Vitamin D3 and zinc supplements augment the antimanic efficacy of lithium and olanzapine treatments in an animal model of mania.

Objective: Bipolar disorder (BD) is a challenging psychiatric disorder and a complex disease. The associated reduction in serum vitamin D3 (VitD3) levels in BD patients and the contribution of zinc (Zn) to the treatment, along with the severe side effects of lithium (Li) treatment, were encouraging to assess the efficacy of different correlated combinations of therapeutic/nutraceutical treatments such as olanzapine (Oln), VitD3, and Zn against Li. Methods: Mania was induced in C57BL/6 mice by administering methylphenidate (MPH) for 14 consecutive days. On the 8th day of MPH injection, different treatment regimens were administered, Li, Oln, VitD3/Zn, VitD3/Zn/Oln, VitD3 + Zn + Oln + Li50mg/kg (C50), and VitD3 + Zn + Oln + Li100mg/kg (C100). Both VitD3 (850 IU/kg) and Zn (180 mg/kg) were supplied with food for 2 weeks before starting the induction of mania, which continued until the end of MPH administration. Behavioral, brain oxidative stress, thyroid hormones, VitD3, Zn, GsK-3ß, and Bcl2 levels, as well as brain histopathological alterations, were assessed. Results: Manic mice exhibited alterations in all tested parameters, and the histopathological examination of the cortex and hippocampus confirmed these results. The VitD3/Zn/Oln, C50, and C100 treatment regimens reversed most of the behavioral and pathophysiological alterations; however, the C50 treatment regimen was the most efficient. Conclusions: This study emphasizes the importance of combining different antimanic medications like Li and Oln with nutraceutical supplements to increase their antimanic efficacy, reduce their adverse effects, and, ideally, improve the BD patient's quality of life.

Assessment of the Oxidative Damage and Genotoxicity of Titanium Dioxide Nanoparticles and Exploring the Protective Role of Holy Basil Oil Nanoemulsions in Rats.

This study was designed to evaluate the oxidative damage, genotoxicity, and DNA damage in the liver of rats treated with titanium nanoparticles (TiO2-NPs) with an average size of 28.0 nm and ξ-potential of - 33.97 mV, and to estimate the protective role of holy basil essential oil nanoemulsion (HBEON). Six groups of Male Sprague-Dawley rats were treated orally for 3 weeks as follows: the control group, HBEO or HBEON-treated groups (5 mg/kg b.w), TiO2-NPs-treated group (50 mg/kg b.w), and the groups treated with TiO2-NPs plus HBEO or HBEON. Samples of blood and tissues were collected for different analyses. The results revealed that 55 compounds were identified in HBEO, and linalool and methyl chavicol were the major compounds (53.9%, 12.63%, respectively). HBEON were semi-round with the average size and ζ-potential of 120 ± 4.5 nm and - 28 ± 1.3 mV, respectively. TiO2-NP administration increased the serum biochemical indices, oxidative stress markers, serum cytokines, DNA fragmentation, and DNA breakages; decreased the antioxidant enzymes; and induced histological alterations in the liver. Co-administration of TiO2-NPs plus HBEO or HBEON improved all the tested parameters and the liver histology, and HBEON was more effective than HBEO. Therefore, HEBON is a promising candidate able to protect against oxidative damage, disturbances in biochemical markers, gene expression, DNA damage, and histological changes resulting from exposure to TiO2-NPs and may be applicable in the food and pharmaceutical sectors.

Improvement of the antioxidant activity of thyme essential oil against biosynthesized titanium dioxide nanoparticles-induced oxidative stress, DNA damage, and disturbances in gene expression in vivo.

BACKGROUND: Titanium dioxide nanoparticles (TiO2-NPs) are widely utilized in medicine and industry; however, their safety in biological organisms is still unclear. In this study, we determined the bioactive constitutes of thyme essential oil (TEO) and utilized the nanoemulsion technique to improve its protective efficiency against oxidative stress, genotoxicity, and DNA damage of biosynthesized titanium dioxide nanoparticles (TiO2-NPs). METHODS: TEO nanoemulsion (TEON) was prepared using whey protein isolate (WPI). Sixty male Sprague-Dawley rats were divided into six groups and treated orally for 21 days including the control group, TEO, or TEON- treated groups (5 mg/kg b.w), TiO2-NPs-treated group (50 mg/kg b.w) and the groups received TiO2-NPs plus TEO or TEON. Blood and tissues samples were collected for different assays. RESULTS: The GC-MS analysis identified 17 bioactive compounds in TEO and thymol and carvacrol were the major compounds. TEON was irregular with average particles size of 230 ± 3.7 nm and ζ-potential of -24.17 mV. However, TiO2-NPs showed a polygonal shape with an average size of 50 ± 2.4 nm and ζ-potential of -30.44 mV. Animals that received TiO2-NPs showed severe disturbances in liver and kidney indices, lipid profile, oxidant/antioxidant indices, inflammatory cytokines, gene expressions, increased DNA damage, and pathological changes in hepatic tissue. Both TEO and TEON showed potential protection against these hazards and TEON was more effective than TEO. CONCLUSION: The nanoemulsion of TEO enhances the oil bioactivity, improves its antioxidant characteristics, and protects against oxidative damage and genotoxicity of TiO2-NPs.

Osteoarthritis complications and the recent therapeutic approaches.

The accelerated prevalence of osteoarthritis (OA) disease worldwide and the lack of convenient management led to the frequent search for unprecedented and specific treatment approaches. OA patients usually suffer from many annoying complications that negatively influence their quality of life, especially in the elderly. Articular erosions may lead eventually to the loss of joint function as a whole which occurs over time according to the risk factors presented in each case and the grade of the disease. Conventional therapies are advancing, showing most appropriate results but still greatly associated with many adverse effects and have restricted curative actions as well. Hence, novel management tools are usually required. In this review, we summarized the recent approaches in OA treatment and the role of natural products, dietary supplements and nanogold application in OA treatment to provide new research tracks for more therapeutic opportunities to those who are in care in this field.

Biosynthesis of gold nanoparticles for the treatment of osteoarthritis alone or in combination with Diacerein® in a rat model.

Gold (Au) compounds were used as an effective therapeutic agent for various inflammatory diseases; however, the use of Au compounds becomes limited because of its association with several side effects. Hence, gold nanoparticles (AuNPs) were developed as a new option for the medical proposes. However, the safety evaluation of gold nanoparticles (AuNPs) in osteoarthritis (OA) treatment remains vague. This study aimed to biosynthesize, characterize and evaluate the therapeutic effects of biosynthesized AuNPs and/or Diacerein® (DIA) in experimental OA. OA was induced by a single injection of monosodium iodoacetate (3 mg/joint) in the intra-articular knee of female rats. Normal rats (N-rats) and OA-rats were treated orally for 5 weeks as follow: untreated N-rats; untreated OA-rats; N-rats received DIA (50 mg/kg b.w); N-rats received AuNPs (30 µg/kg b.w.); N-rats received AuNPs plus DIA; OA-rats received DIA; OA-rats received AuNPs, and OA-rats received AuNPs plus DIA. Blood, knee cartilage, liver and kidney samples were collected for biochemical and histological analysis. The synthesized AuNPs were nearly spherical with average size of 20 nm and zeta potential of 33 mV. AuNPs and DIA induced a significant improvement in serum inflammatory cytokines, biochemical parameters, estrogen level, hepatic and renal oxidative markers, hepatic DNA fragmentation, genomic template stability and cartilage joint histology of OA-rats. AuNPs were more effective than DIA and the combined treatment was more effective than the single treatment. It could be concluded that AuNPs are promising for the treatment of OA alone or in combination with DIA.

Encapsulation of cinnamon oil in whey protein counteracts the disturbances in biochemical parameters, gene expression, and histological picture of the liver and pancreas of diabetic rats.

This study aimed to evaluate the protective role of encapsulated cinnamon oil emulsion (COE) in whey protein concentrate (WPC) against the disturbance in lipid profile, oxidative stress markers, and gene expression in streptozotocin (STZ)-treated rats. COE was analyzed using GC-MS, and the emulsion was prepared and characterized. In the in vivo study, six groups of male rats were treated orally for 4 weeks, including the control group, the group treated with STZ (D-rats), the groups received a low or high dose of COE (200 or 400 mg/kg B.w.), and the D-rats groups received COE at the low or high dose. Blood and tissue samples were collected after the end of the treatment period for biochemical, genetical, and histological analyses. The GC-MS results revealed that the major components of the oil were cinnamaldehyde, 1,8 cineole, acetic acid, 1,7,7-trimethylbicyclo[2.2.1]hept2yl ester, α-Pinene, and α-Terpineol. The size, zeta potential, and polydispersity index (PDI) of COE were 240 ± 1.03 nm, - 7.09 ± 0.42, and 0.36, respectively. The in vivo results revealed that COE at the two tested doses improved the levels of glucose, insulin, amylase, lipid profile, hepatic MDA, SOD, and GSH. COE also downregulated hepatic GLU2, FAS, SREBP-1c, and PEPCK gene expression and upregulated IGF-1 mRNA expression in diabetic rats in a dose-dependent manner. Moreover, COE improved and the histological picture of the liver and pancreas. It could be concluded that COE overcomes the disturbances in biochemical, cytological, and histopathological changes in D-rats via the enhancement of antioxidant capacity; reduces the oxidative stress; modulates the concerned gene expression; and may be promising to develop new drugs for diabetic treatment.