The Role of Alpha Lipoic Acid and Olive Oil on Metabolic Syndrome Associated with Letrozole-induced Polycystic Ovarian Syndrome

INTRODUCTION

A prevalent reproductive endocrine disorder called polycystic ovarian syndrome (PCOS) affects 5–10% of females who are of reproductive age. Over 116 million women globally, according to estimates from the World Health Organization (WHO), have PCOS. Hyperandrogenism, anovulatory infertility, irregular menstruation, and metabolic abnormalities such obesity, insulin resistance (IR), hyperinsulinemia, dyslipidemia, and glucometabolic diseases are some of its hallmarks. The main PCOS treatments currently used are lifestyle modifications and drugs that help with weight management, ovulation induction, IR reduction, menstrual cycle regulation, and serum androgen levels.

One of the symptoms of PCOS is a drop in Sex Hormone Binding Globin (SHBG) levels, which is connected to insulin resistance and hyperandrogenism. Estradiol, Progesterone, Testosterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and Insulin are examples of selective reproductive hormones that should be studied. The ovarian hyperstimulation syndrome (OHSS), gastrointestinal issues, irregular glucose and lipid metabolism, mental disturbance, hair loss, vision loss, and allergic dermatitis are only a few of the side effects that these medications may cause. They may also not significantly help Insulin resistance (IR) and metabolic abnormalities when given alone, necessitating their combination with additional therapeutics.

The natural antioxidant alpha-lipoic acid (ALA), which is produced by both plants and animals, is known to act as a catalyst in the oxidative decarboxylation of pyruvate and –ketoglutarate. ALA lowers insulin resistance and oxidative stress in women with polycystic ovary syndrome (PCOS). The lipophilic natural antioxidant alpha-lipoic acid (ALA) serves as a crucial cofactor for mitochondrial enzymes. Particularly in lab-grown liver, lung, and kidney cell cultures, it boosts the potency of other antioxidants like glutathione by 30 to 70%. The complex ALA-DHLA gets involved in the repair of DNA, lipids, and proteins that have been oxidized-damaged. ALA has attracted interest in recent years for the treatment of neurological and liver illnesses. It has been used in people with type-2 diabetes to enhance glucose control and to alleviate symptoms of diabetic neuropathy.

Olive oil considerably reduced TC less than oils high in omega-3s, according to research by Ghobadi et al. (2019). On the other hand, PCOS women's inflammatory state is known to be influenced by the ratio of n-6 to n-3 fatty acids.

Despite the complexity of PCOS' pathophysiology, there is mounting evidence that oxidative stress (OS) plays a role in the disease's etiology. Numerous studies have demonstrated that PCOS patients have elevated levels of OS indicators, which may increase their chance of developing long-term problems such type 2 diabetes (T2DM) and endometrial cancer. In order to provide a useful reference for the clinical treatment of PCOS as well as for the research and development of new drugs, this study investigates the use of antioxidants as a therapeutic.

1.1 Statement of Problem

Obesity, insulin resistance, hyperinsulinemia, hypertension, and dyslipidemia are all cardiometabolic risk factors that are included in the metabolic syndrome associated with PCOS. There is growing proof that oxidative stress (OS) contributes to the pathophysiology of this condition. A number of human metabolic syndrome, including diabetes, hypertension, and aging, are thought to be largely influenced by oxidative stress, but there is none to harness letrozole-induced PCOS. Numerous studies have demonstrated that PCOS individuals have higher levels of OS markers. Therefore, there is need to evaluate the role of ALA and olive oil as management options in the metabolic syndrome associated with letrozole-induced PCOS rats compared to clomiphene citrate and metformin that have toxicological effects in the treatment of PCOS.

1.2 Justification of Study

Numerous studies on PCOS patients have shown that antioxidants can not only enhance the ovarian environment, encourage follicular maturation, and increase oocyte quantities, but can also control lipid and glucose metabolism as well as vascular endothelial cell function in PCOS patients. This lowers adiposity and lowers the frequency of chronic complications to ensure that patients can benefit long-term. ALA may be utilized to stop premature fetal membrane rupture brought on by inflammation and diabetic embryopathy. ALA lowers insulin resistance and oxidative stress as well as olive oil which reduce TC in women with polycystic ovary syndrome (PCOS). Therefore there is need to evaluate the ameliorative effects of ALA on metabolic syndrome such as hyperinsulinemia, dyslipidemia and hyperglycemia associated with PCOS in rat model.

1.3 Aim of Study

The aim of this study is to determine the ameliorative effects of ALA and olive oil as a management option in the metabolic syndrome associated with letrozole-induced PCOS female rats.

1.4 Specific Objectives of Study

The specific objectives of this study are as follows:

1. To induce PCOS using letrozole on female Wistar rats and monitor the oestrous cycle,
2. To evaluate the ameliorative effects of ALA and olive oil as management options of PCOS.
3. To determine the serum lipid profile of PCOS rats,
4. To evaluate the associated metabolic disturbance associated with PCOS such as hyperglycemia and increased body weight and hyperinsulinemia.