

Table 1. Chemical Composition of WP Kernel Oil, WP Hull Oil and Sunflower Oil

Parameters

WP kernel oil

WP hull oil

Sunflower oil

Fatty acids (percent)

16:0

10.03

23.74

7.39

18:1

51.17

54.33

25

18:2

32.85

5.84

63.2

Others

5.32

15.39

4.21

Sterols

B-sitosterol (percent)

84

82.44

61.11

Total (mg/kg)

3811.12

1569.47

2700

Total tocopherol (mg/kg)

350.15

1070.49

582

Total phenol (mg/kg)

4.25

89.5

1.2

Peroxide value (mequiv O2/kg oil)

0.8

4.2

0.7

Table 2. Glycemic Indices, Liver Enzymes and Oxidative Stress Parameters of Each Group Fed with Different Oils

Variables

Control (mean±SD)

fructose

(mean±SD)

Sunflower oil

+fructose

(mean±SD)

WP mixture oil

+fructose

(mean±SD)

WP hull oil

+fructose

(mean±SD)

WP kernel oil

+fructose

(mean±SD)

P-value

FBS

(mg/dl)

114.45±28.42

178.00±17.32a

174.72±38.38a

120.45±14.09bc

150.30±27.60a

123.45±24.88bc

<.001

Insulin

(µIU/ml)

1.90±0.24

1.59±0.17a

1.47±0.18a

1.78±0.18c

1.63±0.22a

1.85±0.18bc

<.001

HOMA-IR

0.53±0.13

0.7±0.12a

0.64±0.19

0.53±0.10b

0.60±0.13

0.56±0.11b

0.04

AST** (U/L)

13(2-107)

2.5(2-79.25)

125(75-146)

2(2-30)

36(2.75-119.25)

65(6-122)

0.11

ALT (U/L)

71.18±14.98

63.70±9.38

64.27±13.40

67.54±12.17

59.20±18.65

60.36±14.50

0.38

MDA**

(pg/ml)

3.92(3.58-5.25)

4.27(3.75-5.78)

3.83(3.7-4.92)

3.92(3.87-4.85)

4.00(3.76-4.20)

4.08(3.50-4.37)

0.86

SOD

(u/ml)

30.30±1.49

31.82±1.04

32.24±2.81

32.45±1.19

32.29±1.62

31.65±2.44

.11

*P<0.05 considered significant

a significant difference compared to the control group

B significant difference compared to the fructose group

Csignificant difference compared to the sunflower oil group

D significant difference compared to the kernel oil group

** non-parametric data express as median (IQR) (25th percentile and 75th percentile)

FBS: Fasting blood sugar; HOMA-IR: Homeostatic model assessment of insulin resistance; AST: Aspartate aminotransferase; ALT: Alanine transaminase; MDA: Malondialdehyde; SOD: Superoxide dismutase

Table 3. Total Score of Histopathological Findings Based on Central Venous Congestion, Congestion and Dilation of the Hepatic Sinusoids and Inflammation of the Portal Tracts

Control

(mean±SE)

Fructose

(mean±SE)

Sunflower oil

(mean±SE)

Mixture oil

(mean±SE)

Hull oil

(mean±SE)

Kernel oil

(mean±SE)

P-value

Total score of histopathological findings*

0.09±0.09

0.8±0.44

1.00±0.26

0.45±0.15

0.3±0.15

0.18±0.12

0.06

*Mean ± Standard error

Figure 1. Histopathologic results of rat liver in the 6 groups. A: Histology of normal rat liver in control group. B and C: Histology of rat liver in fructose and sunflower oil groups with vascular congestion and lymphocytic inflammation. D, E and F: Histology of normal rat liver in WP mixture, hull and kernel oil groups (original magnification ×40)

References

  1. DeFronzo RA, Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes care. 1991;14(3):173-94.
  2. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365(9468):1415-28.
  3. Trevisan M, Liu J, Bahsas FB, Menotti A, Factor R, Group LER. Syndrome X and mortality: a population-based study. Am J Epidemiol. 1998;148(10):958-66.
  4. Zimmet P, Magliano D, Matsuzawa Y, Alberti G, Shaw J. The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb. 2005;12(6):295-300.
  5. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome. Circulation. 2004;109(3):433-8.
  6. Ford ES, Mokdad AH, Giles WH, Brown DW. The metabolic syndrome and antioxidant concentrations. Diabetes. 2003;52(9):2346-52.
  7. Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC. Dietary patterns, insulin resistance, and prevalence of the metabolic syndrome in women. Am J Clin Nutr. 2007;85(3):910-8.
  8. Riccardi G, Rivellese A. Dietary treatment of the metabolic syndrome—the optimal diet. Br J Nutr. 2000;83(S1):S143-S8.
  9. Freire RD, Cardoso MA, Gimeno SG, Ferreira SR. Dietary fat is associated with metabolic syndrome in Japanese Brazilians. Diabetes care. 2005;28(7):1779-85.
  10. Tierney AC, McMonagle J, Shaw D, Gulseth H, Helal O, Saris W, et al. Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome—LIPGENE: a European randomized dietary intervention study. Int J Obes (Lond). 2011;35(6):800-9.
  11. Pourreza M, Shaw JD, Zangeneh H. Sustainability of wild pistachio (Pistacia atlantica Desf.) in Zagros forests, Iran. For Ecol Manage. 2008;255(11):3667-71.
  12. Farhoosh R, Tavakoli J, Khodaparast MHH. Chemical composition and oxidative stability of kernel oils from two current subspecies of Pistacia atlantica in Iran. J Am Oil Chem Soc. 2008;85(8):723.
  13. Farhoosh R, Khodaparast MHH, Sharif A. Bene hull oil as a highly stable and antioxidative vegetable oil. Eur J Lipid Sci Technol. 2009;111(12):1259-65.
  14. Delazar A, Reid R, Sarker S. GC-MS analysis of the essential oil from the oleoresin of Pistacia atlantica var. mutica. Chem Nat Compd. 2004;40(1):24-7.
  15. Haghdoost F, Baradaran Mahdavi MM, Zandifar A, Sanei MH, Zolfaghari B, Javanmard SH. Pistacia atlantica resin has a dose-dependent effect on angiogenesis and skin burn wound healing in rat. Evid Based Complement Alternat Med. 2013;13(6):1-8.
  16. Bozorgi M, Memariani Z, Mobli M, Salehi Surmaghi MH, Shams-Ardekani MR, Rahimi R. Five Pistacia species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): a review of their traditional uses, phytochemistry, and pharmacology. ScientificWorldJournal. 2013;15(3):1–33.
  17. Benhammou N, Bekkara FA, Panovska TK. Antioxidant and antimicrobial activities of the Pistacia lentiscus and Pistacia atlantica extracts. Afr J Pharm Pharmacol. 2008;2(2):022-8.
  18. Saber-Tehrani M, Givianrad M, Aberoomand-Azar P, Waqif-Husain S, Jafari Mohammadi S. Chemical composition of Iran’s pistacia atlantica cold-pressed oil. J Chem. 2012; 2013(7):1-6.
  19. Wani FA, Albahrawy AZ, Rahiman S. Hypolipidemic activity of olive oil (olea europaea) against high fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice. Open Journal of Pathology. 2015;5(03):73.
  20. Barbosa C, Albuquerque E, Faria E, Oliveira H, Castilho L. Opposite lipemic response of Wistar rats and C57BL/6 mice to dietary glucose or fructose supplementation. Braz J Med Biol Res. 2007;40(3):323-31.
  21. Maedler K, Oberholzer J, Bucher P, Spinas GA, Donath MY. Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic β-cell turnover and function. Diabetes. 2003;52(3):726-33.
  22. Parillo M, Rivellese A, Ciardullo A, Capaldo B, Giacco A, Genovese S, et al. A high-monounsaturated-fat/low-carbohydrate diet improves peripheral insulin sensitivity in non-insulin-dependent diabetic patients. Metabolism. 1992;41(12):1373-8.
  23. Rocca AS, LaGreca J, Kalitsky J, Brubaker PL. Monounsaturated fatty acid diets improve glycemic tolerance through increased secretion of glucagon-like peptide-1. Endocrinology. 2001;142(3):1148-55.
  24. Garg A. High-monounsaturated-fat diets for patients with diabetes mellitus: a meta-analysis. Am J Clin Nutr. 1998;67(3):577S-82S.
  25. Ryan M, McInerney D, Owens D, Collins P, Johnson A, Tomkin G. Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity. QJM. 2000;93(2):85-91.
  26. Maritim A, Sanders a, Watkins J, 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17(1):24-38.
  27. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004;24(5):816-23.
  28. Coppey LJ, Gellett JS, Davidson EP, Dunlap JA, Lund DD, Yorek MA. Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity of epineurial arterioles of the sciatic nerve. Diabetes. 2001;50(8):1927-37.
  29. Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA, Tapsell LC, et al. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia. 2001;44(3):312-9.
  30. Fakour S, Heydari S, Akradi L, Rahymi Bane R. Effect of Pistacia atlantica Mastic Extract on Experimental Wound Healing and Various Biochemical Parameters of Blood Serum in Rabbit Models. Journal of Medicinal Plants. 2017;3(63):78-91.
  31. Mohammadi Karizno F, Saghebjoo M, Foadoddini M, Sarir H. The role of aerobic training and Pistacia atlantica extract on the levels of protein carbonyl, heat shock protein 70, and glycogen in the liver tissue of diabetic rats. Journal of Birjand University of Medical Sciences. 2014;21(1):35-47.
  32. Tolooei M, Mirzaei A. Effects of Pistacia Atlantica extract on erythrocyte membrane rigidity, oxidative stress, and hepatotoxicity induced by CCl4 in rats. Glob J Health Sci. 2015;7(7):32.
  33. Djerroua Z, Hamdi-Pacha Y, Belkhiri A, Djaalab H, Riachia F, Serakta M, et al. Evaluation of Pistacia lentiscus fatty oil effects on glycemic index, liver functions and kidney functions of New Zealand rabbits. Afr J Tradit Complement Altern Med. 2011;8(5S).