Identification of major phenolic compounds of Aloe vera and its protective effect on ovaries under oxidative stress in diabetic rats
Yıl 2023,
Cilt: 27 Sayı: 2, 652 - 664, 27.06.2025
Serdal Kurt
,
Uğur Şeker
,
Murat Onur Yazlık
,
Engin Er
Muhammed Mesud Hürkul
,
Sevda Söker
Öz
The study investigated the major phenolic compounds of Aloe vera leaf (AVL) by the high-performance
liquid chromatography (HPLC) method, and its protective effect on ovaries under oxidative stress of streptozotocin-
induced diabetic rats. The study was conducted on control (untreated healthy rats; C), diabetes (untreated diabetic rats;
D) and diabetes+A. vera treatment (diabetic rats treated with A. vera; D+A) groups. D+A group was given an ethanolic
extract of A. vera (300 mg/kg) for 14 days. Major phenolic compounds of AVL were chlorogenic acid and rutin. alanine
transaminase (ALT) and aspartate aminotransferase (AST) levels increased in D group compared to others groups
(P<0.01). Alkaline phosphatase (ALP) and albumin levels were lower and higher in the C group than in other groups,
respectively (P<0.01). In the D group compared to other groups, oxidative stress index (OSI) and total oxidant status
levels increased, while total antioxidant status level decreased in both ovarian tissues and blood (P<0.01). Preantral and
antral follicle counts decreased in the D group according to other groups (P<0.01) and atretic follicle count increased
(P<0.05). Proliferating cell nuclear antigen (PCNA) expression level (P<0.01), and B-cell lymphoma-2-associated-X-
protein (Bax; P<0.01) and tumor necrosis factor-alpha (TNF-α) expression levels (P<0.05) decreased and increased in
group D according to other groups, respectively. In conclusion, treatment with AVL decreased OSI, improved follicular
dynamics, and restored Bax, TNF-α and PCNA expression in diabetic rats.
Kaynakça
- Mohamed EAK. Anti-diabetic, antihypercholestermic and antioxidativeeffect of Aloe vera gel extract in
alloxaninduceddiabeticrats. Aust J Basic ApplSci. 2011;5: 1321-1327.
- Shima H, Naeem E, Hassan M, Hossein N. Aloe vera gel protects ovarian structure in diabetic rat. AEJTS. 2011;3(3):
197-203.
- Rosenbaum D, Haber RS, Dunaif A. Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4
glucose transporters in adipocytes. Am J Physiol Endocrinol Metab. 1993;264: E197-E202.
https://doi.org/10.1152/ajpendo.1993.264.2.E197
- Nayki U, Onk D, Balci G, Nayki C, Onk A,Gunay M. The effects of diabetes mellitus on ovarian injury and reserve: an
experimental study. Gynecol Obstet Invest. 2016;81: 424-429. https://doi.org/10.1159/000442287
- Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reproductive biology and
endocrinology. 2005; 3(1): 1-21.
- Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxid Med Cell Long.
2027;2017: 1-14. https://doi.org/10.1155/2017/4371714
- Sen S, Chakraborty R, Sridhar C, Reddy Y, De B. Free radicals, antioxidants, diseases and phytomedicines: current
status and future prospect. International Journal of Pharmaceutical Sciences and Re-search. 2010;3 (1) : 91-100
- Zhong, R.Z., Zhou, & D.W. Oxidative stress and role of natural plant derived antioxidants in animal reproduction. J
Integr Agric. 2013;12: 1826-1838. https://doi.org/10.1016/S2095-3119(13)60412-8
- Luximon-Ramma, A., Bahorun, T., Soobrattee, MA., &Aruoma, OI. Antioxidant activities of phenolic,
proanthocyanidin, and flavonoid components in extracts of Cassia fistula. J Agric Food Chem. 2002;50: 5042-5047.
https://doi.org/10.1021/jf0201172
- Kurt S, Koca RH, Hürkul MM, Seker U, Köroğlu A. The antioxidant effect of Michauxia campanuloides on rat
ovaries. J Hellenic Vet Med Soci. 2021;72(3): 3163-3170. https://doi.org/10.12681/jhvms.28510
- Rajasekaran S, Sivagnanam K, Subramanian S. Antioxidant effect of Aloe vera gel extract in streptozotocin-induced
diabetes in rats. Pharmacol Rep. 2005;57: 90-96.
- Anilakumar KR, Sudarshanakrishna KR, Chandramohan G, Ilaiyaraja N, Khanum F, Bawa AS. Effect of Aloe vera
gel extract on antioxidant enzymes and azoxymethane-induced oxidative stress in rats. Indian Journal of Experimental
Biology. 2010;48: 837-842.
- Manvitha K, Bidya B. Aloe vera: a wonder plant its history, cultivation and medicinal uses. J Pharmacogn
Phytochem 2014;2: 85-88.
- Eshun K, He Q. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries—a
review. Critical reviews in food science and nutrition. 2004;44(2): 91-96. https://doi.org/10.1080/10408690490424694
- Cristiano G, Murillo-Amador B, De Lucia B. Propagation techniques and agronomic requirements for the cultivation
of Barbados Aloe (Aloe vera (L.) Burm. F.) - a review. Front Plant Sci. 2016;7: 1410.
https://doi.org/10.3389/fpls.2016.01410
- Tan K. Aloe vera (L.) Burm.f. In: Davis PH (Ed.). Flora of Turkey and the East Aegean Islands. Edinburgh
UniversityPress, Edinburgh, 1984;8: 355-356.
- Maan AA, Nazir A, Khan MKI, Ahmad T, Zia R, Murid M, Abrar M. The therapeutic properties and applications of
Aloe vera: A review J Herb Med. 2018;12: 1-10https://doi.org/10.1016/j.hermed.2018.01.002
- Majumder R, Das CK, Mandal M. Lead bioactive compounds of Aloe vera as potential anticancer agent. Pharmacol
Res 2019;148: 104416. https://doi.org/10.1016/j.phrs.2019.104416
- Kumar, S. and Yadav, J.P. Ethnobotanical and pharmacological properties of Aloe vera: a review. J Med Plant Res.
2014;8: 1387-1398.
- Manjunath K, BhanuPrakash G, Subash KR, Tadvi NA, Manikanta M, UmamaheswaraRao K. Effect of Aloe vera leaf
extract on blood glucose levels in alloxan induced diabetic rats. Natl J Physiol Pharm. 2016;6: 471-474.
https://doi.org/10.5455/njppp.2016.6.0718613072016
- Haritha K, Ramesh B, Saralakumari D. Effect of Aloe vera gel on antioxidant enzymes in streptozotocin-induced
cataractogenesis in male and female Wistar rats. Journal of Acute Medicine. 2014;4: 38-44.
https://doi.org/10.1016/j.jacme.2014.01.005
- Park MK, Park JH, Kim NY, Shin YG, Choi YS, Lee JG, Lee SK. Analysis of 13 phenolic compounds in Aloe species
by high performance liquid chromatography. Phytochemical Analysis: Int J Plant Chem Biochem Technol. 1998;9: 186-
191. https://doi.org/10.1002/(SICI)1099-1565(199807/08)9:4%3c186::AID-PCA406%3e3.0.CO;2-%23
- International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for
Human Use. Validation of Analytical Procedures: Text and Methodology Q2 (R1), 2005; 1-13.
- Chabrolle C, JeanPierre E, Tosca L, Ramé C, Dupont J. Effects of high levels of glucose on the steroidogenesis and
the expression of adiponectin receptors in rat ovarian cells. Reproductive Biology and Endocrinology 2008; 6(1): 1-14.
https://doi.org/10.1186/1477-7827-6-11
- Ghanbari E, Nejati V, Khazaei M. Improvement in serum biochemical alterations and oxidative stress of liver and
pancreas following use of royal jelly in streptozotocin-induced diabetic rats. Cell Journal (Yakhteh) 2016;18(3): 362.
https://doi.org/10.22074/cellj.2016.4564
- Lalier L, Cartron PF, Juin P, Nedelkina S, Manon S, Bechinger B, Vallette FM. Bax activation and mitochondrial
insertion during apoptosis. Apoptosis 2007;12: 887-896. https://doi.org/10.1007/s10495-007-0749-1
- Annibaldi A, Meier P. Checkpoints in TNF-induced cell death: implications in inflammation and cancer. Trends in
molecular medicine 2018;24(1): 49-65. https://doi.org/10.1016/j.molmed.2017.11.002
- Strzalka W, Ziemienowicz A. Proliferating cell nuclear antigen (PCNA): a keyfactor in DNA replication and cell
cycle regulation. Ann Bot. 2011;107: 1127-1140. https://doi.org/10.1093/aob/mcq243
- TomĂĄnek M, Chronowska E. Immunohistochemical localization of proliferating cell nuclear antigen (PCNA) in
the pig ovary. Folia Histochem Cyto. 2006;44: 269-274.
- Can B, Atilgan R, Pala S, Kuloğlu T, Kiray S, Ilhan N. Examination of the effect of ovarian radiation injury induced
by hysterosalpingography on ovarian proliferating cell nuclear antigen and the radioprotective effect of amifostine: an
experimental study. Drug design, development and therapy. 2018;12: 1491.https://doi.org/10.2147/DDDT.S156757
- Sugino N. Reactive oxygen species in ovarian physiology. Reprod Med Biol. 2005;4: 31-44.
https://doi.org/10.1111/j.1447-0578.2005.00086.x
- Rajaei S, Alihemmati A, Abedelahi A. Antioxidant effect of genistein on ovarian tissue morphology, oxidant and
antioxidant activity in rats with induced polycystic ovary syndrome. Int J Rep Biomed. 2019;17: 1-12.
https://doi.org/10.18502/ijrm.v17i1.3816
- Pokorný J. Are natural antioxidants better–and safer–than synthetic antioxidants?.European journal of lipid science
and technology. 2007; 109(6): 629-642.https://doi.org/10.1002/ejlt.200700064
- Asif M. Chemistry and antioxidant activity of plants containing some phenolic compounds. Chemistry international.
215;1(1): 35-52.
- Soleymanı MM, Nourafshan A, Hamta A, Moumenı HR, Abnousi MH, Mahmoudi M, Anvari M, Hazaveh M.
Effects of vitamin E on ovarian tissue of rats following treatment with p-nonylphenol. A Stereological Study. Iran J
Reprod Med. 2010;8, 1-9.
- Majd NE, Azizian H, Tabandeh MR, Shahriari A. Effect of Abelmoschus esculentus powder on ovarian histology,
expression of apoptotic genes and oxidative stress in diabetic rats fed with high fat diet. IJPR. 2019;18: 369-382.
- Nna VU, Usman UZ, Ofutet EO, Owu DU. Quercetin exerts preventive, ameliorative and prophylactic effects on
cadmium chloride-induced oxidative stress in the uterus and ovaries of female Wistar rats. Food Chem Toxicol. 2017;102:
143-155.https://doi.org/10.1016/j.fct.2017.02.010
- Shathili AM, Brown HM, Everest-Dass AV, Tan TC, Parker LM, Thompson JG, Packer NH. The effect of
streptozotocin-induced hyperglycemia on N-and O-linked protein glycosylation in mouse ovary. Glycobiology. 2018;28:
832-840.https://doi.org/10.1093/glycob/cwy075
- Drimal J, Knezl V, Navarova J, Nedelcevova J, Paulovicova E, Sotnikova R, Drimal D. Role of inflammatory
cytokines and chemoattractants in the rat model of streptozotocin-induced diabetic heart failure. Endocrine
regulations. 2008;42(4): 129-135.
- shkar F, Rezaei S, Salahshoornezhad S, Vahid F, Gholamalizadeh M, Dahka SM, Doaei S. The Role of medicinal
herbs in treatment of insulin resistance in patients with Polycystic Ovary Syndrome: A literature review. Biomolecular
concepts 2019;11(1): 57-75.
- Rajasekaran S, Sivagnanam K, Ravi K, Subramanian S. Hypoglycemic effect of Aloe vera gel on streptozotocin-
induced diabetes in experimental rats. Journal of Medicinal food. 2004;7(1): 61-66.
https://doi.org/10.1089/109662004322984725
- Rajasekaran S, Sivagnanam K, Subramanian S. Modulatory effects of Aloe vera leaf gel extract on oxidative stress in
rats treated with streptozotocin. Journal of pharmacy and pharmacology 2005;57(2): 241-246.
https://doi.org/10.1211/0022357055416
- Sakr SA, Abdel-Aziz KK, El-kott AF, Khalifa HS. Ameliorative effect of olive leaves extract on hepatotoxicity and
oxidative stress in streptozotocin-induced diabetic rats. JBAR. 2016;2, 549-560.
https://doi.org/10.21608/JBAAR.2016.108933
- Feldman AT, Wolfe D. (2014). Tissue processing and hematoxylin and eosinstaining. In Histopathology. New York:
Humana Press; 2014. p.31-43. https://doi.org/10.1007/978-1-4939-1050-2_3
- Seker U, Eşki F, Kurt S. Investigation of the Distribution and Expression Level of Pro and Anti-Apoptotic Bax and
Bcl-2 in Ovarian Follicles at DifferentDevelopmentalStages. Harran Üniversitesi Tıp Fakültesi Dergisi. 2021; 18: 424-428.
https://doi.org/10.35440/hutfd.995512
- Eşki F, Kurt S, Demir PA. Effect of different estrus synchronization protocols on estrus and pregnancy rates,
oxidative stress and some biochemical parameters in Hair goats. Small Ruminant Research. 2021;198: 1-6.
https://doi.org/10.1016/j.smallrumres.2021.106348
- Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle
transition in rat ovaries. Mol Cell Endocrinol. 2002;188: 65-73. https://doi.org/10.1016/S0303-7207(01)00746-8
- Muskhelishvili L, Wingard SK, Latendresse JR. Proliferating cell nuclear antigen—a marker for ovarian follicle
counts. Toxicol Pathol 2005;33: 365-368. https://doi.org/10.1080/01926230590930164
Yıl 2023,
Cilt: 27 Sayı: 2, 652 - 664, 27.06.2025
Serdal Kurt
,
Uğur Şeker
,
Murat Onur Yazlık
,
Engin Er
Muhammed Mesud Hürkul
,
Sevda Söker
Kaynakça
- Mohamed EAK. Anti-diabetic, antihypercholestermic and antioxidativeeffect of Aloe vera gel extract in
alloxaninduceddiabeticrats. Aust J Basic ApplSci. 2011;5: 1321-1327.
- Shima H, Naeem E, Hassan M, Hossein N. Aloe vera gel protects ovarian structure in diabetic rat. AEJTS. 2011;3(3):
197-203.
- Rosenbaum D, Haber RS, Dunaif A. Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4
glucose transporters in adipocytes. Am J Physiol Endocrinol Metab. 1993;264: E197-E202.
https://doi.org/10.1152/ajpendo.1993.264.2.E197
- Nayki U, Onk D, Balci G, Nayki C, Onk A,Gunay M. The effects of diabetes mellitus on ovarian injury and reserve: an
experimental study. Gynecol Obstet Invest. 2016;81: 424-429. https://doi.org/10.1159/000442287
- Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reproductive biology and
endocrinology. 2005; 3(1): 1-21.
- Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxid Med Cell Long.
2027;2017: 1-14. https://doi.org/10.1155/2017/4371714
- Sen S, Chakraborty R, Sridhar C, Reddy Y, De B. Free radicals, antioxidants, diseases and phytomedicines: current
status and future prospect. International Journal of Pharmaceutical Sciences and Re-search. 2010;3 (1) : 91-100
- Zhong, R.Z., Zhou, & D.W. Oxidative stress and role of natural plant derived antioxidants in animal reproduction. J
Integr Agric. 2013;12: 1826-1838. https://doi.org/10.1016/S2095-3119(13)60412-8
- Luximon-Ramma, A., Bahorun, T., Soobrattee, MA., &Aruoma, OI. Antioxidant activities of phenolic,
proanthocyanidin, and flavonoid components in extracts of Cassia fistula. J Agric Food Chem. 2002;50: 5042-5047.
https://doi.org/10.1021/jf0201172
- Kurt S, Koca RH, Hürkul MM, Seker U, Köroğlu A. The antioxidant effect of Michauxia campanuloides on rat
ovaries. J Hellenic Vet Med Soci. 2021;72(3): 3163-3170. https://doi.org/10.12681/jhvms.28510
- Rajasekaran S, Sivagnanam K, Subramanian S. Antioxidant effect of Aloe vera gel extract in streptozotocin-induced
diabetes in rats. Pharmacol Rep. 2005;57: 90-96.
- Anilakumar KR, Sudarshanakrishna KR, Chandramohan G, Ilaiyaraja N, Khanum F, Bawa AS. Effect of Aloe vera
gel extract on antioxidant enzymes and azoxymethane-induced oxidative stress in rats. Indian Journal of Experimental
Biology. 2010;48: 837-842.
- Manvitha K, Bidya B. Aloe vera: a wonder plant its history, cultivation and medicinal uses. J Pharmacogn
Phytochem 2014;2: 85-88.
- Eshun K, He Q. Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries—a
review. Critical reviews in food science and nutrition. 2004;44(2): 91-96. https://doi.org/10.1080/10408690490424694
- Cristiano G, Murillo-Amador B, De Lucia B. Propagation techniques and agronomic requirements for the cultivation
of Barbados Aloe (Aloe vera (L.) Burm. F.) - a review. Front Plant Sci. 2016;7: 1410.
https://doi.org/10.3389/fpls.2016.01410
- Tan K. Aloe vera (L.) Burm.f. In: Davis PH (Ed.). Flora of Turkey and the East Aegean Islands. Edinburgh
UniversityPress, Edinburgh, 1984;8: 355-356.
- Maan AA, Nazir A, Khan MKI, Ahmad T, Zia R, Murid M, Abrar M. The therapeutic properties and applications of
Aloe vera: A review J Herb Med. 2018;12: 1-10https://doi.org/10.1016/j.hermed.2018.01.002
- Majumder R, Das CK, Mandal M. Lead bioactive compounds of Aloe vera as potential anticancer agent. Pharmacol
Res 2019;148: 104416. https://doi.org/10.1016/j.phrs.2019.104416
- Kumar, S. and Yadav, J.P. Ethnobotanical and pharmacological properties of Aloe vera: a review. J Med Plant Res.
2014;8: 1387-1398.
- Manjunath K, BhanuPrakash G, Subash KR, Tadvi NA, Manikanta M, UmamaheswaraRao K. Effect of Aloe vera leaf
extract on blood glucose levels in alloxan induced diabetic rats. Natl J Physiol Pharm. 2016;6: 471-474.
https://doi.org/10.5455/njppp.2016.6.0718613072016
- Haritha K, Ramesh B, Saralakumari D. Effect of Aloe vera gel on antioxidant enzymes in streptozotocin-induced
cataractogenesis in male and female Wistar rats. Journal of Acute Medicine. 2014;4: 38-44.
https://doi.org/10.1016/j.jacme.2014.01.005
- Park MK, Park JH, Kim NY, Shin YG, Choi YS, Lee JG, Lee SK. Analysis of 13 phenolic compounds in Aloe species
by high performance liquid chromatography. Phytochemical Analysis: Int J Plant Chem Biochem Technol. 1998;9: 186-
191. https://doi.org/10.1002/(SICI)1099-1565(199807/08)9:4%3c186::AID-PCA406%3e3.0.CO;2-%23
- International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for
Human Use. Validation of Analytical Procedures: Text and Methodology Q2 (R1), 2005; 1-13.
- Chabrolle C, JeanPierre E, Tosca L, Ramé C, Dupont J. Effects of high levels of glucose on the steroidogenesis and
the expression of adiponectin receptors in rat ovarian cells. Reproductive Biology and Endocrinology 2008; 6(1): 1-14.
https://doi.org/10.1186/1477-7827-6-11
- Ghanbari E, Nejati V, Khazaei M. Improvement in serum biochemical alterations and oxidative stress of liver and
pancreas following use of royal jelly in streptozotocin-induced diabetic rats. Cell Journal (Yakhteh) 2016;18(3): 362.
https://doi.org/10.22074/cellj.2016.4564
- Lalier L, Cartron PF, Juin P, Nedelkina S, Manon S, Bechinger B, Vallette FM. Bax activation and mitochondrial
insertion during apoptosis. Apoptosis 2007;12: 887-896. https://doi.org/10.1007/s10495-007-0749-1
- Annibaldi A, Meier P. Checkpoints in TNF-induced cell death: implications in inflammation and cancer. Trends in
molecular medicine 2018;24(1): 49-65. https://doi.org/10.1016/j.molmed.2017.11.002
- Strzalka W, Ziemienowicz A. Proliferating cell nuclear antigen (PCNA): a keyfactor in DNA replication and cell
cycle regulation. Ann Bot. 2011;107: 1127-1140. https://doi.org/10.1093/aob/mcq243
- TomĂĄnek M, Chronowska E. Immunohistochemical localization of proliferating cell nuclear antigen (PCNA) in
the pig ovary. Folia Histochem Cyto. 2006;44: 269-274.
- Can B, Atilgan R, Pala S, Kuloğlu T, Kiray S, Ilhan N. Examination of the effect of ovarian radiation injury induced
by hysterosalpingography on ovarian proliferating cell nuclear antigen and the radioprotective effect of amifostine: an
experimental study. Drug design, development and therapy. 2018;12: 1491.https://doi.org/10.2147/DDDT.S156757
- Sugino N. Reactive oxygen species in ovarian physiology. Reprod Med Biol. 2005;4: 31-44.
https://doi.org/10.1111/j.1447-0578.2005.00086.x
- Rajaei S, Alihemmati A, Abedelahi A. Antioxidant effect of genistein on ovarian tissue morphology, oxidant and
antioxidant activity in rats with induced polycystic ovary syndrome. Int J Rep Biomed. 2019;17: 1-12.
https://doi.org/10.18502/ijrm.v17i1.3816
- Pokorný J. Are natural antioxidants better–and safer–than synthetic antioxidants?.European journal of lipid science
and technology. 2007; 109(6): 629-642.https://doi.org/10.1002/ejlt.200700064
- Asif M. Chemistry and antioxidant activity of plants containing some phenolic compounds. Chemistry international.
215;1(1): 35-52.
- Soleymanı MM, Nourafshan A, Hamta A, Moumenı HR, Abnousi MH, Mahmoudi M, Anvari M, Hazaveh M.
Effects of vitamin E on ovarian tissue of rats following treatment with p-nonylphenol. A Stereological Study. Iran J
Reprod Med. 2010;8, 1-9.
- Majd NE, Azizian H, Tabandeh MR, Shahriari A. Effect of Abelmoschus esculentus powder on ovarian histology,
expression of apoptotic genes and oxidative stress in diabetic rats fed with high fat diet. IJPR. 2019;18: 369-382.
- Nna VU, Usman UZ, Ofutet EO, Owu DU. Quercetin exerts preventive, ameliorative and prophylactic effects on
cadmium chloride-induced oxidative stress in the uterus and ovaries of female Wistar rats. Food Chem Toxicol. 2017;102:
143-155.https://doi.org/10.1016/j.fct.2017.02.010
- Shathili AM, Brown HM, Everest-Dass AV, Tan TC, Parker LM, Thompson JG, Packer NH. The effect of
streptozotocin-induced hyperglycemia on N-and O-linked protein glycosylation in mouse ovary. Glycobiology. 2018;28:
832-840.https://doi.org/10.1093/glycob/cwy075
- Drimal J, Knezl V, Navarova J, Nedelcevova J, Paulovicova E, Sotnikova R, Drimal D. Role of inflammatory
cytokines and chemoattractants in the rat model of streptozotocin-induced diabetic heart failure. Endocrine
regulations. 2008;42(4): 129-135.
- shkar F, Rezaei S, Salahshoornezhad S, Vahid F, Gholamalizadeh M, Dahka SM, Doaei S. The Role of medicinal
herbs in treatment of insulin resistance in patients with Polycystic Ovary Syndrome: A literature review. Biomolecular
concepts 2019;11(1): 57-75.
- Rajasekaran S, Sivagnanam K, Ravi K, Subramanian S. Hypoglycemic effect of Aloe vera gel on streptozotocin-
induced diabetes in experimental rats. Journal of Medicinal food. 2004;7(1): 61-66.
https://doi.org/10.1089/109662004322984725
- Rajasekaran S, Sivagnanam K, Subramanian S. Modulatory effects of Aloe vera leaf gel extract on oxidative stress in
rats treated with streptozotocin. Journal of pharmacy and pharmacology 2005;57(2): 241-246.
https://doi.org/10.1211/0022357055416
- Sakr SA, Abdel-Aziz KK, El-kott AF, Khalifa HS. Ameliorative effect of olive leaves extract on hepatotoxicity and
oxidative stress in streptozotocin-induced diabetic rats. JBAR. 2016;2, 549-560.
https://doi.org/10.21608/JBAAR.2016.108933
- Feldman AT, Wolfe D. (2014). Tissue processing and hematoxylin and eosinstaining. In Histopathology. New York:
Humana Press; 2014. p.31-43. https://doi.org/10.1007/978-1-4939-1050-2_3
- Seker U, Eşki F, Kurt S. Investigation of the Distribution and Expression Level of Pro and Anti-Apoptotic Bax and
Bcl-2 in Ovarian Follicles at DifferentDevelopmentalStages. Harran Üniversitesi Tıp Fakültesi Dergisi. 2021; 18: 424-428.
https://doi.org/10.35440/hutfd.995512
- Eşki F, Kurt S, Demir PA. Effect of different estrus synchronization protocols on estrus and pregnancy rates,
oxidative stress and some biochemical parameters in Hair goats. Small Ruminant Research. 2021;198: 1-6.
https://doi.org/10.1016/j.smallrumres.2021.106348
- Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle
transition in rat ovaries. Mol Cell Endocrinol. 2002;188: 65-73. https://doi.org/10.1016/S0303-7207(01)00746-8
- Muskhelishvili L, Wingard SK, Latendresse JR. Proliferating cell nuclear antigen—a marker for ovarian follicle
counts. Toxicol Pathol 2005;33: 365-368. https://doi.org/10.1080/01926230590930164