PCOS is a common, clinically heterogeneous endocrine disorder, which is associated with endocrinopathy and metabolic abnormalities [10]. Ovulatory dysfunction, polycystic ovarian morphology, insulin resistance and hyperandrogenism are the typical characteristics [2]. More and more studies found that PCOS is associated with chronic inflammation and oxidative stress [2–4, 11]. Glutamine is the most abundant free amino acid in human circulation [12]. It is an important source of energy and a precursor of glutathione, and plays an essential role in several metabolic processes, such as protein and nucleic acid synthesis [13], and it also has anti-inflammatory and antioxidant effects as reported by previous studies [7, 8].
In the present study, the hormones and ovarian morphology changes in the DHEA-induced PCOS and PCOS + glutamine rats were in accordance with the characteristic of PCOS patients as previous studies [2, 9]. Significant decrease in the level of some amino acids including glutamine was observed in plasma in PCOS patients compared with the controls, these changes reflect the various metabolic pathways that participate in physiological functions [10]. However, there is rare studies about glutamine on hormones and ovaries. Olaniyi et al [12] found that glutamine can attenuate the decrease of the serum concentrations of FSH, LH and T in cadmium-treated male rats for a consecutive 30 days' administration. Gholipour et al [14] reported that diet supplementing with L-glutamine for 40 days significantly increased levels of FSH and LH in guinea fowls. Our study also showed that T concentration was increased by the supplementation of glutamine in PCOS rats, and it increased with the dosage of the glutamine, but the LH concentration was decreased by supplementation of glutamine, even more, the concentration of FSH, E2, P and the ovaries didn't show obvious changes among these different groups. That may due to the short duration of glutamine administration (only twice in one day in this study), and it may need a longer time to recover the changes of hormones and ovarian morphology in PCOS.
Previous studies reported that there is low-grade inflammation associated with PCOS [10, 15], and our study found that serum inflammation factors levels, such as IL-6, IL-18, TNF-α and CRP, were significantly elevated in PCOS rats. Previous studies showed that the agents such as curcumin [15], caffeine with epigallocatechin or green tea extract [16] which have anti-inflammatory effects can improve the the low-grade inflammation state by decreasing the levels of TNF-α, IL-6 and CRP, including the PCOS rats. Glutamine also showed an anti-inflammation effect in inflammatory diseases, the treatment with glutamine has the potential to decrease of inflammatory cytokines [17].
Glutamine can attenuate muscle inflammation, maintaining the concentration of muscle TNF-α, IL-6 and IL-10 close to basal levels observed in the control group [8], glutamine supplementation following traumatic brain injury could inhibit NF-kB activation and down-regulate pro-inflammatory cytokine expression (TNF-α, IL-1b and IL-6) [18], and it also could decrease intestinal and plasma TNF-α in the induced intestinal inflammation rats [19]. Moreover, glutamine could decrease IL-6 in the intestine in human volunteers [20]. In the present study, the serum concentrations of IL-6, IL-18, TNF-α and CRP in PCOS rats were significantly decreased by supplementation of glutamine, especially in the 0.5 g/kg group and 0.75 g/kg group, which indicated glutamine could also attenuate the low-grade inflammation of PCOS.
A lot of studies have revealed that oxidative markers in circulation are significantly increased in PCOS patients compared with the normal controls and a crucial role in the PCOS pathogenesis is played by oxidative stress [3, 4]. Oxidative stress is considered as the imbalance between oxidants and antioxidants and the increased production of reactive oxygen species (ROS) [4]. In the present study, some serum oxidative markers were detected and the results showed that serum concentrations of SOD were significantly lower in PCOS groups, MDA, NO and NOS were significantly higher in PCOS group compared with the control group, which was consistent with previous study on PCOS patients [21]. These findings dedicated that there is an oxidative stress in these DHEA-induced PCOS rats. Furthermore, results of the present study showed that the supplementation of glutamine with doses of 0.5 g/kg and 0.75 g/kg in PCOS rats could significantly increase the serum concentrations of SOD and maintain the concentrations of MDA, NO and NOS to basal levels observed in the control rats, all of these showed the antioxidant effects of glutamine. The effects of glutamine on improving antioxidant ability have been indicated in previous studies. Nemati et al [7] reported that supplementation of glutamine can reduce oxidative stress and improve the antioxidant system of healthy adult males after an exhaustive exercise. Szpetnar et al [22] found that glutamine is effective in reducing manganese-induced oxidative stress by increasing glutathione peroxidase and SOD activity and decreasing in MDA level.