Combined Intranasal Insulin/Saxagliptin/Metformin Therapies Ameliorate the Effect of Combined Oral Contraceptive- (COC-) Induced Metabolic Syndrome (MetS) with a Major Target on Glucose Metabolism in Adult Female Wistar Rats.

Saheed Olanrewaju Afolabi,Olalekan Agede,Olufunke Olorundare,Joy Folahan,Vikas Roy

doi:10.1155/2021/9693171

Saheed Olanrewaju Afolabi, Olalekan Agede + Show 3 more

Open Access

https://doi.org/10.1155/2021/9693171

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Abstract

Objective To evaluate the effect of the chronic use of combined oral contraceptives (COCs: ethinyl estradiol and levonorgestrel) on the indices of metabolic syndrome in adult female Wistar rats and possible therapeutic management. Materials and Methods 64 female Wistar rats received either distilled water, norethindrone (NOR), COC, intranasal insulin (INI), metformin (MET), saxagliptin (SAX), INI+MET, and INI+SAX. After 8 weeks of exposure to COC, the animals were sorted into the therapeutic groups. Several parameters were assayed for, such as body weight changes, fasting blood glucose (FBG) level, insulin levels, inflammatory cytokines, and glycated hemoglobin (Hb1Ac). Results The levels of FBG, insulin, and Hb1Ac were increased consequent upon COC treatment. Treatment with INI+SAX and INI+MET reduced significantly the levels of FBG and Hb1Ac; in addition, the level of insulin was significantly increased in the INI+MET groups (p ≤ 0.05). Serum lipid profile analysis showed a statistical reduction in high-density lipoprotein (HDL) level; this reduction was also significantly reversed in the INI+SAX group. Reduced catalase activity observed in the COC group was reversed in the INI+MET group (p ≤ 0.05). A nonsignificant increase in the level of TNF-α as a result of COC treatment was reversed by INI and INI+MET treatment. Liver GLUT4 and G-6-phosphate levels were significantly increased by COC treatment, and this effect was reversed by INI+SAX in both assays, respectively (p ≤ 0.01). Conclusions The use of MET and SAX in combination with INI has been shown to reverse some indices of MetS. This study proposes a clinical phase to backup and ascertain these preclinical findings.

Highlights

Premenopausal women are active users of hormonal contraceptives
There was a significant increase in the fasting blood glucose level of the COC group (p ≤ 0:05); this alteration was reversed in the INI group (p ≤ 0:05) and the SAX group (p ≤ 0:01) (Figure 2(a))
The oral glucose tolerance test (OGTT) showed no significant effect across the treatment groups except for the initial spike in glucose level observed at the 0 min timepoint (Figure 2(b))

Summary

Introduction

Premenopausal women are active users of hormonal contraceptives. There has been an upsurge in this usage; scientific reports have estimated that over 150 million sexually active women subscribe to these pharmaceuticals globally [1,2,3]. Available formulations consisting of a synthetic estrogen and progestin constitute the globally recognized combined oral contraceptives (COCs) [4, 5]. In addition to its contraceptive effects, constant administration of COC is being explored as a therapeutic intervention against polycystic ovary syndrome (PCOS) and dysmenorrhea [6, 7]. Ethinyl estradiol (EE), synthesized from 17β-estradiol (E2), is the most used synthetic estrogen in COC [7, 12, 13]; it is an estrogen receptor agonist. EE is almost exclusively employed for the adjunctive role it plays in the COC, making it the most widely used

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