EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL

OBJECTIVE: To evaluate the effect of canagliflozin and metformin on the estrous cycle and hormonal derangement of letrozole induced polycystic ovarian syndrome (PCOS) in Sprague Dawly rats. METHODS:  Thirty six female adult non-pregnant Sprague Dawly rats were divided into six groups and all, exc...

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Main Authors: Akfish Zaheer, Rabab Miraj, Nada Azam, Amir Hassan, Sadia Chiragh
Format: Article
Language:English
Published: Khyber Medical University 2021-06-01
Series:Khyber Medical University Journal
Subjects:
Online Access:https://www.kmuj.kmu.edu.pk/article/view/20602
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author Akfish Zaheer
Rabab Miraj
Nada Azam
Amir Hassan
Sadia Chiragh
author_facet Akfish Zaheer
Rabab Miraj
Nada Azam
Amir Hassan
Sadia Chiragh
author_sort Akfish Zaheer
collection DOAJ
description OBJECTIVE: To evaluate the effect of canagliflozin and metformin on the estrous cycle and hormonal derangement of letrozole induced polycystic ovarian syndrome (PCOS) in Sprague Dawly rats. METHODS:  Thirty six female adult non-pregnant Sprague Dawly rats were divided into six groups and all, except normal control (A), were treated with letrozole 1mg/kg daily for 21 days. Treatment was started to all rats except normal control (group-A) and disease control (group-B). Canagliflozin 10 mg/kg, metformin 100 mg/kg and their combinations in high and low doses were given daily to rats of groups-C (canagliflozin-alone), group-D (metformin-alone), group-E (high dose combination) and group-F (low dose combination) respectively. Vaginal smears were taken daily, to observe the estrous cycle, till the 48th day of study. Blood samples were collected on the 22nd and 48th day for hormonal assay. RESULTS: Significant increase in serum estradiol levels (ηg/dl) [group-A=46.53±9.40, group-B=18.75±2.48, group-C=23.00±10.15, group-D=37.41±8.54, group-E=57.58±12.88, group-F=41.93±10.32] and Follicle Stimulating Hormone levels (IU) [group-A=22.90±5.98, group-B=9.30±2.88, group-C=25.73±6.70, group-D=17.60±4.89, group-E=27.36±4.12, group-F=16.11±3.56] and decrease in testosterone levels (ηg/dl) [group-A=4.48±1.21, group-B=10.12±2.90, group-C=2.85±1.00, group-D=4.41±2.30, group-E=2.50±1.28, group-F=4.15±0.79] and Luteinizing Hormone levels(ηg/dl) [group-A=24.55±7.07, group-B=31.25±12.88, group-C=7.71±2.89, group-D=11.43±7.17, group-E=6.98±2.28, group-F=15.86±16.35]. Number of estrous cycles were significantly less in group-B (3-4 cycles/rat). Group-E (10-11 cycles/rat) resulted in significantly high estrous cycles number as compared to group-C (8-9 cycles/rat), group-D and group-F (7-8 cycles/rat). CONCLUSION: Canagliflozin is effective alone and augment the effect of metformin for the regularization of estrous cycles and reversal of hormonal derangements in a rat model of PCOS.
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spelling doaj.art-69b2ae98aeb14a82a44cd9a251974c422023-06-09T19:18:39ZengKhyber Medical UniversityKhyber Medical University Journal2305-26432305-26512021-06-01132768110.35845/kmuj.2021.206021382EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODELAkfish Zaheer0Rabab Miraj1Nada Azam2Amir Hassan3Sadia Chiragh4Department of Pharmacology, Post Graduate Medical Institute, Lahore, Pakistan currently working in Department of Pharmacology, University of Faisalabad, PakistanDepartment of Pharmacology, Post Graduate Medical Institute, Lahore, Pakistan currently working in Department of Pharmacology, Amna Anayat Medical College, Lahore, PakistanDepartment of Pharmacology, Post Graduate Medical Institute, Lahore, Pakistan currently working in Department of Pharmacology, Central Pak Medical College, Lahore, PakistanDepartment of Pharmacology, Post Graduate Medical Institute, Lahore, PakistanDepartment of Pharmacology, Post Graduate Medical Institute, Lahore, Pakistan currently working in Department of Pharmacology, Al Aleem Medical College, Lahore, PakistanOBJECTIVE: To evaluate the effect of canagliflozin and metformin on the estrous cycle and hormonal derangement of letrozole induced polycystic ovarian syndrome (PCOS) in Sprague Dawly rats. METHODS:  Thirty six female adult non-pregnant Sprague Dawly rats were divided into six groups and all, except normal control (A), were treated with letrozole 1mg/kg daily for 21 days. Treatment was started to all rats except normal control (group-A) and disease control (group-B). Canagliflozin 10 mg/kg, metformin 100 mg/kg and their combinations in high and low doses were given daily to rats of groups-C (canagliflozin-alone), group-D (metformin-alone), group-E (high dose combination) and group-F (low dose combination) respectively. Vaginal smears were taken daily, to observe the estrous cycle, till the 48th day of study. Blood samples were collected on the 22nd and 48th day for hormonal assay. RESULTS: Significant increase in serum estradiol levels (ηg/dl) [group-A=46.53±9.40, group-B=18.75±2.48, group-C=23.00±10.15, group-D=37.41±8.54, group-E=57.58±12.88, group-F=41.93±10.32] and Follicle Stimulating Hormone levels (IU) [group-A=22.90±5.98, group-B=9.30±2.88, group-C=25.73±6.70, group-D=17.60±4.89, group-E=27.36±4.12, group-F=16.11±3.56] and decrease in testosterone levels (ηg/dl) [group-A=4.48±1.21, group-B=10.12±2.90, group-C=2.85±1.00, group-D=4.41±2.30, group-E=2.50±1.28, group-F=4.15±0.79] and Luteinizing Hormone levels(ηg/dl) [group-A=24.55±7.07, group-B=31.25±12.88, group-C=7.71±2.89, group-D=11.43±7.17, group-E=6.98±2.28, group-F=15.86±16.35]. Number of estrous cycles were significantly less in group-B (3-4 cycles/rat). Group-E (10-11 cycles/rat) resulted in significantly high estrous cycles number as compared to group-C (8-9 cycles/rat), group-D and group-F (7-8 cycles/rat). CONCLUSION: Canagliflozin is effective alone and augment the effect of metformin for the regularization of estrous cycles and reversal of hormonal derangements in a rat model of PCOS.https://www.kmuj.kmu.edu.pk/article/view/20602estradiolestrogenestrous cyclefollicle stimulating hormoneletrozoleluteinizing hormonetestosteronecanagliflozinmetformin
spellingShingle Akfish Zaheer
Rabab Miraj
Nada Azam
Amir Hassan
Sadia Chiragh
EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
Khyber Medical University Journal
estradiol
estrogen
estrous cycle
follicle stimulating hormone
letrozole
luteinizing hormone
testosterone
canagliflozin
metformin
title EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
title_full EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
title_fullStr EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
title_full_unstemmed EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
title_short EFFECT OF CANAGLIFLOZIN ALONE AND IN COMBINATION WITH METFORMIN ON HORMONAL DERANGEMENTS AND ESTROUS CYCLE IN A POLYCYSTIC OVARY SYNDROME RAT MODEL
title_sort effect of canagliflozin alone and in combination with metformin on hormonal derangements and estrous cycle in a polycystic ovary syndrome rat model
topic estradiol
estrogen
estrous cycle
follicle stimulating hormone
letrozole
luteinizing hormone
testosterone
canagliflozin
metformin
url https://www.kmuj.kmu.edu.pk/article/view/20602
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