Diyabet ve postmenopozal sıçanları birleştiren ikili durum modelinde Myrtus communis'in gastroprotektif rolü: östrojen tedavisi ile karşılaştırılabilir sonuçlar
Yıl 2025,
Cilt: 50 Sayı: 2, 420 - 434, 30.06.2025
Eda Dağsuyu
,
Süha Beril Kadıoğlu Yaman
,
Ali Şen
,
Göksel Şener
,
Refiye Yanardağ
Öz
Amaç: Menopoz sırasındaki hormonal değişiklikler, özellikle östrojen ve progesteron seviyelerindeki düşüş, sindirimi yavaşlatarak gastrointestinal işlevi bozabilir. Bu çalışma, Myrtus communis subsp. communis (MC) özütünün postmenopozal diyabetik sıçan modelinde gastrik doku üzerindeki koruyucu etkilerini değerlendirmeyi ve etkinliğini östrojen (E2) tedavisiyle karşılaştırmayı amaçlamaktadır.
Gereç ve Yöntem: Dişi Sprague-Dawley sıçanları altı gruba ayrıldı: kontrol (C); overektomi (OVX); diyabet (D); overektomi ve diyabet (OVX+D); overektomi, diyabet ve östrojen (OVX+D+E2); overektomi, diyabet ve MC (OVX+D+MC). OVX grupları, çift dorsolateral yöntemi kullanarak bilateral overektomiye tabi tutuldu. Yedi günlük iyileşme süresinin ardından, streptozotosin kullanılarak diyabet oluşturuldu. OVX+D+E2 ve OVX+D+MC gruplarına sırasıyla 10 µg/kg s.c. E2 ve 100 mg/kg p.o. MC ekstresi dört hafta süreyle uygulandı. Mide dokusu biyokimyasal parametreler açısından analiz edildi.
Bulgular: OVX, D ve OVX+D, C grubuna kıyasla antioksidan enzim aktivitelerinde ve glutatyon seviyelerinde önemli azalmalar ve oksidatif stres belirteçlerinde ve lipid peroksidasyonunda artışlar gösterdi. E2 ve MC tedavileri bu olumsuz değişiklikleri etkili bir şekilde hafifletti ve MC, birçok parametrede E2 ile karşılaştırılabilir veya daha üstün etkiler gösterdi. MC tedavisi kan glikoz seviyelerini (OVX+D'de ~%60 azalma), ve mide dokusundaki Na+/K+-ATPaz aktivitesini (OVX+D'de ~%110 artış) ve glikoproteinlerin seviyelerini önemli ölçüde iyileştirdi.
Sonuç: MC özütü, E2 tedavisiyle kıyaslanabilecek şekilde, menopoz sonrası diyabetli sıçanlarda güçlü antioksidan ve gastroprotektif etkiler göstermektedir. Bu bulgular, MC’nin menopoz ve diyabetle ilişkili gastrik komplikasyonları yönetmek için doğal bir terapötik ajan olarak potansiyelini vurgulamaktadır.
Kaynakça
- Aykac A, Ozbeyli D, Uncu M, Ertaş B, Kılınc O, Şen A et al. Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors. Gene. 2019;689:194–201.
- Kadıoğlu Yaman B, Çevik Ö, Yalman K, Ertaş B, Şen A, Şener G. Myrtus communis subsp. communis improved cognitive functions in ovariectomized diabetic rats. Gene. 2020;744:144616.
- Gorjian H, Khaligh NG. Myrtle: A versatile medicinal plant. Nutrire. 2023;48:10.
- Jabri M-A, Marzouki L, Sebai H. Ethnobotanical, phytochemical and therapeutic effects of Myrtus communis L. berries seeds on gastrointestinal tract diseases: A review. Arch Physiol Biochem. 2018;124:390–6.
- Hennia A, Nemmiche S, Dandlen S, Miguel MG. Myrtus communis essential oils: Insecticidal, antioxidant and antimicrobial activities: A review. J Essent Oil Res. 2019;31:487–545.
- Kashyap P, Farrugia G. Oxidative stress: Key player in gastrointestinal complications of diabetes. J Neurogastroenterol Motil. 2011;23:111–4.
- Young CF, Moussa M, Shubrook JH. Diabetic gastroparesis: A review. Diabetes Spectr. 2020;33:290–7.
- Lurati AR. Effects of menopause on appetite and the gastrointestinal system. Nurs Womens Health. 2018;22:499–505.
- Leanza G, Conte C, Cannata F, Isgrò C, Piccoli A, Strollo R et al. Oxidative stress in postmenopausal women with or without obesity. Cells. 2023;12:1137.
- Park SB, Kim CH, Hong M, Yang H-J, Chung CK. Effect of a selective estrogen receptor modulator on bone formation in osteoporotic spine fusion using an ovariectomized rat model. Spine J. 2016;16:72–81.
- Beutler E. Reduced Glutathione (GSH). In: In: Bergmeyen, H.V., Ed., Red Blood Cell Metabolism: A Manual of Biochemical Methods, 2nd Edition, Grune and Stratton, New York. 1975:112–4.
- Ledwozyw A, Michalak J, Stȩpień A, Ka̧dziołka A. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chim Acta. 1986;155:275–83.
- Beutler E. Red Cell Metabolism. A Manuel of Biochemical Methods. 12th ed.; 1971.
- Habig WH, Jakoby WB. Assays for differentiation of glutathione S-transferases. Methods Enzymol. 1981;77:398–405.
- Wendel A. Glutathione peroxidase. Methods Enzymol. 1981;77:325–33.
- Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6.
- Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986;82:512–20.
- Bais R, Philcox M. Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 8. IFCC Method for Lactate Dehydrogenase (l-Lactate: NAD+Oxidoreductase, EC 1.1.1.27). International Federation of Clinical Chemistry (IFCC). Eur J Clin Chem Clin Biochem. 1994;32:639–55.
- Beutler E. Red blood cell metabolism: A Manual of Biochemical Methods. 3nd Edition, Orlando, Grune and Stratton 1984:68–70.
- Verpoorte JA, Mehta S, Edsall JT. Esterase activities of human carbonic anhydrases B and C. J Biol Chem. 1967;242:4221–9.
- Corte ED, Stirpe F. Regulation of xanthine oxidase in rat liver: Modifications of the enzyme activity of rat liver supernatant on storage at 20 degrees. Biochem J. 1968;108:349–51.
- Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464–78.
- Ridderstap A, Bonting S. Na+- K+-activated ATPase anc exocrine pancreatic secretion in vitro. Am J Physiol Content. 1969;217:1721–7.
- Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5:62–71.
- Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29:225–9.
- Zhang Y, Chen J, Ji H, Xiao ZG, Shen P, Xu LH. Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model. BMC Complement Altern Med. 2018;18:343.
- Burton K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956;62:315–23.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–75.
- Lorentz K, Weiss T, Kraas E. Sialic acid in human serum and cerebrospinal fluid: comparison of methods and reference values. Clin Chem Lab Med. 1986;24:189–98.
- Dische Z, Shettles LB. A specific color reaction of methylpentoses and a spectrophotometric micromethod for their determination. J Biol Chem. 1948;175:595–603.
- Winzler RJ. Determination of serum glycoproteins. In: In: Glick DP (Ed) Methods of Biochemical Analysis. Interscience Publisher Inc, New York, 1955:279-311.
- Ribas V, Nguyen MTA, Henstridge DC, Nguyen A-K, Beaven SW, Watt MJ et al. Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice. Am J Physiol Metabol. 2010;298:E304–19.
- Samy DM, Mostafa DK, Saleh SR, Hassaan PS, Zeitoun TM, Ammar GAG et al. Carnosic acid mitigates depression-like behavior in ovariectomized mice via activation of Nrf2/HO-1 pathway. Mol Neurobiol. 2023;60:610–28.
- Pereira P, Cebola M-J, Oliveira MC, Bernardo Gil MG. Antioxidant capacity and identification of bioactive compounds of Myrtus communis L. extract obtained by ultrasound-assisted extraction. J Food Sci Technol. 2017;54:4362–9.
- Jabri M-A, Rtibi K, Tounsi H, Hosni K, Marzouki L, Sakly M et al. Fatty acid composition and mechanisms of the protective effects of myrtle berry seed aqueous extract in alcohol-induced peptic ulcer in rat. Can J Physiol Pharmacol. 2017;95:510–21.
- Zhang Q, Song X, Chen X, Jiang R, Peng K, Tang X et al. Antiosteoporotic effect of hesperidin against ovariectomy‐induced osteoporosis in rats via reduction of oxidative stress and inflammation. J Biochem Mol Toxicol. 2021;35:e22832.
- Ha BJ. Oxidative stress in ovariectomy menopause and role of chondroitin sulfate. Arch Pharm Res. 2004;27:867–72.
- Sankar P, Zachariah B, Vickneshwaran V, Jacob SE, Sridhar MG. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: The molecular mechanisms. Exp Gerontol. 2015;63:67–75.
- Tian X, Gao Z, Yin D, Hu Y, Fang B, Li C et al. 17beta-estradiol alleviates contusion-induced skeletal muscle injury by decreasing oxidative stress via SIRT1/PGC-1α/Nrf2 pathway. Steroids. 2023;191:109160.
- Ltaif M, Gargouri M, Soussi A. Protective effects of A. sativa against oxidative stress-induced liver damage in ovariectomized mice. Biomed Res Int. 2021;2021:1–15.
- Oliveira MC de, Campos-Shimada LB, Marçal-Natali MR, Ishii-Iwamoto EL, Salgueiro-Pagadigorria CL. A long-term estrogen deficiency in ovariectomized mice is associated with disturbances in fatty acid oxidation and oxidative stress. RBGO Gynecol Obstet. 2018;40:251–9.
- Barker KL. Mechanisms of regulation of uterine enzyme levels by estradiol. In: The Endometrium. Dordrecht: Springer Netherlands; 1980:227–46.
- Obradovic M, Bjelogrlic P, Rizzo M, Katsiki N, Haidara M, Stewart AJ et al. Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases. J Endocrinol. 2013;218:13–23.
- Liu C-G, Xu K-Q, Xu X, Huang J-J, Xiao J-C, Zhang J-P et al. 17β-Oestradiol regulates the expression of Na+/K+-ATPase β1-subunit, sarcoplasmic reticulum Ca2+-ATPase and carbonic anhydrase iv in H9C2 cells. Clin Exp Pharmacol Physiol. 2007;34:998–1004.
- Ribon-Demars A, Pialoux V, Boreau A, Marcouiller F, Larivière R, Bairam A et al. Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia. Acta Physiol. 2019;225:e13159.
- Hayder N, Bouhlel I, Skandrani I, Kadri M, Steiman R, Guiraud P et al. In vitro antioxidant and antigenotoxic potentials of myricetin-3-o-galactoside and myricetin-3-o-rhamnoside from Myrtus communis: Modulation of expression of genes involved in cell defence system using cDNA microarray. Toxicol in Vitro. 2008;22:567–81.
- Hecker M, Wagner AH. Role of protein carbonylation in diabetes. J Inherit Metab Dis. 2018;41:29–38.
- Turkyilmaz İ, Yanardağ R. Antioxidants prevent indomethacin-induced oxidative damage in tongue tissues of rats. İstanbul Journal of Pharmacy. 2023;53:73–9.
- Karatuğ Kaçar A, Ertik O, Coşkun Yazıcı Z, Bolkent S, Yanardağ R, Bolkent Ş. The combined ameliorative effects of α-lipoic acid, selenium, and vitamin E on the livers of STZ-diabetic mice. İstanbul Journal of Pharmacy. 2023;53:199–210.
- Ben Hsouna A, Dhibi S, Dhifi W, Mnif W, Ben Nasr hmed, Hfaiedh N. Chemical composition and hepatoprotective effect of essential oil from Myrtus communis L. flowers against CCL 4 -induced acute hepatotoxicity in rats. RSC Adv. 2019;9:3777–87.
- Yamaguchi M, Kishi S. Prolonged administration of β-alanyl-L-histidinato zinc prevents bone loss in ovariectomized rats. Jpn J Pharmacol. 1993;63:203–7.
- Paradise WA, Vesper BJ, Goel A, Waltonen JD, Altman KW, Haines GK et al. Nitric oxide: Perspectives and emerging studies of a well known cytotoxin. Int J Mol Sci. 2010;11:2715–45.
- Sokolovska J, Dekante A, Baumane L, Pahirko L, Valeinis J, Dislere K. et al. Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy. Biomed Rep. 2020;12:251–8.
- Bayrak B, Mahmarzayeva D, Türkyılmaz İ, Saçan Ö, Yanardağ R. The protective effects of S-methyl methionine sulfonium chloride on brain tissue damage in D-galactosamine-induced hepatotoxicity. Experimed. 2022;12:38–43.
- Paape MJ, Sinha YN. Nucleic acid and collagen content of mammary glands between 30 and 80 days of age in normal and ovariectomized rats and during pregnancy. J Dairy Sci. 1971;54:1068–74.
- Tas S, Tas B, Bassalat N, Jaradat N. In-vivo, hypoglycemic, hypolipidemic and oxidative stress inhibitory activities of Myrtus communis L. fruits hydroalcoholic extract in normoglycemic and streptozotocin-induced diabetic rats. Biomed Res. 2018;29:2727–34.
- Magaji UF, Miftari S, Saçan Ö, Yanardağ R. Effect of antiepileptic drug sodium valproate on stomach tissue glycoproteins: The protective role of Moringa extract. Arch Epilepsy. 2023;29:41–5.
- Sacan O, Turkyilmaz IB, Bayrak BB, Mutlu O, Akev N, Yanardag R. Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats. BioMetals. 2016;29:239–48.
- Turkyilmaz IB, Altas N, Arisan I, Yanardag R. Effect of vitamin B-6 on brain damage in valproic acid induced toxicity. J Biochem Mol Toxicol. 2021;35:e22855.
- Ertik O, Sener G, Yanardag R. The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes. J Biochem Mol Toxicol. 2023;37.
- Niki E, Nakano M. Estrogens as antioxidants. Methods Enzymol. 1990;186:330–3.
- Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó F V, Viña J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med. 2003;34:546–52.
Gastroprotective role of Myrtus communis in a dual-condition model combining diabetes and postmenopausal rats: comparable outcomes to estrogen therapy
Yıl 2025,
Cilt: 50 Sayı: 2, 420 - 434, 30.06.2025
Eda Dağsuyu
,
Süha Beril Kadıoğlu Yaman
,
Ali Şen
,
Göksel Şener
,
Refiye Yanardağ
Öz
Purpose: Hormonal changes during menopause, especially the decline in estrogen and progesterone levels, can impair gastrointestinal function by slowing digestion. This study aimed to evaluate the protective effects of Myrtus communis subsp. communis (MC) extract on gastric tissue in a postmenopausal diabetic rat model and to compare its efficacy with estrogen (E2) treatment.
Materials and Methods: Female Sprague-Dawley rats were divided into six groups: control (C); ovariectomy (OVX); diabetes (D); ovariectomy and diabetes (OVX+D); ovariectomy, diabetes and estrogen (OVX+D+E2); ovariectomy, diabetes and MC (OVX+D+MC). OVX groups had bilateral ovariectomy utilizing the double dorsolateral method. After a seven-day recovery, diabetes was induced using streptozotocin. OVX+D+E2 and OVX+D+MC groups were treated with 10 µg/kg s.c. E2 and 100 mg/kg p.o. MC extract, respectively, for four weeks. Stomach tissues were analyzed for biochemical parameters.
Results: The OVX, D, and OVX+D showed significant reductions in antioxidant enzyme activities and glutathione levels, and increases in oxidative stress markers and lipid peroxidation compared to the C group. E2 and MC treatments effectively mitigated these alterations, with MC showing comparable or superior effects to E2 in many parameters. MC treatment significantly improved blood glucose levels (~60% reduction in the OVX+D), stomach Na+/K+-ATPase activity (~110% increase in the OVX+D), and glycoprotein component levels.
Conclusion: MC extract exhibits potent antioxidant and gastroprotective effects in postmenopausal diabetic rats, comparable to E2 treatment. These findings highlight its potential as a natural therapeutic agent for managing menopause- and diabetes-associated gastric complications.
Etik Beyan
All animals were obtained from the Marmara University Experimental Animal Implementation and Research Centre. The experimental protocols were approved by the Marmara University Local Ethics Committee for Animal Experiments (Protocol number: 42.2023.mar, dated 15.08.2023), and conducted in accordance with institutional guidelines and the ARRIVE reporting standards.
Kaynakça
- Aykac A, Ozbeyli D, Uncu M, Ertaş B, Kılınc O, Şen A et al. Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors. Gene. 2019;689:194–201.
- Kadıoğlu Yaman B, Çevik Ö, Yalman K, Ertaş B, Şen A, Şener G. Myrtus communis subsp. communis improved cognitive functions in ovariectomized diabetic rats. Gene. 2020;744:144616.
- Gorjian H, Khaligh NG. Myrtle: A versatile medicinal plant. Nutrire. 2023;48:10.
- Jabri M-A, Marzouki L, Sebai H. Ethnobotanical, phytochemical and therapeutic effects of Myrtus communis L. berries seeds on gastrointestinal tract diseases: A review. Arch Physiol Biochem. 2018;124:390–6.
- Hennia A, Nemmiche S, Dandlen S, Miguel MG. Myrtus communis essential oils: Insecticidal, antioxidant and antimicrobial activities: A review. J Essent Oil Res. 2019;31:487–545.
- Kashyap P, Farrugia G. Oxidative stress: Key player in gastrointestinal complications of diabetes. J Neurogastroenterol Motil. 2011;23:111–4.
- Young CF, Moussa M, Shubrook JH. Diabetic gastroparesis: A review. Diabetes Spectr. 2020;33:290–7.
- Lurati AR. Effects of menopause on appetite and the gastrointestinal system. Nurs Womens Health. 2018;22:499–505.
- Leanza G, Conte C, Cannata F, Isgrò C, Piccoli A, Strollo R et al. Oxidative stress in postmenopausal women with or without obesity. Cells. 2023;12:1137.
- Park SB, Kim CH, Hong M, Yang H-J, Chung CK. Effect of a selective estrogen receptor modulator on bone formation in osteoporotic spine fusion using an ovariectomized rat model. Spine J. 2016;16:72–81.
- Beutler E. Reduced Glutathione (GSH). In: In: Bergmeyen, H.V., Ed., Red Blood Cell Metabolism: A Manual of Biochemical Methods, 2nd Edition, Grune and Stratton, New York. 1975:112–4.
- Ledwozyw A, Michalak J, Stȩpień A, Ka̧dziołka A. The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis. Clin Chim Acta. 1986;155:275–83.
- Beutler E. Red Cell Metabolism. A Manuel of Biochemical Methods. 12th ed.; 1971.
- Habig WH, Jakoby WB. Assays for differentiation of glutathione S-transferases. Methods Enzymol. 1981;77:398–405.
- Wendel A. Glutathione peroxidase. Methods Enzymol. 1981;77:325–33.
- Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6.
- Mylroie AA, Collins H, Umbles C, Kyle J. Erythrocyte superoxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986;82:512–20.
- Bais R, Philcox M. Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 8. IFCC Method for Lactate Dehydrogenase (l-Lactate: NAD+Oxidoreductase, EC 1.1.1.27). International Federation of Clinical Chemistry (IFCC). Eur J Clin Chem Clin Biochem. 1994;32:639–55.
- Beutler E. Red blood cell metabolism: A Manual of Biochemical Methods. 3nd Edition, Orlando, Grune and Stratton 1984:68–70.
- Verpoorte JA, Mehta S, Edsall JT. Esterase activities of human carbonic anhydrases B and C. J Biol Chem. 1967;242:4221–9.
- Corte ED, Stirpe F. Regulation of xanthine oxidase in rat liver: Modifications of the enzyme activity of rat liver supernatant on storage at 20 degrees. Biochem J. 1968;108:349–51.
- Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464–78.
- Ridderstap A, Bonting S. Na+- K+-activated ATPase anc exocrine pancreatic secretion in vitro. Am J Physiol Content. 1969;217:1721–7.
- Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5:62–71.
- Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29:225–9.
- Zhang Y, Chen J, Ji H, Xiao ZG, Shen P, Xu LH. Protective effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model. BMC Complement Altern Med. 2018;18:343.
- Burton K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956;62:315–23.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–75.
- Lorentz K, Weiss T, Kraas E. Sialic acid in human serum and cerebrospinal fluid: comparison of methods and reference values. Clin Chem Lab Med. 1986;24:189–98.
- Dische Z, Shettles LB. A specific color reaction of methylpentoses and a spectrophotometric micromethod for their determination. J Biol Chem. 1948;175:595–603.
- Winzler RJ. Determination of serum glycoproteins. In: In: Glick DP (Ed) Methods of Biochemical Analysis. Interscience Publisher Inc, New York, 1955:279-311.
- Ribas V, Nguyen MTA, Henstridge DC, Nguyen A-K, Beaven SW, Watt MJ et al. Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERα-deficient mice. Am J Physiol Metabol. 2010;298:E304–19.
- Samy DM, Mostafa DK, Saleh SR, Hassaan PS, Zeitoun TM, Ammar GAG et al. Carnosic acid mitigates depression-like behavior in ovariectomized mice via activation of Nrf2/HO-1 pathway. Mol Neurobiol. 2023;60:610–28.
- Pereira P, Cebola M-J, Oliveira MC, Bernardo Gil MG. Antioxidant capacity and identification of bioactive compounds of Myrtus communis L. extract obtained by ultrasound-assisted extraction. J Food Sci Technol. 2017;54:4362–9.
- Jabri M-A, Rtibi K, Tounsi H, Hosni K, Marzouki L, Sakly M et al. Fatty acid composition and mechanisms of the protective effects of myrtle berry seed aqueous extract in alcohol-induced peptic ulcer in rat. Can J Physiol Pharmacol. 2017;95:510–21.
- Zhang Q, Song X, Chen X, Jiang R, Peng K, Tang X et al. Antiosteoporotic effect of hesperidin against ovariectomy‐induced osteoporosis in rats via reduction of oxidative stress and inflammation. J Biochem Mol Toxicol. 2021;35:e22832.
- Ha BJ. Oxidative stress in ovariectomy menopause and role of chondroitin sulfate. Arch Pharm Res. 2004;27:867–72.
- Sankar P, Zachariah B, Vickneshwaran V, Jacob SE, Sridhar MG. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: The molecular mechanisms. Exp Gerontol. 2015;63:67–75.
- Tian X, Gao Z, Yin D, Hu Y, Fang B, Li C et al. 17beta-estradiol alleviates contusion-induced skeletal muscle injury by decreasing oxidative stress via SIRT1/PGC-1α/Nrf2 pathway. Steroids. 2023;191:109160.
- Ltaif M, Gargouri M, Soussi A. Protective effects of A. sativa against oxidative stress-induced liver damage in ovariectomized mice. Biomed Res Int. 2021;2021:1–15.
- Oliveira MC de, Campos-Shimada LB, Marçal-Natali MR, Ishii-Iwamoto EL, Salgueiro-Pagadigorria CL. A long-term estrogen deficiency in ovariectomized mice is associated with disturbances in fatty acid oxidation and oxidative stress. RBGO Gynecol Obstet. 2018;40:251–9.
- Barker KL. Mechanisms of regulation of uterine enzyme levels by estradiol. In: The Endometrium. Dordrecht: Springer Netherlands; 1980:227–46.
- Obradovic M, Bjelogrlic P, Rizzo M, Katsiki N, Haidara M, Stewart AJ et al. Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases. J Endocrinol. 2013;218:13–23.
- Liu C-G, Xu K-Q, Xu X, Huang J-J, Xiao J-C, Zhang J-P et al. 17β-Oestradiol regulates the expression of Na+/K+-ATPase β1-subunit, sarcoplasmic reticulum Ca2+-ATPase and carbonic anhydrase iv in H9C2 cells. Clin Exp Pharmacol Physiol. 2007;34:998–1004.
- Ribon-Demars A, Pialoux V, Boreau A, Marcouiller F, Larivière R, Bairam A et al. Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia. Acta Physiol. 2019;225:e13159.
- Hayder N, Bouhlel I, Skandrani I, Kadri M, Steiman R, Guiraud P et al. In vitro antioxidant and antigenotoxic potentials of myricetin-3-o-galactoside and myricetin-3-o-rhamnoside from Myrtus communis: Modulation of expression of genes involved in cell defence system using cDNA microarray. Toxicol in Vitro. 2008;22:567–81.
- Hecker M, Wagner AH. Role of protein carbonylation in diabetes. J Inherit Metab Dis. 2018;41:29–38.
- Turkyilmaz İ, Yanardağ R. Antioxidants prevent indomethacin-induced oxidative damage in tongue tissues of rats. İstanbul Journal of Pharmacy. 2023;53:73–9.
- Karatuğ Kaçar A, Ertik O, Coşkun Yazıcı Z, Bolkent S, Yanardağ R, Bolkent Ş. The combined ameliorative effects of α-lipoic acid, selenium, and vitamin E on the livers of STZ-diabetic mice. İstanbul Journal of Pharmacy. 2023;53:199–210.
- Ben Hsouna A, Dhibi S, Dhifi W, Mnif W, Ben Nasr hmed, Hfaiedh N. Chemical composition and hepatoprotective effect of essential oil from Myrtus communis L. flowers against CCL 4 -induced acute hepatotoxicity in rats. RSC Adv. 2019;9:3777–87.
- Yamaguchi M, Kishi S. Prolonged administration of β-alanyl-L-histidinato zinc prevents bone loss in ovariectomized rats. Jpn J Pharmacol. 1993;63:203–7.
- Paradise WA, Vesper BJ, Goel A, Waltonen JD, Altman KW, Haines GK et al. Nitric oxide: Perspectives and emerging studies of a well known cytotoxin. Int J Mol Sci. 2010;11:2715–45.
- Sokolovska J, Dekante A, Baumane L, Pahirko L, Valeinis J, Dislere K. et al. Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy. Biomed Rep. 2020;12:251–8.
- Bayrak B, Mahmarzayeva D, Türkyılmaz İ, Saçan Ö, Yanardağ R. The protective effects of S-methyl methionine sulfonium chloride on brain tissue damage in D-galactosamine-induced hepatotoxicity. Experimed. 2022;12:38–43.
- Paape MJ, Sinha YN. Nucleic acid and collagen content of mammary glands between 30 and 80 days of age in normal and ovariectomized rats and during pregnancy. J Dairy Sci. 1971;54:1068–74.
- Tas S, Tas B, Bassalat N, Jaradat N. In-vivo, hypoglycemic, hypolipidemic and oxidative stress inhibitory activities of Myrtus communis L. fruits hydroalcoholic extract in normoglycemic and streptozotocin-induced diabetic rats. Biomed Res. 2018;29:2727–34.
- Magaji UF, Miftari S, Saçan Ö, Yanardağ R. Effect of antiepileptic drug sodium valproate on stomach tissue glycoproteins: The protective role of Moringa extract. Arch Epilepsy. 2023;29:41–5.
- Sacan O, Turkyilmaz IB, Bayrak BB, Mutlu O, Akev N, Yanardag R. Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats. BioMetals. 2016;29:239–48.
- Turkyilmaz IB, Altas N, Arisan I, Yanardag R. Effect of vitamin B-6 on brain damage in valproic acid induced toxicity. J Biochem Mol Toxicol. 2021;35:e22855.
- Ertik O, Sener G, Yanardag R. The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes. J Biochem Mol Toxicol. 2023;37.
- Niki E, Nakano M. Estrogens as antioxidants. Methods Enzymol. 1990;186:330–3.
- Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó F V, Viña J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med. 2003;34:546–52.