The protective effects of chitosan and curcumin nanoparticles against the hydroxyapatite nanoparticles-induced neurotoxicity in rats.

Hydroxyapatite nanoparticles (HANPs) have extensive applications in biomedicine and tissue engineering. However, little information is known about their toxicity. Here, we aim to investigate the possible neurotoxicity of HANPs and the possible protective role of chitosan nanoparticles (CNPs) and curcumin nanoparticles (CUNPs) against this toxicity. In our study, HANPs significantly reduced the levels of neurotransmitters, including acetylcholine (Ach), dopamine (DA), serotonin (SER), epinephrine (EPI), and norepinephrine (NOR). HANPs significantly suppressed cortical expression of the genes controlling mitochondrial biogenesis such as peroxisome proliferator activator receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (mTFA). Our findings revealed significant neuroinflammation associated with elevated apoptosis, lipid peroxidation, oxidative DNA damage and nitric oxide levels with significant decline in the antioxidant enzymes activities and glutathione (GSH) levels in HANPs-exposed rats. Meanwhile, co-supplementation of HANP-rats with CNPs and/or CUNPs significantly showed improvement in levels of neurotransmitters, mitochondrial biogenesis, oxidative stress, DNA damage, and neuroinflammation. The co-supplementation with both CNPs and CUNPs was more effective to ameliorate HANPs-induced neurotoxicity than each one alone. So, CNPs and CUNPs could be promising protective agents for prevention of HANPs-induced neurotoxicity.

Ginseng, Tribulus Extracts and Pollen Grains Supplementation Improves Sexual State, Testes Redox Status, and Testicular Histology in Nile Tilapia Males.

This study aimed to investigate the effect of dietary supplementation of three natural antioxidants on sex hormone levels, enzymatic and non-enzymatic antioxidant systems, and histological changes in the testes of male Nile tilapia, Oreochromis niloticus. A total of 210 male Nile tilapia were distributed into seven treatments (three replicates for each) with an initial weight of 3.67 g fish-1. The fish were fed experimental diets (32% crude protein) without supplementation as control or supplemented with ginseng extract (GE; 0.2 and 0.4 g GE kg-1 diet), Tribulus terrestris extract (TT; 0.6 and 1.2 g TT kg-1 diet), and date palm pollen grains (DPPG; 3 and 6 g DPPG kg-1 diet) for 84 days. The results revealed a significant increase in the luteinizing hormone level with TT, DPPG, and GE supplementation increased the levels by 22.9%, 18.5%, and 17.6%, respectively. The testosterone level also increased significantly with TT1.2, GE0.4, TT0.6, and DPPG6 by 86.23%, 64.49%, 57.40%, and 24.62%, respectively. The antioxidant status in the testis homogenate showed a significant decrease in the level of thiobarbituric acid-reactive substances when using different dietary substances. In addition, glutathione reduced contents, glutathione S-transferases, glutathione peroxidase, catalase, and superoxide dismutase activities significantly increased with different dietary supplementation in a dose-dependent manner. The histological evaluation revealed normal histological features of the testes in all treatments with increasing active seminiferous tubules (%) in GE, TT, and DPPG supplemented groups, especially with the highest levels. In conclusion, the dietary supplementation of GE, TT, and DPPG enhanced sex hormones level, redox status, and testis structure and could improve the male reproductive performance of Nile tilapia.

Impact of ginseng on neurotoxicity induced by cisplatin in rats.

Over the years, many researches have shown the potential protective effects of ginseng for preventing and treating neurological damage and their related diseases. Neuronal disturbance is one of the most common serious effects of cisplatin chemotherapy that triggers memory impairment and cognitive disability. Based on the hypothesis that mechanistic pathways of ginseng against the neurological and biochemical disturbance remain unclear, therefore, this study was designed to investigate the neuroprotective effect of ginseng extract against neurological and behavior abnormality induced by cisplatin in male rats. Animals were divided into 4 groups. Group 1 served as a control, group 2 was orally administrated with ginseng (100 mg/kg BW) daily for 90 days, group 3 was injected intraperitoneally with cisplatin (4 mg/kg BW) once a week for 90 days, and group 4 received ginseng and cisplatin. Cisplatin induced a learning and memory dysfunction in the Morris water maze task and locomotor disability in the rotarod test. In addition, cisplatin disrupted the oxidant/antioxidant systems, neuroinflammatory molecules (TNF-α, IL-6, IL-12, and IL-1ß), neurotransmitters, and apoptotic (caspase-3, P53, and Bax) and dementia markers (amyloid-ß40 and amyloid-ß 42). Co-treatment with ginseng extracts successfully ameliorated the cognitive behaviors and intramuscular strength and presented a good protective agent against neurological damage. Histopathological and histochemical studies proved the neuroprotective effect of ginseng. Our data showed that ginseng capable to counteract the memory dysfunction is induced by cisplatin via reducing oxidative stress and neuroinflammation restoring the neurological efficiency.

Scavenging Properties of Plant-Derived Natural Biomolecule Para-Coumaric Acid in the Prevention of Oxidative Stress-Induced Diseases.

Para-coumaric acid (p-CA) is a plant derived secondary metabolite belonging to the phenolic compounds. It is widely distributed in the plant kingdom and found mainly in fruits, vegetables, and cereals. Various in vivo and in vitro studies have revealed its scavenging and antioxidative properties in the reduction of oxidative stress and inflammatory reactions. This evidence-based review focuses on the protective role of p-CA including its therapeutic potential. p-CA and its conjugates possesses various bioactivities such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-melanogenic properties. Due to its potent free radical scavenging activity, it can mitigate the ill effects of various diseases including arthritis, neurological disorders, and cardio-vascular diseases. Recent studies have revealed that p-CA can ameliorate the harmful effects associated with oxidative stress in the reproductive system, also by inhibiting enzymes linked with erectile function.

Synergistic effect of curcumin and chitosan nanoparticles on nano-hydroxyapatite-induced reproductive toxicity in rats.

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (HAPNPs), a prospective nano-biomaterial, is extensively studied, its interaction on the reproductive system following exposure is less exploited. In the present study, male rats were exposed to HAPNPs (300 mg/kg BW) to determine its possible reproductive toxicity. Also, the protective effects of chitosan (CSNPs, 280 mg/kg BW) and/or curcumin (CurNPs, 15 mg/kg BW) nanoparticles against HAPNPs-induced reproductive toxicity were studied. Animals were orally gavage daily with respective doses for 45 consecutive days. The obtained results indicated that HAPNPs caused a significant decrease in sperm count, sperm motility, testosterone hormone, steroidogenic enzymes (17-ketosteroid reductase and 17ß-hydroxysteroid dehydrogenase), and antioxidant enzymes (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase) in addition to total antioxidant capacity and reduced glutathione. LH and FSH, abnormal sperm, oxidative stress parameters (thiobarbituric acid-reactive substances (TBARS), nitric oxide (NO), and 8-hydroxy-deoxyguanosine (8-OHdG)), p53, TNFα, and interleukin-6 were significantly increased. The DNA damage was also analyzed by assaying 8-OHdG level which is considered as an indicator of genotoxicity and also suppression of the gene expression of mtTFA, induction of UCP2. Similarly, the histopathological evaluation was also changed following exposure to HAPNPs. The antioxidant activity of CSNPs and CurNPs showed mitigating effect against reproductive deterioration induced by HAPNPs throughout improvements in semen characteristics, sex hormones, inflammatory factors, and antioxidant status. The present study concluded that HAPNPs induced reproductive toxicity and it is important to use nano-antioxidants CSNPs and CurNPs as protective agents.

Dose-dependent reproductive toxicity of sodium benzoate in male rats: Inflammation, oxidative stress and apoptosis.

The synthetic food preservative sodium benzoate (SB) is widely used in both food and pharmaceutical industries. A growing body of evidence highlights the adverse effects of SB on human health; however, effect of the prolonged intake of SB on the reproductive system is not fully elucidated. The current study investigates the effect of different doses of SB (0-1000 mg/kg BW) on the reproductive system of male rats administered oral SB for 90 consecutive days. Results revealed that increasing doses of SB significantly altered the weight of reproductive organs, decreased sperm count and motility and enhanced the percentage of abnormal sperms. This was concomitant with significant decline in plasma testosterone and FSH levels, increase in plasma LH and decrease in the activities of 17ß-HSD and 17-KSR enzymes in the testes. Inflammation and oxidative stress were induced as indicated by the significant increase in TNF-α and IL-6 levels, inhibition of antioxidant enzymes activity and levels of GSH, increase in the levels of NO and TBARS and enhanced protein expression of mtTFA and UCP2 in the testes. Interestingly, p53 expression and caspase-3 activity were upregulated in the testes suggesting induction of apoptosis. Histopathological examination of the testes confirmed apoptosis and revealed degenerative alterations of the testes' architecture and perturbation of spermatogenesis. Based upon these findings, the no-observed-adverse-effect level of SB on the reproductive system was determined to be less than 1 mg/kg BW/day, highlighting the risks of long-term exposure to low as well as high doses of SB on male reproductive health.

Cardiotoxicity and lung toxicity in male rats induced by long-term exposure to iron oxide and silver nanoparticles.

Engineered nanoparticles (NPs) have been increasingly used in numerous fields over the last decade. In particular, iron oxide NPs (Fe2O3NPs) and silver NPs (AgNPs) have contributed to the current increase in NP usage. However, the possible side effects of increased NP exposure remain not fully elucidated. The present study aimed to assess the toxic effects of Fe2O3NPs and AgNPs, both individually and in combination, on the heart and lungs of male rats. To evaluate the in vivo NP toxic effects, the experimental animals were orally administered with Fe2O3NPs (5 mg/kg) and/or AgNPs (50 mg/kg). Animals were treated every day for 79 days. The results demonstrated that at the molecular level, Fe2O3NPs and AgNPs caused marked DNA base oxidation as indicated by the elevated DNA content of 8-hydroxy-2-deoxyguanosine in the heart and lungs. Fe2O3NPs and/or AgNPs decreased paraoxonase 1, antioxidant enzymes, total antioxidant capacity, and reduced glutathione in heart and lung. A dose-dependent increase in production of creatine kinase, thiobarbituric acid-reactive substances, nitric oxide end products, tumor necrosis factor-α, interleukin-6 and lipid profiles was detected. Histological changes were also evident in heart and lung tissues. The two NPs demonstrated similar toxic effects for the majority of factors when co-supplemented. In conclusion, the present study identified that Fe2O3NPs and AgNPs, alone and in combination, induced cardiotoxicity and lung toxicity. Furthermore, findings demonstrated that there was a greater toxic effect due to administration of both NPs compared to individual administration. It was hypothesized that the toxic effects may be mediated through the induction of oxidative DNA damage, lipid peroxidation, shifting redox status, disrupted gene expression, and deregulation in cytokine production.

Hepato-renal toxicity of oral sub-chronic exposure to aluminum oxide and/or zinc oxide nanoparticles in rats.

Aluminum oxide nanoparticles (Al2O3NPs) and zinc oxide nanoparticles (ZnONPs) have been involved in many industries and they are extensively abundant in many aspects of human life. Consequently, concerns have been raised about their potentially harmful effects. However the toxicities of Al2O3NPs and ZnONPs are well documented, the effect of co-exposure to both nanoparticles remains strictly obscure. Therefore, the present study was undertaken to address this issue. Four groups of male Wistar rats (10 rats each) were used; control, Al2O3NPs treated, ZnONPs treated and Co-treated groups. Rats were orally administered their respective treatment daily for 75 days. The effects of each nanoparticle alone or in combination were assessed at different levels including; hepatic and renal function, structure, and redox status, nuclear DNA fragmentation, hepatic expression of mitochondrial transcription factor A (mtTFA) gene and peroxisome proliferator-activated receptor gamma-coactivator 1α (PGC-1α), systemic inflammation, and hematologic parameters. The results confirmed the hepatorenal toxicities of each nanoparticle used at the level of all parameters with suppression of the hepatic expression of mtTFA and PGC-1α. The co-exposure to both nanoparticles results in synergistic effects. From these results, we can conclude that co-exposure to aluminum oxide nanoparticles and zinc oxide nanoparticles results in more pronounced hepatorenal toxicities and systemic inflammation.

Neuro- and nephroprotective effect of grape seed proanthocyanidin extract against carboplatin and thalidomide through modulation of inflammation, tumor suppressor protein p53, neurotransmitters, oxidative stress and histology.

The combination of thalidomide and carboplatin is one of the most potent chemotherapeutic strategies for the treatment of cancer. However, limited studies have been conducted on the neurotoxicity and nephrotoxicity of both chemotherapeutic agents. The aim of our study was to assess the toxicity of thalidomide and carboplatin combination on brain and kidney and investigate the protective effect of grape seed proanthocyanidin extract (GSPE). Thalidomide and carboplatin induced up-regulation of the expression of p53, tumor necrosis factor-α and interleukin-6 in brain and kidney. Acetylcholinesterase, dopamine and serotonin were decreased and norepinephrine was increased. Thiobarbituric acid reactive substances, nitric oxide, lipid profile, bilirubin and creatinine were elevated, while antioxidants enzymes (GST, GPX, CAT and SOD), total antioxidant capacity and the levels of glutathione were decreased. A microscopic examination showed shrinkage of capillaries, degeneration with pyknotic nuclei, loss of normal structure and neuronal degeneration. GSPE co-treatment with thalidomide and carboplatin reduced their brain and renal damage, oxidative stress, diminished cytokines, p53, neurotransmitters and biochemical parameters, and inhibited brain and renal cell apoptosis. It can be concluded that, the protective effects of GSPE against thalidomide and carboplatin induced-brain and renal damage was associated with the minimization of oxidative stress.

Protective role of Nigella sativa oil against reproductive toxicity, hormonal alterations, and oxidative damage induced by chlorpyrifos in male rats.

This study is aimed at elucidating the possible protective effects of Nigella sativa oil (NSO) in alleviating the toxicity of chlorpyrifos (CPF) on reproductive performance in male rats. Animals were orally administered with NSO (1 ml/kg/day), CPF (20 mg/kg/day), and NSO + CPF every day for 4 weeks. Results showed that CPF decreased spermatid number, sperm count, daily sperm production, and sperm motility while increased dead sperm and abnormal sperm compared with the control. Also the levels of testosterone, thyroxine levels, steroidogenic enzyme 17-ketosteroid reductase, body weight, food intake, and relative weight of reproductive organs were decreased. Thiobarbituric acid reactive substances were increased, while glutathione (GSH) and antioxidant enzymes were decreased in plasma and testes of rats treated with CPF. Histopathological examination of testes showed a decrease in the number of seminiferous tubules, form shrinkage, enlargement of the connective tissue and gametogenic changes in germ cells of rats treated with CPF. NSO alone increased testosterone, semen characteristics, GSH, and antioxidant enzymes and decreased the levels of free radicals. Furthermore, the presence of NSO with CPF alleviates its toxic effects. Our results indicated that NSO can improve semen picture and moderate CPF-induced reproductive toxicity.

Nicotine-induced reproductive toxicity, oxidative damage, histological changes and haematotoxicity in male rats: the protective effects of green tea extract.

Nicotine is an active substance present in tobacco that causes oxidative stress and tissues damages leading to several diseases. Natural antioxidants that prevent or slow the progression and severity of nicotine toxicity may have a significant health impact. We have analyzed the effects of green tea extract (GTE) on nicotine (NT)-induced reproductive toxicity, oxidative damage and haematotoxicity in adult Wistar male rats. Thirty-two rats were randomly divided into four groups: control, nicotine (NT, 1mg/kg i.p.), green tea extract (GTE, 2% w/v as the sole beverage) and (NT+GTE) group. After 2 months of treatment, blood samples were collected for measuring the haematological and oxidative stress parameters and testosterone level, while the reproductive organs were weighed and used for the semen analysis and histopathology. NT induced oxidative damage as indicated by a significant reduction in the activities of antioxidant enzymes and an elevation in TBARS levels. NT also caused reproductive toxicity as shown by a decline in testosterone levels, the weights of reproductive organs and sperm characteristics; the histological examination of testes revealed atrophy, degenerative alterations and perturbation of spermatogenesis in several seminiferous tubules, together with increased interstitial spaces and reduced number of Leydig cells. Both NT and GTE altered white blood cell count and red blood cells parameters, albeit with somewhat different effect, no protective action being seen upon NT+GTE treatment. On the contrary, GTE played a protective role against NT-induced oxidative stress as well as the reproductive effects by improving the oxidative status, semen quality and the testicular histological damage.

Ameliorative effect of docosahexaenoic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced histological changes, oxidative stress, and DNA damage in rat liver.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that leads to the development of hepatotoxicity. Docosahexaenoic acid (DHA) has been proposed to counteract oxidative stress and improve antioxidant status, and several studies suggest that supplementations with antioxidants can influence hepatotoxicity. The aim of the current study was to explore the role of DHA in modulating the toxicity of TCDD in the liver of Sprague-Dawley rats. Animals were assigned to four groups (n = 5): control (only dimethyl sulfoxide (DMSO)), 8 µg/kg body weight (b.w.) TCDD in DMSO solution; 250 mg/kg b.w. DHA and TCDD plus DHA; respectively. Rats were intraperitoneally administered their respective doses daily for 21 days. On day 21, the animals were killed, and then biochemical tests, pathological examination, and micronucleus (MN) assay were performed in the liver. Our results showed that the activities of antioxidant enzymes were significantly decreased and serious pathological findings were established in rats that received TCDD. Beside the rate of MNs in hepatocytes was increased after the treatment with dioxin. In rats treated with DHA alone, MNs were not changed and the activities of antioxidant enzymes were significantly increased. The presence of DHA with TCDD alleviated its pathological effects in hepatic tissue. DHA also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. It can be concluded that DHA has beneficial influences and could be able to antagonize TCDD toxicity in liver.