Assessment of the therapeutic potential of lutein and beta-carotene nanodispersions in a rat model of fibromyalgia.

Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and cognitive impairment. Despite the availability of various treatment options, FM remains a challenging condition to manage. In the present study, we investigated the efficacy of formulated nanodispersions of lutein and beta-carotene in treating FM-related symptoms induced by reserpine in female Wistar rats. Several techniques have been implemented to assess this efficacy at various levels, including biochemical, bioelectrical, and behavioral. Namely, oxidative stress markers, monoamine levels, electrocorticography, pain threshold test, and open field test were conducted on control, FM-induced, and FM-treated groups of animals. Our results provided compelling evidence for the efficacy of carotenoid nanodispersions in treating FM-related symptoms. Specifically, we found that the dual action of the nanodispersion, as both antioxidant and antidepressant, accounted for their beneficial effects in treating FM. With further investigation, nano-carotenoids and particularly nano-lutein could potentially become an effective alternative treatment for patients with FM who do not respond to current treatment options.

Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy.

Epilepsy is one of the most frequent neurological disorders characterized by an enduring predisposition to generate epileptic seizures. Oxidative stress is believed to directly participate in the pathways of neurodegenerations leading to epilepsy. Approximately, one-third of the epileptic patients who suffer from seizures do not receive effective medical treatment. Sodium valproate (SVP) is a commonly used antiepileptic drug (AED); however, it has toxic effects. Lutein (L), a carotenoid, has potent antioxidant and anti-inflammatory properties. The aim of this study was to determine the neuroprotective effect of sodium valproate (SVP) and lutein (L) in a rat model of pilocarpine- (PLC-) induced epilepsy. To achieve this aim, fifty rats were randomly divided into five groups. Group I: control, group II: received PLC (400 mg/kg intraperitoneally), group III: received PLC + SVP (500 mg/kg orally), group IV: received PLC + SVP + L (100 mg/kg orally), and group V: received (PLC + L). Racine Scale (RC) and latency period to onset seizure were calculated. After eight weeks, the hippocampus rotarod performance and histological investigations were performed. Oxidative stress was investigated in hippocampal homogenates. Results revealed that SVP and L, given alone or in combination, reduced the RC significantly, a significant delay in latency to PLC-kindling onset, and improved rotarod performance of rats compared with the PLC group. Moreover, L was associated with a reduction of oxidative stress in hippocampal homogenate, a significant decrease in serum tumor necrosis factor-alpha (TNF-α) level, and inhibition of cerebral injury and displayed antiepileptic properties in the PLC-induced epileptic rat model. Data obtained from the current research elucidated the prominent neuroprotective, antioxidant, and anti-inflammatory activities of lutein in this model. In conclusion, lutein cotreatment with AEDs is likely to be a promising strategy to improve treatment efficacy in patients suffering from epilepsy.

Fatty acids modulate the efficacy of lutein in cataract prevention: Assessment of oxidative and inflammatory parameters in rats.

BACKGROUND: Effects of lutein (L) and fatty acids [linoleic acid (LA), eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) and oleic acid (OA)] on oxidative stress and inflammation in cataract were assessed. METHODS: Cataract was induced in male Wistar rat pups (11 days old) by giving a single dose of sodium selenite (25 µM/kg body weight) by IP. Lutein (1.3 µmol/kg body weight) was given one day before and five days after selenite injection as a micelle with 7.5 mM LA, or 7.5 mM EPA + DHA or 7.5 mM OA. Serum and lens oxidative stress and inflammatory parameters having a bearing cataract were assessed. RESULTS: Serum and lens nitric oxide, MDA and protein carbonyls were significantly (p < 0.05) increased in cataract compared to control and experimental groups. Catalase, SOD, glutathione peroxidase and glutathione transferase activity and glutathione level in serum and lens of cataract group were significantly (p < 0.05) decreased. Serum eicosanoids (PGE2, LTB4, and LTC4) and cytokines (CRP, TNF-α, IL1-ß, and MCP-1) were significantly (p < 0.05) increased in cataract. The activity of cPLA2 and Cox-2 in cataract lens was higher (p < 0.05) compared to other groups. EP-1, NOS-2 and NF-kB expression were higher (p < 0.05) in cataract. The ratio of water insoluble to water soluble protein was increased in cataract lens. Group administered with L + EPA + DHA exhibited highest cataract prevention compared to L + LA and L + OA. Pups given lutein with EPA + DHA had the highest amount of lutein in the lens. CONCLUSIONS: The anti-cataract activity of lutein was influenced by fatty acids and found to be highest with EPA + DHA compared to LA or OA.

Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289].

BACKGROUND: There is no generally accepted medical or surgical treatment to stop the progressive course of retinitis pigmentosa. Previous studies have suggested lutein as a potential treatment with positive effects on macular pigment density. The objective of this study was to examine the effect of lutein supplementation on preservation of visual function in patients with retinitis pigmentosa (RP) METHODS: In a double-masked randomized placebo-controlled phase I/II clinical trial with a cross-over design, 34 adult patients with RP were randomized to two groups. One group, consisted of 16 participants, received lutein supplementation (10 mg/d for 12 wks followed by 30 mg/d) for the first 24 weeks and then placebo for the following 24 weeks, while the other group included 18 participants for whom placebo (24 weeks) was administered prior to lutein. Visual acuity, contrast sensitivity, and central visual field were measured at different illumination levels at baseline and every week using a PC-based test at home. RESULTS: For visual acuity (VA) at normal illumination level, treatment with lutein reduced logMAR, i.e. improved VA, but this effect was not statistically significant. The changes in normal (100%), low (4%), and very low (0.1%) illumination log CS were not statistically significant (p-values: 0.34, 0.23, and 0.32, respectively). Lutein had a statistically significant effect on visual field (p-value: 0.038) and this effect increased in the model assuming a 6-week delay in effect of lutein. Comparing the development of vision measures against the natural loss expected to occur over the course of 48 weeks, most measures showed reduced decline, and these reductions were significant for normal illumination VA and CS. CONCLUSION: These results suggest that lutein supplementation improves visual field and also might improve visual acuity slightly, although these results should be interpreted cautiously. As a combined phase I and II clinical trial, this study demonstrated the efficacy and safety of lutein supplementation.

Influence of short-term antioxidant supplementation on macular function in age-related maculopathy: a pilot study including electrophysiologic assessment.

PURPOSE: To evaluate the influence of short-term antioxidant supplementation on retinal function in age-related maculopathy (ARM) patients by recording focal electroretinograms (FERGs). DESIGN: Nonrandomized, comparative clinical trial. PARTICIPANTS: Thirty patients with early ARM and visual acuity >/=20/30, divided into two groups, similar for age and disease severity: antioxidant group (ARM-A, n = 17) and no treatment group (ARM-NT, n = 13). Eight age-matched normal subjects divided into antioxidant (N-A, n = 4) or no treatment (N-NT, n = 4) groups. METHODS: ARM-A patients and N-A patients had oral supplementation of lutein, 15 mg; vitamin E, 20 mg; and nicotinamide, 18 mg, daily for 180 days, whereas ARM-NT patients and N-NT patients had no dietary supplementation during the same period. Eight of the 17 ARM-A patients took supplementation for an additional 180-day period. In all patients and normal subjects, FERG assessment was performed at the study entry (baseline) and after 180 days. Further testing was performed at 360 days for the eight ARM-A patients taking supplements and for one ARM-A patient who had discontinued supplementation after 180 days. FERGs were recorded in response to a 41-Hz sinusoidally modulated uniform field (93.5% modulation depth) presented to the macular region (18 degrees ) on a light-adapting background. In a subgroup of patients (11 ARM-A and 5 ARM-NT), whose responses had suitable signal-to-noise ratios, FERGs were also recorded at different stimulus modulation depths between 8.25% and 93.5%. MAIN OUTCOME AND MEASURES: Amplitude (in micro V) and phase (in degrees) of the FERG fundamental harmonic component. FERG modulation thresholds, estimated from the value of log modulation depth yielding a criterion response. RESULTS: At 180 days, FERGs of ARM-A patients and N-A patients were increased in amplitude (mean change, 0.11 and 0.15 log micro V, respectively, P