Parkinson\'s disease (PD) is an idiopathic disease caused by the loss or degeneration of the dopaminergic (dopamine-producing) neurons in the brain and characterized by various inflammatory and apoptotic responses in the neuronal cells. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) axis is responsible for neuronal survival by providing a number of anti-inflammatory and anti-apoptotic milieu that prevent the progression of PD. Alpha-lipoic acid (ALA) is a natural cofactor that has antioxidant capacity and contributes to various metabolic processes. ALA can penetrate the blood-brain barrier and contribute to numerous neuroprotective effects. It can activate PI3K/AKT pathway with consequent reduction of different inflammatory and oxidative biomarkers. Our work aims to unfold the neuroprotective effects of ALA via targeting PI3k/AKT pathway. Forty male mice were divided into four groups: control, ALA (100 mg/kg/day; i.p.), rotenone (ROT) (1.5 mg/kg/2 days, i.p.) and rotenone + ALA for 21 days. ALA showed obvious neuroprotective effects via significant activation of PI3K/AKT pathway with subsequent decreasing level of Caspase-3. ALA resulted in prominent anti-inflammatory actions by decreasing interlukin-1β (IL-1β), tumor necrosis factor (TNF)-α and nuclear factor kabba (NFk)-B. ALA remarkably induced antioxidant activities via increasing reduced glutathione (GSH) and superoxide dismutase (SOD) levels as well as decreasing malondialdehyde (MDA) level. The substantial behavioral improvement reflected in these results was noticed in the ALA-treated mice as a reflection of the neuroprotective activities of ALA. In conclusion, ALA showed promising neuroprotective effects in rotenone-induced PD via activating the PI3K/AKT pathway and consequent inhibition of apoptotic and inflammatory biomarkers.

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage.

Gentamicin is an aminoglycoside antibiotic with a rapid bactericidal effect on the treatment of many infections. However, its use at high concentrations for more than 7 days causes nephrotoxic side effects. This study investigated the potential of Resatorvid and alpha lipoic acid (ALA) in mitigating gentamicin-induced nephrotoxicity in rats, considering biochemical, histopathological, and molecular parameters. This study randomly distributed 34 Wistar albino rats into four groups: healthy control (n = 6), Gentamicin (80 mg/kg, n = 7), Gentamicin + Sham (%10 hydroalcoholic solution, n = 7), Gentamicin + Resatorvid (5 mg/kg, n = 7), and Gentamicin + ALA (100 mg/kg, n = 7). Resatorvid treatment led to a statistically significant decrease in urinary IL-18, KIM-1, and NGAL levels, whereas ALA treatment significantly reduced KIM-1 levels compared to the gentamicin-only group. Both Resatorvid and ALA showed partial reductions in urine creatinine levels. Moreover, treatments with Resatorvid and ALA resulted in statistically significant decreases in NRF-2, CAS-3, and NR4A2 expressions. However, only Resatorvid demonstrated a statistically significant decrease in NF-B expression. These findings highlight the potential of Resatorvid in ameliorating gentamicin-induced nephrotoxicity, thereby expanding the therapeutic utility of gentamicin and enhancing its efficacy against infections.

Over three years since the World Health Organization (WHO) declared COVID-19 a pandemic, it is still a global burden. Vaccines against COVID-19, caused by SARS-CoV-2, are available and effective for preventing disease. However, their protective effects are not 100%. Currently, the U.S. Food and Drug Administration (FDA) has only approved a limited number of inpatient treatments for COVID-19, such as remdesivir, baricitinib, and tocilizumab. These medications have indications and contraindications applicable to a select patient population. Finding additional effective therapies that are widely available with limited risk could be vital in optimizing treatment strategies for this viral illness. Some vitamins and supplements have been identified as potential options for managing COVID-19. Vitamin D (VD) deficiency has been associated with respiratory tract infections. Moreover, alpha-lipoic acid (ALA) is a powerful antioxidant and helps reduce inflammatory responses in many pathologic conditions. This review aims to analyze the current evidence regarding the effectiveness of VD and alpha-lipoic acid in COVID-19 infection in both outpatient and hospitalized patients. Relevant randomized controlled trials (RCTs) were identified via the PubMed database from January 1, 2021, to December 31, 2023. Inclusion criteria were as follows: the study design was a randomized controlled trial (RCT), the usage of a constant dose during the intervention period without any additional boluses, and a research ethics committee approved it. Exclusion criteria included a lack of an outcome or apparent intervention, additional boluses, or a single-dose regimen in all the interventional groups. There were 11 studies with a total sample size of 35,717 patients that met the criteria for this review. A total of 10 RCTs examined the efficacy of VD, and one RCT that reviewed the efficacy of ALA was identified. All of the articles investigated the use of VD or ALA during the treatment of COVID-19. The endpoints of each study varied, including length of stay in hospital, viral load, SARS-CoV-2 infection rate, mechanical ventilation, inflammatory markers, clinical symptoms, Sequential Organ Failure Assessment (SOFA) score, and mortality. In 8/10 VD supplementation trials, significant differences were identified between the interventional and placebo groups in the aforementioned parameters. In 2/10 VD supplementation trials, no significant differences were identified. The ALA supplementation RCT found no differences between the interventional and placebo groups in the SOFA score and 30-day all-cause mortality rate. The current literature suggests that VD can potentially reduce the SARS-CoV-2 infection rate, oxygen requirements, inflammatory markers, clinical symptoms, and mortality. Regarding ALA, although there was a suggestion of benefit, it was not statistically significant. Common limitations among the different studies included relatively small sample sizes, different geographical patient locations among studies, and differences in dosages. Trials investigating the effects of higher doses of VD supplementation on SARS-CoV-2 infection should be conducted. More research is needed to define best practices and optimal dosing protocols for the use of VD in COVID-19.

UNASSIGNED: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients.
UNASSIGNED: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated.
UNASSIGNED: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease.
UNASSIGNED: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

BACKGROUND: Ovarian cancer is the leading cause of gynecological cancer deaths. One of the major challenges in treating ovarian cancer with chemotherapy is managing the resistance developed by cancer cells to drugs, while also minimizing the side effects caused by these agents In the present study, we aimed to examine the effects of a combination of alpha lipoic acid (ALA), with cisplatin and paclitaxel in ovarian cancer(OVCAR-3).
METHODS: The cytotoxic effects of ALA, cisplatin and paclitaxel on OVCAR-3 cells were determined. Four groups were formed: Control, ALA, Cisplatin + Paclitaxel, ALA + Cisplatin + Paclitaxel. The effects of single and combined therapy on cell migration, invasion and colony formation were analyzed. Changes in the expression of genes related to apoptosis, cell adhesion and cell cycle were analyzed with Real-time polymerase chain reaction(RT-PCR). The oxidative stress index and The Annexin V test were performed.
RESULTS: The reduction in rapamycin-insensitive companion of mTOR(RICTOR) expression in the ALA + Cisplatin + Paclitaxel group was found statistically significant(p < 0.05). The decrease in MMP-9 and - 11 expressions the ALA + Cisplatin + Paclitaxel group was statistically significant(p < 0.05). The lowest values for mitogen-activated protein kinase(MAPK) proteins were found in the ALA + Cisplatin + Paclitaxel group. No colony formation was observed in the Cisplatin + Paclitaxel and ALA + Cisplatin + Paclitaxel groups. The lowest wound healing at 24 h was seen in the ALA + Cisplatin + Paclitaxel group.
CONCLUSIONS: This study is the first one to investigate the combined treatment of ALA, Cisplatin, Paclitaxel on OVCAR-3. While ALA alone was not effective, combined therapy with ALA, has been found to reduce cell invasion, especially wound healing in the first 24 h, along with tumor cell adhesion.

OBJECTIVE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.
METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin\' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.
RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.
CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.

Cytarabine, an anti-metabolite drug, remains the mainstay of treatment for hematological malignancies. It causes various toxic effects including teratogenicity. Alpha lipoic acid (ALA) is a natural antioxidant reported to offer protection against hepatotoxicity induced by various pathological conditions, drugs, or chemicals. We investigated the protective effect of ALA against prenatal cytarabine exposure-induced hepatotoxicity in rat female neonates. A total of 30 dams were randomly assigned to five groups and received normal saline, ALA 200 mg/kg, cytarabine 12.5 mg/kg, cytarabine 25 mg/kg, and cytarabine 25 mg/kg + ALA 200 mg/kg, respectively, from gestational day (GD)8 to GD21. Cytarabine and ALA were administered via intraperitoneal and oral (gavage) routes, respectively. On postnatal day (PND)1, all the live female neonates (pups) were collected and weighed. The blood and liver from pups were carefully collected and used for histopathological, and biochemical evaluations. A significant and dose-dependent decrease in maternal food intake and weight gain was observed in the pregnant rats (dams) of the cytarabine groups as compared to the dams of the control group. The pups exposed to cytarabine showed a significant and dose-dependent (a) decrease in body weight, liver weight, hepatosomatic index, catalase, superoxide dismutase, glutathione, glutathione peroxidase, serum albumin levels and (b) increase in malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, AST/ALT ratio, and histopathological anomalies. Maternal co-administration of ALA ameliorated these biochemical changes and histopathological abnormalities by combating oxidative stress. Future studies are warranted to explore the molecular mechanisms involved in the ALA\'s protective effects against prenatal cytarabine-induced hepatotoxicity.

Aim Acute carpal tunnel syndrome (ACTS) is a well-recognized and common condition following a distal radius fracture. The aim of this study was to test deflazacort associated with Nevridol®800 or deflazacort alone in order to prevent moderate or severe ACTS after the distal radius fracture in adults. Methods Sixty-four patients suffering from extraarticular wrist fractures were divided into three groups. The first group (n=26) was treated by plaster cast. The second group (n=20) was treated by cast and deflazacort (heterocyclic glucocorticoids prodrug belonging to the class of oxazoline steroids) 30 mg/day for 15 days. The third group (n=18) was treated by cast and deflazacort 30 mg/ day for 15 days + Nevridol (food supplements) 800 mg a day for 40 days. The criteria to evaluate the patients were: the complication of ACTS, the duration of symptoms, the functional results were evaluated according to The Disabilities of the Arm, Shoulder and Hand (DASH) life correlated with wrist function by the Short Form 12 Health Survey (SF-12), and positive Tinel and Phalen test. The correlation between ACTS signs and volar tilt in the latero-lateral at X-rays in the three studied groups was assessed. The endpoints were set on 7 days, 15 days, 1 months, 2 months and 3 months after a trauma. Results In the first group, 12 of 26 (46.15%) and the second group 7 of 20 (35%) patients suffered from ACTS, while in the third group only two of 18 (11%) patients (p=0.033). After 3 months of treatment, the third group had better results in DASH (p=0.034), SF-12 (p=0.044), Tinel (0.045) and Phalen (0.048) tests. Conclusion Deflazacort associated with Nevridol 800 may reduce the prevalence of postoperative median nerve dysfunction.