The benefits of hyperbaric oxygen therapy in PCOS model mice with insulin resistance

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Illustration by Alodokter

Polycystic Ovary Syndrome (PCOS), also known as Stein-Leventhal syndrome is a women’s health problem that often occurs at a young age even when still a teenager. This syndrome is characterized by the presence of oligomenorrhea or amenorrhoea, obesity, and various symptoms of hyperandrogenism. The hormonal condition of women with PCOS shows a chronic anovulatory condition with various causes that interact with each other. Insulin resistance is a common feature that occurs in 50-75% of obese people, and one of the manifestations that appear in people with PCOS. Insulin sensitivity decreases 35-50% in people with PCOS both in obese and non-obese people compared to normal women. About 35% of PCOS sufferers show impaired glucose tolerance, and 7-10% meet the type 2 DM criteria.

The condition of insulin resistance in PCOS causes hyperinsulinemia. Hyperinsulinemia stimulates ovarian theca cells to produce excess androgens in PCOS patients to bring about hyperandrogenemia. The condition of hyperinsulinemia and hyperandrogenemia decreases the production of sex hormone-binding globulin and IGF1BP in the liver so that the levels of androgen and IGF1 free hormones increase. Increased androgens are also due to the insulin-IGF1 complex reaction, which stimulates the theca cells to produce more androgens. The condition of hyperandrogenemia in PCOS results in the onset of symptoms of hirsutism as well as an unfavorable condition in the intra ovary that causes ovulation failure. Some studies find a strong relationship between androgens and miscarriages, namely through direct influence on oocytes, other evidence found hyperandrogenemia, along with increased levels of LH negatively affect the development of the endometrium. Androgens and their receptors are thought to have a more significant role in endometrial abnormalities in PCOS, which is found to be higher in endometrial PCOS, especially in the amenorrhoea group.

Hyperbaric oxygen therapy (TOHB) is a therapy for breathing someone breathing in 100% oxygen in a chamber with higher pressure than air pressure at sea level, which is 1 ATA. Although the exact mechanism of action is not widely known, the use of this therapy has been widely accepted. Initially, this therapy was intended to treat decompression sickness and arterial gas embolism, but now its use is developing in various other cases. Some things that are expected from TOHB are an increase in the production of antioxidant enzymes (SOD) due to the production of ROS at a certain level, and the use of ROS itself as a second messenger in the expected process. Hyperbaric oxygen therapy can improve insulin resistance in people with type DM, improve uterine receptivity in the endometrium.

The study used 20 female Wistar mice, and there were no dropout samples in this study. Wistar rat weights used in this study ranged from 100 to 120 grams. After the rats were grouped randomly into two groups, the normality test showed that body weight in the control group, and the treatment group was not normally distributed (p = 0.08; 0.36 each). There was no significant difference in mean body weight between the control and treatment groups (108.5 ± 8.83 grams vs. 109 ± 7.38 grams, p = 0.808). The IRS AR expression in the control group and the treatment group in this study were normally distributed (p = 0.313; 0.474 each). The average IRS score between the control group and the treatment group was significantly different (1.64 ± 1.38 vs. 0.8 ± 0.6, p = 0.025). Serum SOD levels in the control and treatment groups were normally distributed (p = 0.599; 0.114 each). The mean serum SOD level between the control group and the treatment group was significantly different (0.13 ± 0.03ng / ml vs 0.2 ± 0.06ng / mg, p = 0.011). In this study, we found that HBOT significantly reduced AR expression. Moreover, AR expression in PCOS is caused by an increase in serum androgen levels. In contrast, an increase in serum androgen levels due to hyperinsulinemia and hyperinsulinemia caused by IR.

Other studies showed that TOHB can increase insulin sensitivity in obese women with type 2 DM also found a decrease in HbA1c in non-obese women in type 2 DM. In this study, TOHB significantly increased SOD levels in SOPK model mice with insulin resistance. SOD is the first line of defense in antioxidant reactions to ROS. At low to moderate concentrations, ROS is involved in physiological roles, including defense against infectious agents and some cellular signaling systems. But when present excessively, ROS can damage DNA, cellular lipids, and proteins, disrupting their normal functioning. TOHB triggers and increases antioxidant enzymes as a defense mechanism against OS. Increased tissue oxygenation can activate other endogenous factors that prevent the harmful effects of the disease itself. There is concern that TOHB can increase oxidative stress through ROS production. However, this treatment is considered safe because of the increased free radical activity. In the long-term, TOHB can reduce oxidative stress by reducing lipid peroxidation and by increasing the activity of antioxidant enzymes.

It is recommended that TOHB can reduce lipid peroxidation by inhibiting neutrophil adhesion. However, in this current study, short-term TOHB administration has shown a significant increase in serum SOD levels. For safety reasons, the TOHB pressure must not exceed 3 atm and must not exceed 90 minutes per therapy session. If these safety guidelines are not followed, free radicals can accumulate and can cause oxygen poisoning in the central nervous system and the lungs. The conclusion of this research shows that TOHB can reduce AR expression and increase serum SOD levels in SOPK mouse models with insulin resistance. This finding can be suggested in further research that TOHB is the basis for treating PCOS cases with insulin resistance.

Author: Budi Santoso, Widjiati , Ahmad Syaifuddin Zuhri, Firas Farisi Alkaff

Link: Journal of International Dental and Medical Research ISSN 1309-100X Hyperbaric Oxygen Therapy http://www.jidmr.com Budi Santoso and et al Volume ∙ 13 ∙ Number ∙ 1 ∙ 2020 Page 147.

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