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.

Therapeutic Effects of Alpha Lipoic Acid and/or Caffeine-Loaded Chitosan Nanoparticles on Memory Impairment and Neurochemical Changes in High-Fat Diet-Induced Obese Rats.

The therapeutic effects of alpha lipoic acid (LA) and/or caffeine-loaded chitosan nanoparticles (CCNPs) on obesity-induced memory impairment were evaluated in the present study. Rats were divided into control rats, obese rats induced by high fat diet (HFD) and obese rats treated with LA and/or CCNPs. Obesity was confirmed by measuring the body mass index (BMI). Memory and cognitive functions were evaluated by novel object recognition test (NORT). The levels of serotonin (5-HT), dopamine (DA), norepinephrine (NE), lipid peroxidation (MDA), nitric oxide (NO), reduced glutathione (GSH), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), leptin (LEP) and ghrelin (GHR) and the activities of monoamine oxidase (MAO), acetylcholinesterase (AchE) and Na+,K+,ATPase were determined in the cortex and hippocampus. The cerebral histopathological alterations were examined in obese rats. Obese rats showed impaired memory and exhibited significant neurochemical changes, including decreased levels of 5-HT, DA, GSH, GHR, and Na+,K+-ATPase activity, as well as an increase in AchE, MAO, MDA, NO, IL-1ß, TNF-α, and LEP. LA and/or CCNPs treatment reduced BMI and improved memory. LA or CCNPs alleviated the cortical and hippocampal neurochemical changes and histopathological changes induced by obesity. Furthermore, LA and CCNPs exhibited antioxidant and anti-inflammatory properties, which likely contributed to their effects. However, no synergistic effect was observed between LA and CCNPs. These findings suggest that LA or CCNPs may be a potential therapy against obesity and its adverse effects on memory, mediated by their ability to restore monoamine levels and exhibit antioxidant and anti-inflammatory properties.

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.

Cardamom oil ameliorates behavioral and neuropathological disorders in a rat model of depression induced by reserpine.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is a public health problem. Despite the availability of treatment options, its prevalence is increasing. A high rate of treatment failure is often reported, along with considerable side effects associated with synthetic antidepressants. Therefore, developing effective and safe antidepressants from traditional herbs or natural products as an alternative strategy is warranted to avoid side effects and increase drug efficacy. In traditional medicine, cardamom has traditionally been used to treat conditions like asthma, tooth and gum infections, cataracts, nausea, diarrhea, and even depression and anxiety as well as some problems with the heart, kidneys, and digestive system. AIM OF THE STUDY: The current study aimed to evaluate the antidepressant activity of cardamom oil in a rat model of depression induced by reserpine and compare it with the activity of the antidepressant drug fluoxetine. MATERIALS AND METHODS: Depression-like symptoms were induced in male rats by daily i. p. injection of reserpine (0.2 mg/kg/d for 15 d followed by 0.1 mg/kg/d for 21 d to maintain the depressive state), and the rats were treated with cardamom oil (oral dose = 200 mg/kg/d) for 21 d along with the maintenance dose of reserpine. We performed behavioral tests (forced swimming test and open-field test) and evaluated biochemical markers of depression. RESULTS: Our findings revealed that cardamom oil attenuated depression-like symptoms in reserpine-injected rats by improving the behavioral changes measured by the forced swimming test and the locomotor activities measured by the open-field test. In reserpine-injected rats, cardamom oil exerted antidepressant-like effects by modulating lower levels of brain monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), GSH, and higher oxido-nitrosative stress parameters (malondialdehyde and nitric oxide). Moreover, cardamom oil alleviated depression-like behaviors by lowering monoamine oxidase activity and raising the activities of Na+/K+-ATPase and acetylcholinesterase and levels of a brain-derived neurotrophic factor in the cortex and hippocampus. CONCLUSION: We recommend the use of cardamom oil as a safe and reliable treatment or an adjuvant for preventing depression-like symptoms in patients suffering from depression.

Sensitivity and specificity of microRNA-204, CA125, and CA19.9 as biomarkers for diagnosis of ovarian cancer.

BACKGROUND: Ovarian cancer is usually detected at later stages and no effective screening approach, has been identified. Therefore, sensitive and specific biomarkers for detecting ovarian cancer are urgently needed. OBJECTIVE: This study aimed to investigate the efficacy of six biomarkers for the early clinical diagnosis of ovarian cancer. SUBJECTS & METHODS: The study included 120 patients (benign ovarian tumors and early and late ovarian carcinoma) and 30 control healthy volunteers. MiRNA-204, CA125, CA19.9, hepcidin, microfibril-associated glycoprotein 2, and ferroportin levels were determined in all patients and control volunteers. RESULTS: The combined area under the receiver operating characteristic curves for miRNA-204, CA125, and CA19.9 were 0.938, 1.000, and 0.998 for benign tumors and early and late ovarian carcinomas, respectively. The sensitivities of miRNA-204, CA125, and CA19.9 were 98.04%, 100.00%, and 96.19% and the specificities were 58.33%, 62.50%, and 57.78%, respectively. CONCLUSION: The positive predictivity of miRNA-204, CA125, and CA19.9 for ovarian cancer is high (59.57%, 58.24%, and 61.67%, respectively). Thus, the combination of these three biomarkers is a good diagnostic tool for ovarian cancer.

Association of TRPV5, CASR, and CALCR genetic variants with kidney stone disease susceptibility in Egyptians through main effects and gene-gene interactions.

Kidney stone disease (KSD) represents an urgent medical problem because of increasing its prevalence. Several functional polymorphisms in genes involved in the renal handling of calcium were associated with KSD pathogenesis. Among those, the rs4236480 of transient receptor potential vanilloid member 5 (TRPV5) gene, the rs1801725 of calcium-sensing receptor (CASR) gene, and the rs1801197 of calcitonin receptor (CALCR) gene appear to be of great importance. Due to the scarce data on the Egyptians, this study aimed to evaluate the association of these candidate genetic variants with the risk of developing KSD in an Egyptian population. To do so, the biochemical parameters were measured along with the genotyping of the three polymorphisms using allelic discrimination assay in 134 KSD patients and 86 age and sex-matched healthy subjects. The results showed that the genotypic distributions and allelic frequencies of the studied variants were significantly different between cases and controls. The three polymorphisms increased the risk of KSD significantly under all the tested genetic models (OR ranges from 2.152 to 5.994), except for the recessive model of the CALCR rs1801197 polymorphism after Bonferroni correction. The gene-gene interaction analyzed by multifactor dimensionality reduction selected the three-locus combination as the best model associated with the susceptibility to KSD with OR 9.706. Further, synergistic interactions were identified between TRPV5 rs4236480 and CALCR rs1801197 variants and CASR rs1801725 and CALCR rs1801197 variants. In conclusion, the TRPV5 rs4236480, CASR rs1801725, and CALCR rs1801197 polymorphisms showed a significant association with the risk of KSD in the Egyptian population. Furthermore, their complex interactions might have an impact on the genetic susceptibility to develop KSD.

Neuroprotective Effect of Ashwagandha Extract against the Neurochemical Changes Induced in Rat Model of Hypothyroidism.

The current aim is to evaluate the effect of ashwagandha root extract (AE) on the neurochemical changes induced in the cortex and hippocampus as a consequence of thyroid dysfunction induced by propylthiouracil (PTU). Male Wistar rats were divided into; control, AE treated rats, rat model of hypothyroidism and rat model of hypothyroidism treated with either AE or L-thyroxine (T4) for 1 month. Rat model of hypothyroidism showed a significant decrease in serum levels of tri-iodothyronine (T3) and T4 and a significant increase in cortical and hippocampal lipid peroxidation (MDA), nitric oxide (NO), superoxide dismutase (SOD) and catalase (CAT). However, reduced glutathione (GSH) decreased significantly. This was associated with a significant increase in hippocampal tumor necrosis factor-α (TNF-α) and cortical dopamine levels. Both L-thyroxine and AE restored T3 and T4 levels. In the hippocampus L-Thyroxine prevented the increase in MDA and restored GSH but failed to restore the increased NO and TNF-α. In the cortex L-thyroxine didn't change the increased MDA and NO and the decreased GSH induced by PTU. L-thyroxine increased cortical and hippocampal SOD and CAT. AE prevented the increased hippocampal MDA, NO and TNF-α and the decreased GSH level induced by PTU. In the cortex AE failed to restore MDA and NO but prevented the decrease in GSH. The increase in cortical dopamine level induced by PTU was ameliorated by L-thyroxine and improved by AE. The present data indicate that AE could prevent thyroid dysfunction and reduce its complications on the nervous system including oxidative stress and neuroinflammation.

The Effect of Curcumin Nanoparticles on Cisplatin-Induced Cardiotoxicity in Male Wistar Albino Rats.

The cardiotoxicity of chemotherapeutic drugs as cisplatin has become a major issue in recent years. The present study investigates the efficacy of curcumin nanoparticles against the cardiotoxic effects of cisplatin by assessment of oxidative stress parameters, Na+,K+-ATPase, acetylcholinesterase (AchE) and tumor necrosis factor-alpha (TNF-α) in cardiac tissue in addition to serum lactate dehydrogenase (LDH). Rats were divided into three groups: control rats that received saline for 14 days; cisplatin-treated rats that received a single intraperitoneal (i.p.) injection of cisplatin (12 mg/kg) followed by a daily oral administration of saline (0.9%) for 14 days and rats treated with a single i.p. injection of cisplatin (12 mg/kg) followed by a daily oral administration of curcumin nanoparticles (50 mg/kg) for 14 days. Cisplatin resulted in a significant increase in lipid peroxidation, nitric oxide (NO), and TNF-α and a significant decrease in reduced glutathione (GSH) levels and Na+, K+- ATPase activity. Moreover, significant increases in cardiac AchE and serum lactate dehydrogenase activities were recorded. Treatment of cisplatin-injected animals with curcumin nanoparticles ameliorated all the alterations induced by cisplatin in the heart of rats. This suggests that curcumin nanoparticles can be used as an important therapeutic adjuvant in chemotherapeutic and other toxicities mediated by oxidative stress and inflammation.

Curcumin nanoparticles ameliorate hepatotoxicity and nephrotoxicity induced by cisplatin in rats.

The present work was conducted to investigate the effect of curcumin nanoparticles (CUR NPs) on cisplatin-induced hepatotoxicty and nephrotoxicity in rats. Rats were divided randomly into the following: control, rats treated daily with CUR NPs (50 mg/kg body wt/day) for 14 days, rats treated with a single dose of cisplatin (12 mg/kg body wt, i.p), and rats treated with a single dose of cisplatin followed by a daily administration of CUR NPs for 14 days. Cisplatin-induced hepato- and nephrotoxicity were evaluated by histological examinations and biochemical analyses of liver and kidney functions. Cisplatin induced significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and in the levels of bilirubin, urea, uric acid and creatinine. In addition, the levels of hepatic and renal lipid peroxidation (MDA), nitric oxide (NO), and serum tumor necrosis factor-α (TNF-α) increased significantly. However, cisplatin significantly decreased hepatic and renal reduced glutathione levels and renal Na+/K+-ATPase activity. Treatment with CUR NPs ameliorated almost all the biochemical changes induced by cisplatin and improved the histopathological alterations in liver and kidney. In conclusion, the present findings indicate that CUR NPs offered an effective protection against cisplatin-induced hepatotoxicity and nephrotoxicity through its antioxidant and anti-inflammatory properties.