Proposed mechanisms of low-level light therapy in the treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a global challenge, affecting a large number of people worldwide. Efficacy of the existed treatments can barely meet the demands of patients. Patients who are poorly responding to those treatments are seeking for a more effective and suitable technique to treat their disease. Low-level light therapy (LLLT) is a newly developed technique, which has been proved to stimulate hair growth. Based on the function principle of LLLT in other domains and refer to the published literatures, we write this review to neaten and elucidate the possible mechanism of LLLT in the treatment of AGA. A review of published literature which is associated with keywords LLLT, photobiomodulation, AGA, treatment, hair growth, and mechanism was performed to elucidate the proposed mechanism of LLLT in the treatment of AGA. The present study shows that LLLT can accelerate hair growth in AGA patients. The proposed mechanism of LLLT in treating AGA may vary among different specialists. But we can summarize the consensual mechanisms as follows; low-level light absorbed by chromophores can lead to the production of nitric oxide (NO) and the modulation of reactive oxygen species (ROS). These mobilized molecules subsequently activate redox-related signaling pathways in hair follicle cells and perifollicular cells. Finally, these activated cells participate in the regrowth of hair follicle. Even though the efficacy of LLLT in the treatment of AGA in both men and women has already been confirmed, the present studies focusing on discovering LLLT are still inadequate and unsystematic. More studies are needed to standardize the optimum treatment parameters applied in promoting hair growth and determine the long-term safety and efficacy of LLLT. Current recognitions about the mechanisms of LLLT, mainly focused on the molecules that may take effect, neglected different cellular components that are functional in the hair follicle macro-environment.

Low level laser therapy (LLLT) modulates ovarian function in mature female mice.

It is known that LLLT has beneficial effects on several pathological conditions including wound healing, pain and inflammation. LLLT modulates biological processes, including cell proliferation, apoptosis and angiogenesis. In the present study, we examined the effect of local application of LLLT on follicular dynamics, ovarian reserve, AMH expression, progesterone levels, apoptosis, angiogenesis, and reproductive outcome in adult mice. LLLT (200 J/cm2) increased the percentage of primary and preantral follicles, whilst decreasing the percentage of corpora lutea compared to control ovaries. LLLT-treated ovaries did not exhibit any changes regarding the number of primordial follicles. We observed a higher percentage of AMH-positive follicles (in early stages of development) in LLLT-treated ovaries compared to control ovaries. LLLT reduced the P4 concentration and the apoptosis in early antral follicles compared to control ones. LLLT caused a reduction in the endothelial cell area and an increase in the periendothelial cell area in the ovary. Additionally, LLLT was able to improve oocyte quality. Our findings suggest that local application of LLLT modulates follicular dynamics by regulating apoptosis and the vascular stability in mouse ovary. In conclusion, these data indicate that LLLT might become a novel and useful tool in the treatment of several pathologies, including female reproductive disorders.

How do red and infrared low-level lasers affect folliculogenesis cycle in rat's ovary tissue in comparison with clomiphene under in vivo condition.

Folliculogenesis is a cycle that produces the majority of oocyte. Any disruption to this cycle leads to ovulation diseases, like polycystic ovarian syndrome (PCOS). Treatments include drugs and surgery; lasers have also been used complementarily. Meanwhile, still there is no definite treatment for PCOS. This study investigated the photo-bio stimulation effect of near-infrared and red low-level laser on producing follicles and compared the result with result of using common drug, clomiphene. Therefore, the aim of this study was to propose the use of lasers autonomously treatment. So, there was one question: how do lasers affect folliculogenesis cycle in rat's ovary tissue? In this study, 28 rats were assigned to four groups as follows: control (CT), clomiphene drug (D), red laser (RL), and near-infrared laser (NIRL). Afterwards, 14 rats of RL and NIRL groups received laser on the first 2 days of estrous cycle, each 6 days, for 48 days. During treatment period, each rat received energy density of 5 J/cm2. Seven rats in D group received clomiphene. After the experiment, lasers' effects at two wavelengths of 630 and 810 nm groups have been investigated and compared with clomiphene and CT groups. Producing different follicles to complement folliculogenesis cycle increased in NIRL and RL groups, but this increase was significant only in the NIRL group. This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS.

Charged iron particles, components of space radiation, destroy ovarian follicles.

STUDY QUESTION: Do charged iron particles, components of space radiation, cause premature ovarian failure? SUMMARY ANSWER: Exposure to charged iron particles causes ovarian DNA damage, oxidative damage and apoptosis, resulting in premature ovarian failure. WHAT IS KNOWN ALREADY: The ovary is very sensitive to follicle destruction by low linear energy transfer (LET) radiation, such as X-rays and γ-rays. However, it is completely unknown whether high-LET radiation, such as charged iron particles, also destroys ovarian follicles. STUDY DESIGN, SIZE, DURATION: Twelve week old C57BL/6J female mice were exposed to single doses of 0, 5, 30 or 50 cGy (n = 8/group) charged iron particles (LET = 179 keV/µm) at energy of 600 MeV/u. Two groups were irradiated at the highest dose, one fed AIN-93M chow and the other fed AIN-93M chow supplemented with 150 mg/kg diet alpha lipoic acid (ALA). PARTICIPANTS/MATERIALS, SETTING, METHODS: We quantified the numbers of ovarian follicles, measured serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations, and analyzed histone H2AX phosphorylation, oxidative damage and apoptosis markers in the ovarian follicles. MAIN RESULTS AND THE ROLE OF CHANCE: H2AX phosphorylation, lipid peroxidation, protein nitration and apoptosis were highly induced in ovarian follicles at 6 h and remained increased 1 week after irradiation. As a result, numbers of healthy ovarian follicles were significantly and dose-dependently depleted at 1 and 8 weeks post-irradiation, with 57, 84 and 99% decreases in primordial follicles at 8 weeks at the 5, 30 and 50 cGy doses, respectively (P < 0.05 versus 0 cGy). Consistent with near-total depletion of ovarian follicles in the 50 cGy group, serum concentrations of FSH and LH were significantly elevated at 8 weeks. Dietary supplementation with ALA partially prevented the adverse ovarian effects of 50 cGy iron particles. LIMITATIONS, REASONS FOR CAUTION: About 21% of the estimated radiation dose from exposure to galactic cosmic rays during a multi-year Mars mission will be due to high-LET particles, of which iron is only one. The effects of galactic cosmic rays, which contain a mixture of multiple charged particles, as well as protons, neutrons, and helium ions, may differ from the effects of iron alone. WIDER IMPLICATIONS OF THE FINDINGS: We show for the first time that charged high-LET ions are highly damaging to the ovary even at low doses, causing premature ovarian failure. In addition to raising concerns for female astronauts, these findings raise concerns for ovarian damage due to clinical uses of high-LET particles for cancer treatment. In addition to causing infertility, premature ovarian failure has adverse implications for the functions of heart, brain, bone and muscle later in life. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a National Aeronautics and Space Administration grant NNX14AC50G to U.L. B.M. was partially supported by a National Space Biomedical Research Institute First Award, PF04302. Additional support was received from the University of California Irvine Center for Occupational and Environmental Health. The authors have no conflicts of interests.

Ameliorative effects of resveratrol on acute ovarian toxicity induced by total body irradiation in young adult rats.

OBJECTIVE: The purpose of this study was to investigate the ovarian protective effects of resveratrol in rats exposed to total body irradiation. DESIGN: Experimental study. SETTINGS: University hospital. PARTICIPANTS AND INTERVENTIONS: Thirty female rats were randomized into four groups: (1) control group (n = 7); (2) low-dose (10 mg/kg) resveratrol group (n = 8); (3) high-dose (100 mg/kg) resveratrol group (n =7); and (4) sham irradiation group (n = 8). The drugs were administered intraperitoneally as single doses, and the rats were exposed to total body radiation 24 h after the treatment. The animals were sacrificed the following day, and their ovaries were excised for histopathological and biochemical analysis. MAIN OUTCOME MEASURES: The ovarian follicle counts were calculated, and irradiation-dependent ovarian damage and tissue levels of antioxidant enzymes were evaluated. RESULTS: Group 2 and Group 3 showed significantly higher numbers of total follicle counts compared with Group 1 (P < 0.01). The low-dose resveratrol treatment was associated with significantly higher numbers of primary follicles than the high-dose group. The tissue activities of glutathione peroxidase (GsH-Px) and catalase (CAT) were significantly elevated in the resveratrol-treated animals. Evaluation of ovarian histology revealed no remarkable changes in fibrosis and leucocyte infiltration among the resveratrol-treated and control rats; however, vascularity was significantly reduced in the high-dose group (P = 0.014). CONCLUSION: Resveratrol attenuated irradiation-dependent ovarian damage, suggesting that this natural antioxidant is effective in reducing the follicle loss induced by ionizing radiation.

Unaltered development of the initial follicular waves and normal pubertal onset in female rats after neonatal deletion of the follicular reserve.

In rats, the pool of primordial follicles is established within the first 3 d postnatally (dpn). Immediately after their differentiation, a subset of follicles begins to grow and constitutes the initial follicular waves. In this study we investigated the development of these early growing follicles after deletion of the primordial follicle pool induced by 1.5 Gy gamma-irradiation at 5 dpn. Within only 24 h, i.e. at 6 dpn, 99% of the primordial follicles disappeared, whereas most of the growing follicles remained unaffected. The study of these surviving follicles throughout the immature period has shown that their subsequent growth proceeded normally, as assessed by proliferating cell nuclear antigen immunostaining and follicular counts. No modification in the process of follicular atresia, studied by terminal deoxynucleotidyltransferase-mediated deoxy-UTP-fluorescein nick end labeling and Southern blot of DNA fragmentation analysis, was observed. Complementary analysis, by either in situ hybridization for inhibin subunits, P450 aromatase, and LH receptor mRNAs or plasma dosages of 17beta-estradiol and inhibin B, further showed that follicular maturation was unaltered. In line with these observations, pubertal onset was normal, regarding both age and ovulation rate. Nevertheless, as a consequence of the nonrenewal of the growing pool, the follicular complement was practically exhausted at puberty, and 90% of the females evidenced sterility by 4 months. Altogether, our results demonstrate that the deletion of the primordial follicle pool has induced no modification in the growth pattern of the early growing follicles that develop as their counterparts in control ovaries. Within the immature period, the initial follicular waves ensure the ovarian functionality and thus play a key role in the initiation of reproductive life.