Ameliorative effect of recombinant human lactoferrin on the premature ovarian failure in rats after cyclophosphamide treatments

Abstract

This study investigated the effect of recombinant human lactoferrin (rhLF) on the premature ovarian failure (POF) of rats. After cyclophosphamide treatments, the POF rats were divided into the following groups: normal control group (NC), low-dose group (LD), medium-dose group (MD) and high-dose group (HD) of rhLF. After drug administrations, the ovarian indexes and hormonal levels were detected. After follicle number count, the proliferation and apoptosis were analyzed with the expressions of genes related with oogenesis, reactive oxygen species (ROS) production and apoptosis detected, followed by the calculation of oxidative stress and protein expressions. After 4-hydroperoxy cyclophosphamide (4-HC) treatments, the effect of rhLF on the proliferation, ROS production and gene expressions of primary rat granulosa cells (GCs) cultured in vitro were detected. After mating, the fertilities of POF rats were recorded. The result showed that the rhLF administrations up-regulated the ovarian index with the number of developing follicles increased and the decreases of hormonal levels conferred. The Ki-67 intensities of the MD and HD groups were up-regulated with the Tunnel intensities decreased. The rhLF treatments significantly promoted the expression of oogenesis, antioxidant and anti-apoptosis related genes. The expression of Bax and Caspase 3 were decreased with the expression of Bcl-2 up-regulated after rhLF administrations. The in vitro treatments of rhLF effectively conferred the toxicity of 4-HC on primary rat GCs. The fertility assessment showed the rhLF treatments up-regulated the offspring’s’ folliculogenesis, which confirmed the ameliorative role of rhLF on the POF damages via the inhibition of ROS production in GCs.

Melatonin Protects Against Cyclophosphamide-induced Premature Ovarian Failure in Rats

“…Many studies have shown that CTX causes ovarian dysfunction including accelerated loss of ovarian reserve, folliculogenesis dysregulation, and steroid disorder. 3,4,16 We found that the serum FSH and LH levels were significantly increased and the E2 and P levels were decreased in rats treated with CTX. The number of atretic follicles was increased by the CTX treatment; conversely, the decreased number of primordial, primary, and secondary follicles resulted in a decreased number of total follicles, which was in line with a previous report.…”

“…The CTX-induced POF rats model was established according to the previous studies. 16,17 The rats of the POF, MT10, and MT20 groups were intraperitoneally injected with 50 mg/kg of CTX on the first day and then 8 mg/kg for 15 consecutive days, while the control group was injected with 0.9% saline instead of CTX. The rats of the MT10 and MT20 groups were injected with melatonin (Sigma, St. Louis, MO, USA) at 10, or 20 mg/kg body weight (i.p.…”

The evaluation of sea cucumber (Acaudina leucoprocta) peptide on sex hormone regulation in normal and premature ovarian failure female mice

“…55 In addition, S. B. Li et al reported that the oral administration of recombinant human lactoferrin alleviated cyclophosphamide-induced POF symptoms by increasing the hormone levels of E2 and AMH and inhibiting apoptosis. 56 It is speculated that the potential regulatory effects of proteins and protein derivatives on sex hormones may be related to their amino acid composition. The total peptide content of SCP reached 808.24 mg g −1 , and the 6 amino acids with the highest content were Gly (24.35%) > Glu (15.45%) > Ala (11.45%) > Pro (10.28%) > Arg (7.44%) (data not shown).…”

“…Moreover, AMH plays an important role in follicular development and is an important marker of follicular health. 53 56 It is speculated that the potential regulatory effects of proteins and protein derivatives on sex hormones may be related to their amino acid composition. The total peptide content of SCP reached 808.24 mg g −1 , and the 6 amino acids with the highest content were Gly (24.35%) > Glu (15.45%) > Ala (11.45%) > Pro (10.28%) > Arg (7.44%) (data not shown).…”

Alleviation of Oxidative Stress in Dental Pulp Cells Following 4-Hexylresorcinol Administration in a Rat Model

“…Therefore, antioxidant administration would be helpful to alleviate oxidative stress for these patients. Lactoferrin (LF) is a well-known antioxidant [29]. LF incorporated titanium disc improves antibacterial and osteoinductive ability of dental implant [30].…”