The Behavioral and Neurochemical Changes Induced by Boldenone and/or Tramadol in Adult Male Rats.

Boldenone and tramadol are abused among large sectors of adolescents. Therefore, the behavioral changes concerned with memory and cognitive functions and neurochemical variations were investigated in the cortex of rats treated with boldenone and/or tramadol. Rats were divided into control and rats treated with boldenone, tramadol, or both drugs. At the end of the treatment period, the memory and cognitive functions were evaluated by the Y-maze test (YMT) and elevated plus maze test (EPMT) and the motor activity was determined by the open field test (OFT). The cortex was dissected to carry out the neurochemical analyses. Rats treated with boldenone and/or tramadol showed impaired memory and cognitive functions and reduced motor activity. A significant increase in lipid peroxidation (MDA), nitric oxide (NO), and a significant decrease in reduced glutathione (GSH) were observed in the cortex of rats treated with boldenone and/or tramadol. The levels of acetylcholinesterase (AChE) and monoamine oxidase (MAO) decreased significantly. Western blot data showed a significant decrease in Bcl2 and a significant increase in caspase-3 and inducible nitric oxide synthase (iNOS) in rats treated with boldenone and/or tramadol. These changes were associated with neuronal death as indicated from the histopathological examination.The present findings indicate that boldenone and/or tramadol induced impairment in memory and cognitive functions. These changes could be mediated by the increase in oxidative stress, neuroinflammation, reduced AChE level, and reduced number of survived neurons in the cortex as indicated from the decreased Bcl2 level and the histological examination.

Transcranial photobiomodulation ameliorates midbrain and striatum neurochemical impairments and behavioral deficits in reserpine-induced parkinsonism in rats.

Photobiomodulation (PBM) of deep brain structures through transcranial infrared irradiation might be an effective treatment for Parkinson's disease (PD). However, the mechanisms underlying this intervention should be elucidated to optimize the therapeutic outcome and maximize therapeutic efficacy. The present study aimed at investigating the oxidative stress-related parameters of malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) and the enzymatic activities of sodium-potassium-ATPase (Na+, K+-ATPase), Acetylcholinesterase (AChE), and monoamine oxidase (MAO) and monoamine levels (dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the midbrain and striatum of reserpine-induced PD in an animal model treated with PBM. Furthermore, the locomotor behavior of the animals has been determined by the open field test. Animals were divided into three groups; the control group, the PD-induced model group, and the PD-induced model treated with the PBM group. Non-invasive treatment of animals for 14 days with 100 mW, 830 nm laser has demonstrated successful attainment in the recovery of oxidative stress, and enzymatic activities impairments induced by reserpine (0.2 mg/kg) in both midbrain and striatum of adult male Wistar rats. PBM also improved the decrease in DA, NE, and 5-HT in the investigated brain regions. On a behavioral level, animals showed improvement in their locomotion activity. These findings have shed more light on some mechanisms underlying the treatment potential of PBM and displayed the safety, easiness, and efficacy of PBM treatment as an alternative to pharmacological treatment for PD.

Evaluation of the therapeutic potential of cerebrolysin and/or lithium in the male Wistar rat model of Parkinson's disease induced by reserpine.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide and represents a challenge for clinicians. The present study aims to investigate the effects of cerebrolysin and/or lithium on the behavioral, neurochemical and histopathological alterations induced by reserpine as a model of PD. The rats were divided into control and reserpine-induced PD model groups. The model animals were further divided into four subgroups: rat PD model, rat PD model treated with cerebrolysin, rat PD model treated with lithium and rat PD model treated with a combination of cerebrolysin and lithium. Treatment with cerebrolysin and/or lithium ameliorated most of the alterations in oxidative stress parameters, acetylcholinesterase and monoamines in the striatum and midbrain of reserpine-induced PD model. It also ameliorated the changes in nuclear factor-kappa and improved the histopathological picture induced by reserpine. It could be suggested that cerebrolysin and/or lithium showed promising therapeutic potential against the variations induced in the reserpine model of PD. However, the ameliorating effects of lithium on the neurochemical, histopathological and behavioral alterations induced by reserpine were more prominent than those of cerebrolysin alone or combined with lithium. It can be concluded that the antioxidant and anti-inflammatory effects of both drugs played a significant role in their therapeutic potency.

The Neuroprotective Effect of α-Lipoic Acid and/or Metformin against the Behavioral and Neurochemical Changes Induced by Hypothyroidism in Rat.

OBJECTIVE: The present study evaluates the neuroprotective effect of α-lipoic acid (ALA) and/or metformin (MET) on the behavioral and neurochemical changes induced by hypothyroidism. METHODS: Rats were divided into control, rat model of hypothyroidism induced by propylthiouracil, and rat model of hypothyroidism treated with ALA, MET, or their combination. RESULTS: Behaviorally, hypothyroid rats revealed impaired memory and reduced motor activity as indicated from the novel object recognition test and open-field test, respectively. Hypothyroidism induced a significant increase in lipid peroxidation (malondialdehyde [MDA]) and a significant decrease in reduced glutathione (GSH) and nitric oxide (NO) in the cortex and hippocampus. These were associated with a significant increase in tumor necrosis factor-α (TNF-α) and a significant decrease in brain-derived neurotrophic factor (BDNF). Hypothyroidism decreased significantly the levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) and reduced the activities of acetylcholinesterase (AchE) and Na+, K+-ATPase in the cortex and hippocampus. Treatment of hypothyroid rats with ALA and/or MET showed an improvement in memory function and motor activity. Moreover, ALA and/or MET prevented the increase in MDA and TNF-α, and the decline in GSH, NO, BDNF, 5-HT, NE, and DA. It also restored AchE and Na+, K+-ATPase activities in the studied brain regions. CONCLUSION: ALA and/or MET has a potential neuroprotective effect against the adverse behavioral and neurochemical changes induced by hypothyroidism in rats.

Effect of curcumin nanoparticles on streptozotocin-induced male Wistar rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that afflicts millions of people all over the world. Intracerebroventricular (ICV) injection of a sub-diabetogenic dose of streptozotocin (STZ) was established as an experimental animal model of AD. The present study was conducted to evaluate the efficacy of curcumin nanoparticles (CNs) against the behavioral, neurochemical and histopathological alterations induced by ICV-STZ. The animals were divided into: control animals, the animal model of AD that received a single bilateral ICV microinjection of STZ, and the animals protected by a daily oral administration of CNs for 6 days before the ICV-STZ injection. The animals of all groups were subjected to surgical operation on the 7th day of administration. Then the administration of distilled water or CNs was continued for 8 days. The ICV-STZ microinjection produced cognitive impairment as evident from the behavioral Morris water maze (MWM) test and induced oxidative stress in the cortex and hippocampus as indicated by the significant increases in lipid peroxidation and nitric oxide (NO) levels and the significant decrease in reduced glutathione (GSH) levels. It also produced a significant increase in acetylcholinesterase (AChE) and tumor necrosis-alpha (TNF-ɑ) and a significant decrease in Na+,K + -ATPase. In addition, a significant increase in amino acid neurotransmitters occurred in the hippocampus, whereas a significant decrease was obtained in the cortex of STZ-induced AD rats. CNs ameliorated the behavioral, immunohistochemical and most of the neurochemical alterations induced by STZ in the hippocampus and cortex. It may be concluded that CNs might be considered as a promising therapeutic agent for the treatment of AD.

Antidepressant and antioxidant effects of transcranial irradiation with 830-nm low-power laser in an animal model of depression.

The present study aimed at investigating the antidepressant and antioxidant actions of near-infrared (NIR) laser at a wavelength of 830 nm and power of 100 mW which applied transcranially on an animal model of depression induced by repeated doses of reserpine (0.2 mg/kg). Thirty male Wistar adult rats were divided into three groups: rat model of depression; rat model of depression irradiated with laser for 14 days after induction of depression; and the control group that was given the drug vehicle and sham-exposed to the laser. Forced swimming test (FST) was used to verify the induction of animal model of depression and to screen the effect of antidepressant effect of low-level laser at the end of the experiment. Monoamine level, oxidative stress markers, and activities of acetylcholinesterase (AchE) and monoamine oxidase (MAO) were determined in the cortex and hippocampus of the rat brain. Reserpine resulted in depletion of monoamines and elevation in the oxidative stress markers and change in the enzymatic activities measured in both brain areas. Laser irradiation has an inhibitory action on the monoamine oxidase (MAO) in the cortex and hippocampus leading to elevation of the monoamine levels and attenuation of the oxidative stress in the studied areas. FST has emphasized the antidepressant effect of the utilized laser irradiation parameters on the behavioral level. The present findings provide evidence for the antidepressant and antioxidant actions of NIR low-power laser in the rat model of depression. Accordingly, low-laser irradiation may be presented as a potential candidate modality for depression treatment.

Evaluation of antioxidant and anti-inflammatory efficacy of caffeine in rat model of neurotoxicity.

Objective: The present study aims to investigate the neuroprotective effect of caffeine against aluminum chloride (AlCl3)-induced neurotoxicity in rats. Methods: Twenty-one male albino rats were divided into 3 groups: control, AlCl3-intoxicated group that received daily oral administration of AlCl3 (100 mg/kg for 30 days) and protected group injected daily with caffeine (20 mg/kg intraperitoneally) one hour before oral administration of AlCl3 for 30 days. Levels of lipid peroxidation, reduced glutathione, and nitric oxide and the activities of acetylcholinesterase (AchE) and Na+/K+-ATPase were measured spectrophotometrically. Tumor necrosis factor-α (TNF-α) was evaluated by ELISA kit. Results: The data revealed evidence of oxidative and nitrosative stress in the cerebral cortex, hippocampus, and striatum of AlCl3-intoxicated rats. This was indicated from the increased levels of lipid peroxidation and nitric oxide together with the decreased level of reduced glutathione. Moreover, the daily AlCl3 administration increased AchE and Na+/K+-ATPase activities and the level of TNF-α in the selected brain regions. Protection with caffeine ameliorated the oxidative stress induced by AlCl3 in the cerebral cortex, hippocampus, and striatum. In addition, caffeine restored the elevated level of TNF-α in the hippocampus and striatum. This was accompanied by an improvement in the activities of AchE and Na+/K+-ATPase in the studied brain regions. Discussion and conclusions: The present findings clearly indicate that caffeine provides a significant neuroprotection against AlCl3-induced neurotoxicity mediated by its antioxidant, anti-inflammatory, and anticholinesterase properties.

Effect of curcumin nanoparticles on the cisplatin-induced neurotoxicity in rat.

The present study is conducted to evaluate the neuroprotective effect of curcumin nanoparticles (CUR NP) against the neurotoxicity induced by cisplatin (CP) in rat. Rats were divided into control group that received saline solution, CP-treated rats that received a single i.p. injection of CP (12 mg/kg body wt), and CP-treated rats that received a single i.p injection of CP (12 mg/kg body wt) followed by a daily oral administration of CUR NP (50 mg/kg body wt) for 14 days. At the end of the experiment, the motor activity of rats was evaluated by open field test. The neurochemical and histopathological changes were investigated in the cerebral cortex. A significant decrease in motor activity was observed in CP-treated rats. This was associated with a significant increase in the cortical levels of lipid peroxidation, nitric oxide, tumor necrosis factor-α, caspase-3, and acetylcholinesterase activity. However, CP induced a significant decrease in reduced glutathione levels and Na+, K+-ATPase activity. In rats treated with CP and CUR NP, no significant changes were recorded in the parameters of the open field test as compared to control. In addition, treatment with CUR NP prevented all the neurochemical changes induced by CP except the increased value of nitric oxide. CUR NP also reduced the histopathological changes induced by CP. It is clear from the present data that CUR NP could ameliorate the neurotoxic effect induced by cisplatin.

Protection by Neostigmine and Atropine Against Brain and Liver Injury Induced by Acute Malathion Exposure.

We examined the effect of treatment with neostigmine alone or with atropine on brain oxidative stress and on brain and liver tissue damage following acute malathion toxicity. Rats were intraperitoneally treated with malathion 150 mg/kg along with neostigmine (200 or 400 µg/kg) or neostigmine (200 µg/kg) + atropine (1 mg/kg) and euthanized 4 h later. Results indicated that compared with the saline group, malathion resulted in (i) higher brain malondialdehyde (MDA) and nitric oxide (46.4% and 86.2%); (ii) decreased brain reduced glutathione (GSH) (67.6%); (iii) decreased brain paraoxonase-1 (PON1), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (31.2%, 21.6% and 60%); (iv) decreased brain glucose (-38.1%); (v) neuronal degeneration in cortex and hippocampus and markedly increased glial fibrillary acidic protein (GFAP) immunostaining in the hippocampus; (v) hydropic and fatty degeneration in liver. Rats treated with malathion along with neostigmine or neostigmine + atropine showed no change in brain MDA but decreased nitric oxide (-34.2%-48%). GSH increased after neostigmine 200 µg/kg or neostigmine + atropine (35.8% and 41%). PON1 activity increased (42%-35.2%) and glucose concentrations increased (91.5%-81.5%) by 400 µg/kg neostigmine or neostigmine + atropine. Brain AChE activity remained unchanged but BChE activity showed 18.3% increment after 400 µg/kg neostigmine. Rats treated with 400 µg/kg neostigmine or neostigmine + atropine had normal neuronal appearance in cortex and hippocampus and weak GFAP expression in hippocampus. Liver damage was prevented by neostigmine + atropine. These results suggest that treatment with neostigmine + atropine afforded protection against the deleterious effects of acute malathion on the brain and liver.

The chronic effect of pulsed 1800 MHz electromagnetic radiation on amino acid neurotransmitters in three different areas of juvenile and young adult rat brain.

The extensive use of mobile phones worldwide has raised increasing concerns about the effects of electromagnetic radiation (EMR) on the brain due to the proximity of the mobile phone to the head and the appearance of several adverse neurological effects after mobile phone use. It has been hypothesized that the EMR-induced neurological effects may be mediated by amino acid neurotransmitters. Thus, the present study investigated the effect of EMR (frequency 1800 MHz, specific absorption rate 0.843 W/kg, power density 0.02 mW/cm2, modulated at 217 Hz) on the concentrations of amino acid neurotransmitters (glutamic acid, aspartic acid, gamma aminobutyric acid, glycine, taurine, and the amide glutamine) in the hippocampus, striatum, and hypothalamus of juvenile and young adult rats. The juvenile and young adult animals were each divided into two groups: control rats and rats exposed to EMR 1 h daily for 1, 2, and 4 months. A subgroup of rats were exposed daily to EMR for 4 months and then left without exposure for 1 month to study the recovery from EMR exposure. Amino acid neurotransmitters were measured in the hippocampus, striatum, and hypothalamus using high-performance liquid chromatography. Exposure to EMR induced significant changes in amino acid neurotransmitters in the studied brain areas of juvenile and young adult rats, being more prominent in juvenile animals. It could be concluded that the alterations in amino acid neurotransmitters induced by EMR exposure of juvenile and young adult rats may underlie many of the neurological effects reported after EMR exposure including cognitive and memory impairment and sleep disorders. Some of these effects may persist for some time after stopping exposure.

Cerebellar neurochemical and histopathological changes in rat model of Parkinson's disease induced by intrastriatal injection of rotenone.

The aim of the present work was to investigate the neurochemical changes induced in the cerebellum of rat model of Parkinson's disease (PD). Rats were divided into two groups; control and rat model of PD induced by the intrastriatal injection of rotenone. As compared to control, a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine were observed in the cerebellum of rat model of PD. This was associated with a significant increase in lipid peroxidation, nitric oxide and tumor necrosis factor-α and a significant decrease in reduced glutathione. A significant decrease in acetylcholinesterase and a significant increase in Na+,K+-ATPase were recorded in the cerebellum of rat model of PD. In addition the cerebellar sections from rat model of PD showed marked necrosis of Purkinje cells, irregular damaged cells, cytoplasmic shrinkage, necrosis and perineuronal vacuolation. The present results indicate that the disturbance in the balance between the excitatory and inhibitory amino acids may have a role in the pathogenesis of PD. According to the present neurochemical and histopathological changes, the cerebellum should be taken into consideration during the treatment of PD.

Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect.

Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1ß, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone.

Neurochemical impact of bisphenol A in the hippocampus and cortex of adult male albino rats.

Bisphenol A (BPA), an endocrine-disrupting chemical, is widely used in the manufacture of polycarbonated plastics and epoxy resins and line metal beverage cans. Growing evidence suggests that BPA acts directly on neuronal functions as it is lipophilic and could accumulate in the brain. The present study aims to investigate the effect of two doses of BPA (10 mg/kg for 6 and 10 weeks and 25 mg/kg for 6 weeks) on excitatory (glutamate and aspartate) and inhibitory (γ-aminobutyric acid, glycine, and taurine) amino acid neurotransmitter levels in the cortex and hippocampus. This study extends to investigate the effect of BPA on acetylcholinesterase (AchE) activity and some oxidative stress parameters in the two regions. In the cortex, a significant increase in the excitatory and a significant decrease in the inhibitory amino acids occurred after BPA (10 mg/kg for 10 weeks and 25 mg/kg for 6 weeks). This was accompanied by a significant increase in lipid peroxidation, nitric oxide, and reduced glutathione after 6 weeks of BPA (25 mg/kg). In the hippocampus, a significant increase in the excitatory and inhibitory amino acid neurotransmitters occurred after 6 weeks of BPA. Hippocampal lipid peroxidation increased significantly after BPA exposure and hippocampal reduced glutathione increased significantly after 6 weeks of BPA exposure (10 mg/kg). BPA induced a significant increase in cortical and hippocampal AchE activity. The present neurochemical changes in the cortex and hippocampus suggest that BPA induced a state of excitotoxicity and oxidative stress. This may raise concerns about the exposure of humans to BPA due to its wide applications in industry.

Effect of caffeine-chitosan nanoparticles and α-lipoic acid on the cardiovascular changes induced in rat model of obesity.

The current research aims to study the therapeutic efficacy of alpha-lipoic acid (α-LA) and caffeine-loaded chitosan nanoparticles (Caf-CNs) against cardiovascular complications induced by obesity. Rats were divided randomly into: control, high fat diet (HFD) induced obesity rat model, obese rats treated with α-LA and/or Caf-CNs. Triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) as well as activities of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) significantly increased in the serum of obese rats. In addition, plasma atherogenic index, atherogenic coefficient and Castelli's risk indices I and II showed a significant increase. Additionally, levels of malondialdehyde (MDA) and nitric oxide (NO) and activity of monoamine oxidase (MAO) were significantly elevated in heart tissues of obese rats. However, cardiac Na+/K+-ATPase and acetylcholinesterase (AchE) activities and reduced glutathione (GSH), serotonin (5-HT), norepinephrine (NE) and dopamine (DA) as well as serum high-density lipoprotein cholesterol (HDL-C) were significantly reduced in obese rats. Treatment with α-LA and/or Caf-CNs ameliorated almost all the biochemical and histopathological alterations caused by obesity. In conclusion, the present data revealed that α-LA and/or Caf-CNs may be an effective therapeutic approach against cardiac complications caused by obesity through their antilipemic, anti-atherogenic, antioxidant, and anti-inflammatory activities.

Cerebrolysin potentiates the antidepressant effect of lithium in a rat model of depression.

RATIONALE: Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants. OBJECTIVES: The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. METHODS: The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. RESULTS: Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. CONCLUSIONS: The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment.

The anticonvulant effect of cooling in comparison to α-lipoic acid: a neurochemical study.

Brain cooling has pronounced effects on seizures and epileptic activity. The aim of the present study is to evaluate the anticonvulsant effect of brain cooling on the oxidative stress and changes in Na(+), K(+)-ATPase and acetylcholinesterase (AchE) activities during status epilepticus induced by pilocarpine in the hippocampus of adult male rat in comparison with α-lipoic acid. Rats were divided into four groups: control, rats treated with pilocarpine for induction of status epilepticus, rats treated for 3 consecutive days with α-lipoic acid before pilocarpine and rats subjected to whole body cooling for 30 min before pilocarpine. The present findings indicated that pilocarine-induced status epilepticus was accompanied by a state of oxidative stress as clear from the significant increase in lipid peroxidation (MDA) and superoxide dismutase (SOD) and significant decrease in reduced glutathione and nitric oxide (NO) levels and the activities of catalase, AchE and Na(+), K(+)-ATPase. Pretreatment with α-lipoic acid ameliorated the state of oxidative stress and restored AchE to nearly control activity. However, Na(+), K(+)-ATPase activity showed a significant decrease. Rats exposed to cooling for 30 min before the induction of status epilepticus revealed significant increases in MDA and NO levels and SOD activity. AchE returned to control value while the significant decrease in Na(+), K(+)-ATPase persisted. The present data suggest that cooling may have an anticonvulsant effect which may be mediated by the elevated NO level. However, brain cooling may have drastic unwanted insults such as oxidative stress and the decrease in Na(+), K(+)-ATPase activity.

Effect of alpha-lipoic acid and caffeine-loaded chitosan nanoparticles on obesity and its complications in liver and kidney in rats.

The present work investigated the effect of α-lipoic acid (ALA) and caffeine-loaded chitosan nanoparticles (CAF-CS NPs) on obesity and its hepatic and renal complications in rats. Rats were divided into control, rat model of obesity induced by high fat diet (HFD), and obese rats treated with ALA and/or CAF-CS NPs. At the end of the experiment, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and the levels of urea, creatinine, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were determined in the sera of animals. In addition, malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were measured in hepatic and renal tissues. Renal Na+, K+-ATPase was assessed. The histopathological changes were examined in the hepatic and renal tissues. Obese rats showed a significant increase in AST, ALT, ALP, urea, and creatinine. This was associated with a significant increase in IL-1ß, TNF-α, MDA, and NO. A significant decrease in hepatic and renal GSH and renal Na+, K+-ATPase activity was recorded in obese rats. Obese rats also showed histopathological alterations in hepatic and renal tissues. Treatment with ALA and/or CAF-CS NPs reduced the weight of obese rats and ameliorated almost all the hepatic and renal biochemical and histopathological changes induced in obese rats. In conclusion, the present findings indicate that ALA and/or CAF-CS NPs offered an effective therapy against obesity induced by HFD and its hepatic and renal complications. The therapeutic effect of ALA and CAF-CS NPs could be mediated through their antioxidant and anti-inflammatory properties.

Evaluation of the Therapeutic Effect of Curcumin-Conjugated Zinc Oxide Nanoparticles on Reserpine-Induced Depression in Wistar Rats.

Depression, a devastating brain illness, necessitates the exploration of novel antidepressant treatments. We evaluated the antidepressant effects of free curcumin, zinc oxide nanoparticles (ZnO NPs), and curcumin-conjugated zinc oxide nanoparticles (Zn(cur)O NPs). The nanoformulations were extensively characterized using advanced techniques. An acute toxicity study ensured the safety of Zn(cur)O NPs. Rats were assigned to one of five groups: control, reserpine-induced depression model, treatment with ZnO NPs, free curcumin, or Zn(cur)O NPs. Behavioral assessments (forced swimming test [FST] and open-field test [OFT]) and neurochemical analyses were conducted. Zn(cur)O NPs exhibited superior efficacy in ameliorating reserpine-induced behavioral and neurochemical effects compared to free curcumin and ZnO NPs. The reserpine-induced model displayed reduced motor activity, swimming time, and increased immobility time in the FST and OFT. Treatment with Zn(cur)O NPs 45 mg/kg significantly improved motor activity and reduced immobility time. Furthermore, Zn(cur)O NPs decreased malondialdehyde (MDA) levels while increasing reduced glutathione (GSH) and catalase (CAT) levels. Additionally, concentrations of serotonin (5-HT) and norepinephrine (NE) increased. In conclusion, curcumin-conjugated zinc oxide nanoparticles demonstrate potent antidepressant effects, alleviating depressive-like behavior in rats. These findings support Zn(cur)O NPs as a promising therapeutic strategy for depression management, warranting further investigation and clinical validation.

Mesenchymal Stem Cells and Begacestat Mitigate Amyloid-ß 25-35-Induced Cognitive Decline in Rat Dams and Hippocampal Deteriorations in Offspring.

Alzheimer's disease (AD) is the most common cause of age-related neurodegeneration and cognitive decline. AD more commonly occurs in females than in males, so it is necessary to consider new treatments specifically targeting this population. The present study investigated the protective effects of Begacestat (γ-secretase inhibitor-953, GSI-953) and bone marrow-derived mesenchymal stem cells (BM-MSCs) during pregnancy on cognitive impairment in rat dams and neurodegeneration in offspring caused by the intracerebroventricular injection of Aß 25-35 before pregnancy. The performances of dams injected with amyloid-ß 25-35 (Aß 25-35) during behavioral tests were significantly impaired. The offspring of Aß 25-35-injected dams treated with BM-MSCs or GSI-953 showed a dramatically reduced number and size of activated microglial cells, enhancement in the processes length, and a decrease in the proinflammatory cytokine levels. Additionally, BM-MSC or GSI-953 therapy reduced Aß 25-35-induced increases in tau phosphorylation and amyloid precursor protein levels in the neonates' hippocampus and elevated the lower levels of glycogen synthase kinase-3 and brain-derived neurotrophic factor; moreover, reversed Aß 25-35-induced alterations in gene expression in the neonatal hippocampus. Finally, the treatments with BM-MSC or GSI-953 are globally beneficial against Aß 25-35-induced brain alterations, particularly by suppressing neural inflammation, inhibiting microglial cell activation, restoring developmental plasticity, and increasing neurotrophic signaling.

Bone Marrow-Derived Mesenchymal Stem Cells and γ-Secretase Inhibitor Treatments Suppress Amyloid-ß25-35-Induced Cognitive Impairment in Rat Dams and Cortical Degeneration in Offspring.

Alzheimer's disease (AD) is the most frequent cause of age-related neurodegeneration and ensuing cognitive impairment. Progressive deposition of extracellular amyloid beta (Aß) aggregates (plaques) and intracellular hyperphosphorylated Tau protein (p-Tau) are the core pathological markers of AD but may precede clinical symptoms by many years, presenting a therapeutic window of opportunity. Females are more frequently afflicted by AD than males, necessitating evaluation of novel treatments for the female population. The current study examined the protective efficacies of intravenous bone marrow-derived mesenchymal stem cells (BM-MSCs) and oral gamma-secretase inhibitor-953 (GSI-953) during pregnancy on cognitive impairment in rat dams and neurodegeneration in offspring induced by intracerebroventricular injection of Aß25-35 prior to pregnancy. The Aß25-35 (AD) group exhibited significant (P < 0.001) impairments in the Y-maze and novel object recognition test performance prior to conception. Histological analysis of the offspring cortex revealed substantial dendritic shrinkage and activation of microglial cells, while neurochemical analysis demonstrated significant increases in the proinflammatory cytokine interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). In contrast, BM-MSC or GSI-953 treatment of dams following Aß25-35 injection significantly (P < 0.001) reduced the number and size of activated microglial cells, markedly increased dendrite length, and reversed proinflammatory cytokine elevations in offspring. Moreover, BM-MSC or GSI-953 treatment reversed the Aß25-35-induced amyloid precursor protein and p-Tau elevations in the offspring brain; these changes were accompanied by upregulation of the brain-derived neurotrophic factor and downregulation of glycogen synthase kinase-3ß in the serum and brain. Treatment with BM-MSCs or GSI-953 also reversed Aß25-35-induced elevations in different gene expressions in the neonatal cortex. Finally, treatment of dams with BM-MSCs or GSI-953 prevented the Aß25-35-induced disruption of newborn brain development. Thus, BM-MSC and GSI-953 treatments have broad-spectrum effects against Aß25-35-induced brain pathology, including the suppression of neural inflammation, restoration of developmental plasticity, and promotion of neurotrophic signaling.