Vol 80, No 1 (2021)
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Published online: 2020-03-18

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Ameliorating effect of pomegranate peel extract supplement against type 1 diabetes-induced hepatic changes in the rat: biochemical, morphological and ultrastructural microscopic studies

K A.J. Faddladdeen1
Pubmed: 32207851
Folia Morphol 2021;80(1):149-157.

Abstract

Background: Diabetes mellitus could result from disorders in insulin secretion or receptors mainly characterised by hyperglycaemia. Natural antioxidants including pomegranate are traditionally used as hypoglycaemic agents. The present research was designed to evaluate the possible therapeutic role of pomegranate peel extract (PPE) against type 1 diabetic-induced hepatic biochemical and histological alteration.

Materials and methods: Adult male Wistar rats (n = 48) were sorted into four groups: G1: control group, G2: normal rats received PPE, G3: streptozotocin (STZ)-diabetic rats, received IP STZ (55 mg/kg body weight), and G4: diabetic rats post-treated with PPE (200 mg/kg body weight/day). Effectiveness of PPE was assessed by measuring serum glucose, liver enzymes, and morphological features of liver tissue using light and electron microscopy.

Results: Histological examination showed degenerative necrotic changes in diabetic rat liver which were improved by post-treatment with PPE. Biochemical results confirmed microscopic morphological and ultrastructural findings.

Conclusions: Pomegranate peel extract was found to have a moderate therapeutic effect against hepatic alterations in male rats. It could be advised for diabetic patients suffering from early alterations of liver functions.

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References

  1. Aboonabi A, Rahmat A, Othman F. Effect of pomegranate on histopathology of liver and kidney on generated oxidative stress diabetic induced rats. J Cytol Histol. 2015; 6(1).
  2. Ahmadieh H, Azar ST. Liver disease and diabetes: association, pathophysiology, and management. Diabetes Res Clin Pract. 2014; 104(1): 53–62.
  3. Ahmed RR, Abdul-Hamid M, Galaly SR, et al. Monosodium glutamate-induced liver microscopic and biochemical changes in male rats, and the possible amendment of quercetin. Egypt J Zoo. 2019; 71(71): 44–55.
  4. Akhtar S, Ismail T, Layla A. Pomegranate bioactive molecules and health benefits. Bioactive Molecules Food. 2019: 1253–1279.
  5. Al-Attar AM, Alsalmi FA. Influence of olive leaves extract on hepatorenal injury in streptozotocin diabetic rats. Saudi J Biol Sci. 2019; 26(7): 1865–1874.
  6. Alejandra Sánchez-Muñoz M, Valdez-Solana MA, Campos-Almazán MI, et al. Streptozotocin-Induced adaptive modification of mitochondrial supercomplexes in liver of wistar rats and the protective effect of lam. Biochem Res Int. 2018; 2018: 5681081.
  7. Alshathly MR. Efficacy of ginger (zingiber officinale) in ameliorating streptozotocin-induced diabetic liver injury in rats: histological and biochemical studies. J Microsc Ultrastruct. 2019; 7(2): 91–101.
  8. Althunibat O, Al-Mustafa A, Tarawneh K, et al. Protective role of Punica granatum L. peel extract against oxidative damage in experimental diabetic rats. Proc Biochem. 2010; 45(4): 581–585.
  9. Ardekani MRS, Hajimahmoodi M, Oveisi MR, et al. Comparative antioxidant activity and total flavonoid content of Persian pomegranate (Punica granatum L.) cultivars. Iran J pharmaceut Research: IJPR. 2011; 10(3): 519.
  10. Arruda AP, Hotamisligil GS. Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes. Cell Metab. 2015; 22(3): 381–397.
  11. Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-A concise review. Saudi Pharm J. 2016; 24(5): 547–553.
  12. Bae JS, Lee JY, Lee DH, et al. Quantitative evaluation of hepatic steatosis using normalized local variance in a rat model: comparison with histopathology as the reference standard. Korean J Radiol. 2019; 20(9): 1399–1407.
  13. Chang JYA, Yu F, Shi L, et al. Melatonin affects mitochondrial fission/fusion dynamics in the diabetic retina. J Diabetes Res. 2019; 2019: 8463125.
  14. Czajka A, Malik AN. Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy. Redox Biol. 2016; 10: 100–107.
  15. Duru OK, Middleton T, Tewari MK, et al. The landscape of diabetic kidney disease in the united states. Curr Diab Rep. 2018; 18(3): 14.
  16. El-Hadary AE, Ramadan MF. Phenolic profiles, antihyperglycemic, antihyperlipidemic, and antioxidant properties of pomegranate (Punica granatum) peel extract. J Food Biochem. 2019; 43(4): e12803.
  17. Faddladdeen KA, Ojaimi AA. Protective effect of pomegranate (Punica granatum) extract against diabetic changes in adult male rat liver: histological study. J Microsc Ultrastruct. 2019; 7(4): 165–170.
  18. Farid O, Zeggwagh NA, Ouadi FEl, et al. aqueous extract exhibits antidiabetic and hepatoprotective effects in streptozotocin-induced diabetic rats. Endocr Metab Immune Disord Drug Targets. 2019; 19(3): 292–301.
  19. Ferrell JM, Chiang JYL. Circadian rhythms in liver metabolism and disease. Acta Pharm Sin B. 2015; 5(2): 113–122.
  20. George B, Cebioglu M, Yeghiazaryan K. Inadequate diabetic care: global figures cry for preventive measures and personalized treatment. EPMA J. 2010; 1(1): 13–18.
  21. Gheorghe G, Stoian A, Gaman MA, et al. The benefits and risks of antioxidant treatment in liver diseases. Revista de Chimie. 2019; 70(2): 651–655.
  22. Hou C, Zhang W, Li J, et al. Beneficial effects of pomegranate on lipid metabolism in metabolic disorders. Mol Nutr Food Res. 2019; 63(16): e1800773.
  23. Jurenka JS. Therapeutic applications of pomegranate (Punica granatum L.): a review. Altern Med Rev. 2008; 13(2): 128–144.
  24. Khaled SA. Herbal medicine in diabetes mellitus: effectiveness of punica granatum peel powder in prediabetics, diabetics and complicated diabetics. J Biol Agriculture Healthcare. 2015; 5(16): 34–42.
  25. Lisha V, John P, Sujith S, et al. Effect of Averrhoa bilimbi fruit powder on Histopathology and the functional Indices of the Liver and Kidney of Rats fed with high fat diet. Pharma Innov J. 2019; 8(1): 48–51.
  26. Lucchesi AN, Cassettari LL, Spadella CT. Alloxan-induced diabetes causes morphological and ultrastructural changes in rat liver that resemble the natural history of chronic fatty liver disease in humans. J Diabetes Res. 2015; 2015: 494578.
  27. Mahmoud A, Elgheri A, Shakor AA. Hyperglycemia and hyperinsulinemia induced hepatocellular autophagy in male mice. Egypt Acad J Biol Sci, D. Histology Histochemistry. 2015; 7(1): 1–10.
  28. Manna K, Mishra S, Saha M, et al. Amelioration of diabetic nephropathy using pomegranate peel extract-stabilized gold nanoparticles: assessment of NF-κB and Nrf2 signaling system. Int J Nanomedicine. 2019; 14: 1753–1777.
  29. Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003; 17(1): 24–38.
  30. Masarone M, Rosato V, Dallio M, et al. Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease. Oxid Med Cell Longev. 2018; 2018: 9547613.
  31. Mielańczyk Ł, Matysiak N, Klymenko O, et al. Transmission electron microscopy of biological samples. Transmission Electron Microscope - Theory Applications. 2015.
  32. Mohammad G, Duraisamy AJ, Kowluru A, et al. Functional regulation of an oxidative stress mediator, rac1, in diabetic retinopathy. Mol Neurobiol. 2019; 56(12): 8643–8655.
  33. Nadia M, Ramadan G, El-Husseiny E, et al. Effects of pomegranate aril juice and its punicalagin on some key regulators of insulin resistance and oxidative liver injury in streptozotocin-nicotinamide type 2 diabetic rats. Mol Biol Rep. 2019; 46(4): 3701–3711.
  34. Nagarajan SR, Paul-Heng M, Krycer JR, et al. Lipid and glucose metabolism in hepatocyte cell lines and primary mouse hepatocytes: a comprehensive resource for in vitro studies of hepatic metabolism. Am J Physiol Endocrinol Metab. 2019; 316(4): E578–E589.
  35. Papaccio G, Pisanti F, Latronico M, et al. Multiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide. J Cell Biochem. 2000; 77(1): 82–91, doi: 10.1002/(sici)1097-4644(20000401)77:1<82::aid-jcb9>3.0.co;2-v.
  36. Qin H, Chen H, Zou Y, et al. Systematic investigation of the mechanism of Cichorium glandulosum on type 2 diabetes mellitus accompanied with non-alcoholic fatty liver rats. Food Funct. 2019; 10(5): 2450–2460.
  37. Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963; 17: 208–212.
  38. Rodríguez V, Plavnik L, Tolosa de Talamoni N. Naringin attenuates liver damage in streptozotocin-induced diabetic rats. Biomed Pharmacother. 2018; 105: 95–102.
  39. Rogers RS, Wheatley JL, Archer AE, et al. Heat shock protein 72 regulates mitochondrial integrity and function in the prevention of hepatic insulin resistance. FASEB J 30(1_supplement. 2016; 30(suppl 1): 1015–1011.
  40. Saad EA, Hassanien MM, El-Hagrasy MA, et al. Antidiabetic, hypolipidemic and antioxidant activities and protective effects of Punica granatum peels powder against pancreatic and hepatic tissues injuries in streptozotocin induced IDDM in rats. Int J Pharm Pharm Sci. 2015; 7(7): 397–402.
  41. Salwe KJ, Sachdev DO, Bahurupi Y, et al. Evaluation of antidiabetic, hypolipedimic and antioxidant activity of hydroalcoholic extract of leaves and fruit peel of Punica granatum in male Wistar albino rats. J Nat Sci Biol Med. 2015; 6(1): 56–62.
  42. Seng YH, Chang CW, Chiang W, et al. Adlay bran oil suppresses hepatic gluconeogenesis and attenuates hyperlipidemia in type 2 diabetes rats. J Med Food. 2019; 22(1): 22–28.
  43. Shaw JP, Moore MN, Readman JW, et al. Oxidative stress, lysosomal damage and dysfunctional autophagy in molluscan hepatopancreas (digestive gland) induced by chemical contaminants. Mar Environ Res. 2019; 152: 104825.
  44. Smith BW, Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol. 2011; 7(8): 456–465.
  45. Song D, Yin L, Wang C, et al. Adenovirus-mediated expression of SIK1 improves hepatic glucose and lipid metabolism in type 2 diabetes mellitus rats. PloS One. 2019; 14(6): e0210930.
  46. Targher G, Lonardo A, Byrne CD. Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol. 2018; 14(2): 99–114.
  47. Vučić V, Grabež M, Trchounian A, et al. Composition and potential health benefits of pomegranate: a review. Curr Pharm Des. 2019; 25(16): 1817–1827.
  48. Zhang C, Hu J, Sheng L, et al. Ellagic acid ameliorates AKT-driven hepatic steatosis in mice by suppressing de novo lipogenesis via the AKT/SREBP-1/FASN pathway. Food Funct. 2019; 10(6): 3410–3420.
  49. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018; 14(2): 88–98.
  50. Zhou Bh, Zhao J, Liu J, et al. Fluoride-induced oxidative stress is involved in the morphological damage and dysfunction of liver in female mice. Chemosphere. 2015; 139: 504–511.
  51. Zhou B, Li Q, Wang J, et al. Ellagic acid attenuates streptozocin induced diabetic nephropathy via the regulation of oxidative stress and inflammatory signaling. Food Chem Toxicol. 2019; 123: 16–27.