Do Nanoparticles of Calcium Disodium EDTA Minimize the Toxic Effects of Cadmium in Female Rats?

The present study aims to investigate the ability of CaNa2EDTA (ethylenediaminetetraacetic acid) macroparticles and nanoparticles to treat cadmium-induced toxicity in female rats and to compare their efficacies. Forty rats were divided into 4 equal groups: control, cadmium, cadmium + CaNa2EDTA macroparticles and Cd + CaNa2EDTA nanoparticles. Cadmium was added to the drinking water in a concentration of 30 ppm for 10 weeks. CaNa2EDTA macroparticles and nanoparticles (50 mg/kg) were intraperitoneally injected during the last 4 weeks of the exposure period. Every two weeks, blood and urine samples were collected for determination of urea, creatinine, metallothionein and cadmium concentrations. At the end of the experiment, the skeleton of rats was examined by X-ray and tissue samples from the kidney and femur bone were collected and subjected to histopathological examination. Exposure to cadmium increased the concentrations of urea and creatinine in the serum and the concentrations of metallothionein and cadmium in serum and urine of rats. A decrease in bone mineralization by X-ray examination in addition to various histopathological alterations in the kidney and femur bone of Cd-intoxicated rats were also observed. Treatment with both CaNa2EDTA macroparticles and nanoparticles ameliorated the toxic effects induced by cadmium on the kidney and bone. However, CaNa2EDTA nanoparticles showed a superior efficacy compared to the macroparticles and therefore can be used as an effective chelating antidote for treatment of cadmium toxicity.

Zinc nanoparticles ameliorate oxidative stress and apoptosis induced by silver nanoparticles in the brain of male rats.

The current study was conducted to investigate the possible ameliorative role of zinc nanoparticles (Zn NPs) against silver nanoparticles (Ag NPs)-induced oxidative and apoptotic brain damage in adult male rats. Twenty-four mature Wistar rats were randomly and equally divided into four groups: control group, Ag NPs group, Zn NPs group, and Ag NPs + Zn NPs group. Rats were exposed to Ag NPs (50 mg/kg) and/or Zn NPs (30 mg/kg) daily by oral gavage for 12 weeks. The results revealed that exposure to Ag NPs significantly increased malondialdehyde (MDA) content, decreased catalase and reduced glutathione (GSH) activities, downregulated the relative mRNA expression of antioxidant-related genes (Nrf-2 and SOD), and upregulated the relative mRNA expression of apoptosis-related genes (Bax, caspase 3 and caspase 9) in the brain tissue. Furthermore, severe neuropathological lesions with a substantial increase in the caspase 3 and glial fibrillary acidic protein (GFAP) immunoreactivity were observed in the cerebrum and cerebellum of Ag NPs-exposed rats. Conversely, co-administration of Zn NPs with Ag NPs significantly ameliorated most of these neurotoxic effects. Collectively, Zn NPs can be used as a potent prophylactic agent against Ag NPs-induced oxidative and apoptotic neural damage.

Silica Nanoparticle-Induced Reproductive Toxicity in Male Albino Rats via Testicular Apoptosis and Oxidative Stress.

Amorphous silica nanoparticles (SiNPs) are being utilized in different fields such as medicine, cosmetics, and foods. However, the causes and mechanisms underlying SiNP testicular damage remain largely unclear. In the present study, we aimed to investigate this issue. Thirty male rats were randomly divided into three groups: control group (n = 10), 500 ppm SiNP-treated group (n = 10), and 1000 ppm SiNP-treated group (n = 10). SiNPs were given orally in drinking water for 30 days. Micronucleus assay was performed on blood RBCs. The concentrations of testicular malondialdehyde (MDA) and glutathione (GSH) and catalase (CAT) activity were measured. Moreover, the histopathological alterations and the expression of apoptotic (caspase-3) and pro-inflammatory and oxidative stress markers (iNOS) in testes and epididymis were analyzed and compared between the three groups. The results showed an increased level of micronucleus frequencies in the 1000 ppm-treated group, as well as increased levels of MDA and decreased activity of CAT and GSH content in testicular tissues in the 1000 ppm-treated group, suggesting DNA damage and oxidative stress mechanisms. Also, there were significant testicular histopathological alterations in this group. Furthermore, 1000-ppm SiNPs could enhance testicular apoptosis, inflammation, and oxidative stress by increasing the expression of apoptotic, pro-inflammatory, and oxidative stress genes including caspase 3 and iNOS in the examined tissue. The lower concentration of SiNPs did not produce any significant biochemical, histopathological, or immunohistochemical alterations whereas 1000-ppm SiNPs resulted in significant testicular changes by exacerbating apoptotic, inflammatory, and oxidative stress-mediated testicular damage.

Hesperidin protects rats' liver and kidney from oxidative damage and physiological disruption induced by nickel oxide nanoparticles.

Background: Nickel oxide nanoparticles (NiO-NPs) have recently been utilized in various advanced industrial fields like lithium-ion micro batteries, nanofibers, electrochromic devices, and several biomedical applications. NiO-NPs are classified as extremely toxic substances as they can cause long-term harm to the environment and aquatic life. Moreover, frequent and prolonged exposure can affect human and animal health, causing skin allergies and major toxic consequences, such as hepatorenal toxicity. Hesperidin (HSP) has been proven to possess anti-inflammatory, antioxidant, and free radical scavenging activities. Objective: This study aimed to investigate the underlying protective mechanisms and effects of HSP against NiO-NPs-induced hepatorenal toxicities in rats. Materials and Methods: Forty male Wistar rats were randomly divided into four groups (n = 10 in each). The first group served as a Control group. For 8 weeks, the second group was administered NiO-NPs (100 mg/kg/day), and the third group was given HSP (100 mg/kg/day) via oral gavage for both groups. The fourth group received NiO-NPs and HSP concurrently in the same oral daily doses and duration as the second and third groups. Results: NiO-NPs administration revealed a significant increase in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (ALT, AST) in NiO-NPs group compared to Control group (p < 0.05). In addition, NiO-NPs administration resulted in a substantial increase in malondialdehyde levels with a significant drop in catalase activity and GSH content in Group II. Also, a significant decreased expression of Nrf-2 and Bcl-2 mRNA levels and upregulation of TNF-α, NF-kß and BAX in the liver and kidney of NiO-NPs group were also detected. Histologically, the liver and kidney of rats of NiO-NPs group showed significant histopathological disturbances, with a substantial increase in the proliferating cell nuclear antigen (PCNA) positive hepatocytes and renal tubular cells in the NiO-NPs group compared to Control and HSP groups (p < 0.05). In contrast, concomitant administration of HSP with NiO-NPs in group IV showed a significant biochemical, histopathological, and immunohistochemical improvement compared to NiO-NPs group. Conclusion: Co-administration of HSP with NiO-NPs significantly ameliorated most of the NiO-NPs-induced hepatorenal toxicities in male rats.

Antioxidant and antiapoptotic effects of quercetin against ochratoxin A-induced nephrotoxicity in broiler chickens.

The mycotoxin ochratoxin A (OTA) is produced by the fungi Aspergillus and Penicillium. The flavonoid quercetin (QUE) is distinguished by its antioxidant, anti-inflammatory, and antiapoptotic properties. This study was designed to determine whether QUE can protect broiler chickens against OTA-induced nephrotoxicity. Forty broiler chicks were randomly divided into four equal groups: control, OTA, QUE, and OTA + QUE. For 6 weeks, OTA (0.5 mg/kg) and/or QUE (0.5 g/kg) were added to the diet of chickens. The results demonstrated that OTA exposure increased serum levels of creatinine, uric acid, and blood urea nitrogen. OTA exposure also increased renal malondialdehyde content but decreased renal antioxidants. OTA-exposed chickens exhibited multiple pathological kidney lesions. Moreover, OTA exposure induced apoptosis in renal tissue, which was manifested by the up-regulation of proapoptotic genes and down-regulation of antiapoptotic genes via the suppression of the PI3K/AKT pathway. In addition, coadministration of QUE and OTA mitigated most of these nephrotoxic effects.

Protective Effects of Bacillus Subtilis Fermentation Extract Against Ochratoxin A-induced Nephrotoxicity and Immunotoxicity in Broiler Chickens.

Introduction: Ochratoxin A (OTA) is a mycotoxin notably produced by Aspergillus and Penicillium spp. Bacillus subtilis fermentation extract (BSFE) contains specific enzymes which hydrolyse OTA. This study evaluated the efficiency of BSFE in ameliorating the immunotoxic and nephrotoxic effects of OTA in broiler chickens. Material and Methods: Day-old broiler chicks were divided equally into four groups of ten: control, OTA (0.5 mg/kg feed), BSFE product (1 mL/L water) and OTA + BSFE at the same concentrations. The chicks were vaccinated against avian influenza, Newcastle disease, and infectious bronchitis, and lymphoproliferation was induced in all birds by phytohaemagglutinin-P (PHA-P). Serum samples were taken before sacrifice and organ tissue samples were taken after, in which renal function biomarkers were assayed and the presence of OTA residue was evaluated by high-performance thin-layer chromatography. Protein markers of apoptosis were determined by qPCR, and tissue lesions were examined histopathologically. Results: Exposure to OTA significantly decreased the antibody response to the vaccines and the lymphoproliferative response to PHA-P, and significantly elevated the renal function indicators: serum urea, uric acid and creatinine. It also induced oxidative stress (reduced catalase activity and glutathione concentration), lipid peroxidation (increased malondialdehyde content), apoptosis (increased Bax and Caspase-3 and decreased Bcl-2 gene levels) and pathological lesions in kidney, bursa of Fabricius, spleen and thymus tissue. Residues of OTA were detected in the serum and tissue. BSFE mitigated most of these toxic effects. Conclusion: BSFE counters OTA-induced immunotoxicity and nephrotoxicity because of its content of carboxypeptidase and protease enzymes.

Alterations in reproductive parameters and steroid biosynthesis induced by nickel oxide nanoparticles in male rats: The ameliorative effect of hesperidin.

With recent progress in the manufacture and applications of nickel oxide nanoparticles (NiO NPs), concerns about their adverse effects are increasing. Hesperidin (HSP) is a citrus flavonoid that has a potent anti-inflammatory, antioxidant and free radical scavenging activities. This study aims to investigate the protective effect of HSP against testicular and spermatological damages induced by NiO NPs in male rats. Forty rats were randomly and equally divided into four groups: control, NiO NPs, HSP and NiO NPs + HSP. NiO NPs (100 mg/kg) and/or HSP (100 mg/kg) were given daily by gavage for 60 days. Exposure to NiO NPs induced marked reproductive toxicity in male rats that was manifested by increased sperm abnormalities and deterioration of sperm motility, count and viability. NiO NPs also increased lipid peroxidation and negatively affected the cellular antioxidant defense system in the testis of rats. The level of serum testosterone hormone was increased in NiO NPs-exposed rats. qPCR showed a marked downregulation in expression of steroidogenesis-related genes (CYP11A1, HSD3B and STAR) and a significant upregulation in expression of apoptosis-related gene (caspase-9) in testicular tissue of rats. Various pathological lesions and an increase in the number of PCNA-positive immune-reactive cells were also noticed in the testis of NiO NPs-exposed rats. Co-administration of HSP significantly ameliorated most of the NiO NPs-induced testicular damages and improved male fertility in rats.

Evaluation of the Ameliorative Effect of Zinc Nanoparticles against Silver Nanoparticle-Induced Toxicity in Liver and Kidney of Rats.

Silver nanoparticles (Ag-NPs) have various pharmaceutical and biomedical applications owing to their unique physicochemical properties. Zinc (Zn) is an essential trace element, a strong antioxidant, and has a primary role in gene expression, enzymatic reactions, and protein synthesis. The present study aims to explore the toxic effects of Ag-NPs (50 nm) on the liver and kidney of rats and also to evaluate the potential protective effect of Zn-NPs (100 nm) against these adverse effects. Forty adult Sprague-Dawley rats were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, and Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered daily by gavage for 90 days. The results showed that exposure to Ag-NPs increased serum ALT, AST, urea, and creatinine. Ag-NPs also induced oxidative stress and lipid peroxidation and increased inflammatory cytokines in hepatic and renal tissues. Moreover, histopathological and immunohistochemical examinations revealed various histological alterations and positive caspase-3 expressions in the liver and kidney following exposure to Ag-NPs. On the other hand, most of these toxic effects were ameliorated by co-administration of Zn-NPs. It was concluded that Ag-NPs have hepatotoxic and nephrotoxic effects in rats via different mechanisms including oxidative stress, inflammation, and apoptosis and that Zn-NPs can be used to alleviate these harmful effects by their antioxidative, anti-inflammatory, and antiapoptotic properties.

Quercetin ameliorates ochratoxin A-Induced immunotoxicity in broiler chickens by modulation of PI3K/AKT pathway.

Ochratoxin A (OTA) is a fungal secondary metabolite produced by certain species of Aspergillus and Penicillium, and exerts immunosuppressive effect on humans and animals. Quercetin (QUE) is one of the flavonoids produced as a plant-secondary metabolite. The present study was designed to evaluate the efficacy of QUE against the immunotoxic hazard of OTA in broiler chickens. Forty one-day-old broiler chicks were randomly and equally allocated into four groups; control, OTA (0.5 mg/kg feed), QUE (0.5 g/kg feed) and OTA + QUE (0.5 mg/kg OTA + 0.5 g/kg QUE). The results revealed that dietary OTA induced a significant decrease in the antibody response to Newcastle Disease (ND), Infectious Bronchitis (IB) and Avian Influenza (AI) vaccination and in the lymphoproliferative response to Phytohemagglutinin-P (PHA-P). Ochratoxin A also induced oxidative stress and lipid peroxidation in the bursa of Fabricius, spleen and thymus tissues of chickens as demonstrated by decreased CAT and GSH levels and increased TBARS content. In addition, administration of OTA resulted in apoptosis, which was evident by the increased expression level of PTEN, Bax and Caspase-3 genes and decreased expression level of PI3K, AKT and Bcl-2 genes. Furthermore, exposure to OTA resulted in various pathological lesions in the bursa of Fabricius, spleen and thymus of chickens. On the other hand, administration of QUE ameliorated most of the immunotoxic effects of OTAby its immunomodulatory, antioxidant and anti-apoptotic activities. Taken together, the results suggested that QUE potentially alleviated the OTA-induced immunotoxicity in broiler chickens, probably through amelioration of oxidative stress and activation of the PI3K/AKT signaling pathway.

Neuroprotective effect of hesperidin against emamectin benzoate-induced neurobehavioral toxicity in rats.

Emamectin Benzoate (EMB) is an avermectin insecticide widely used in agriculture and veterinary medicine. Hesperidin (HSP) is a flavanone glycoside predominantly found in citrus fruits and has various beneficial health effects. The current research was conducted to study the neurobehavioral toxic effects of EMB in rats and also to evaluate the protective effect of HSP against these toxic effects. Sixty Sprague-Dawley rats were randomly divided into 4 equal groups: control group, EMB group, HSP group, and EMB + HSP group. EMB (8.8. mg/kg) and/or HSP (100 mg/kg) were administered daily by gavage for 8 weeks. The behavioral assessment demonstrated the adverse effects of EMB on the behavioral, motor, and cognitive brain functions. Exposure to EMB also decreased the activity of antioxidants (catalase and reduced glutathione) and increased the malondialdehyde level in nervous tissue. Moreover, EMB increased the level of inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) and decreased brain-derived neurotrophic factor (BDNF) levels in rats' brains. On the other hand, concurrent administration of HSP ameliorated the toxic effects of EMB as indicated by improvements in neural functions and reduction of oxidative stress and inflammation. The study concluded that exposure to EMB induces toxic effects in the brain of rats and that HSP has a protective effect against these toxic effects.

Zinc Nanoparticles Ameliorate the Reproductive Toxicity Induced by Silver Nanoparticles in Male Rats.

INTRODUCTION: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects. METHODS: Forty adult male rats were used in this study; they were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered orally for 90 days. RESULTS: The results revealed that exposure to Ag-NPs adversely affected sperm motility, morphology, viability, and concentration. Ag-NPs also induced oxidative stress and lipid peroxidation in testicular tissue. The exposure to Ag-NPs decreased serum FSH, LH, and testosterone hormones. Additionally, comet assay revealed DNA degeneration in the testicular tissue of rats exposed to Ag-NPs. Histopathological examination showed various histological alterations in the testes of rats intoxicated with Ag-NPs. Furthermore, co-administration of Zn-NPs ameliorated most of the toxic effects of Ag-NPs via their antioxidative capacity.

Postmortem expression of apoptosis-related genes in the liver of mice and their use for estimation of the time of death.

PURPOSE: A major challenge in forensic medicine is to estimate the postmortem interval (PMI). Several approaches had been tried to determine the time of death, including physical and chemical changes. This study aims to explore the postmortem changes in the expression of apoptosis-related genes in the liver of mice and to use these changes for estimation of the PMI. METHODS: Hepatic tissue was collected from sacrificed mice immediately after death (the control group) and at 3, 6, 9, 12, 18, and 24 hours after death. Four apoptosisrelated genes were selected as target genes, which are Caspase 3 (Casp3), B cell leukemia/ lymphoma 2 (Bcl2), BCL2-associated X protein (Bax), and Transformation related protein 53 (Trp53), and their relative expression was measured using quantitative PCR. miR-122 was used as a reference gene for normalization of the Ct (threshold cycle) values of the target genes. RESULTS: The results revealed that the postmortem expression of Casp3 increased in a time-dependent manner; the expression of Bax increased from 3 to 18 hours followed by a decrease at 24 hours after death; the expression of Bcl2 decreased in a time-dependent manner after death; the expression of Trp53 increased from 3 to 6 hours and then started to decrease from 9 to 24 hours after death. CONCLUSION: Based on the observed changes in the expression level of these genes, mathematical models were established to estimate the PMI. Further research is needed to investigate these markers and mathematical models in human tissues.

Carvacrol ameliorates behavioral disturbances and DNA damage in the brain of rats exposed to propiconazole.

Propiconazole (PCZ) is an ergosterol biosynthesis inhibiting fungicide. Carvacrol (CAR) is a monoterpenoid phenol that has various beneficial health effects. The current research was designed to study the impact of PCZ on the behavior of rats and its ability to induce DNA damage in neurons as well as to clarify the ameliorative effect of CAR against these toxic impacts. Sixty Sprague-Dawley rats were randomly and equally divided into 4 experimental groups and treated daily by oral gavage for 2 months as follows: Group 1 (control); group 2 treated with PCZ (75 mg/kg); group 3 treated with CAR (50 mg/kg) and group 4 treated with both PCZ and CAR. Behavioral tests demonstrated that exposure to PCZ had a deleterious effect on psychological, motor and cognitive neural functions. Additionally, antioxidant enzyme activities, SOD and GSH-Px, were declined in brain tissue following exposure to PCZ. Moreover, comet assay revealed a high percent of DNA damage in the brain of rats exposed to PCZ. On the other hand, CAR administration ameliorated the harmful effects induced by PCZ through a protective mechanism that involved the improvement of neural functions and attenuation of oxidative stress and DNA damage.

Ameliorative effect of carvacrol against propiconazole-induced neurobehavioral toxicity in rats.

Propiconazole (PCZ) is a triazole fungicide extensively used in agriculture. Carvacrol (CAR) is a naturally occurring phenolic monoterpene which has various biological and pharmacological effects. The present study was designed to investigate the neurobehavioral toxic effects of PCZ in albino rats and to evaluate the ameliorative role of CAR against such toxic effects. Sixty adult male rats were used in this investigation; they were randomly and equally divided into 4 groups: control group, PCZ group, CAR group and PCZ + CAR group. PCZ (75 mg/kg) and/or CAR (50 mg/kg) were administered daily by oral gavage for 8 weeks. Behavioral investigation clearly demonstrated the negative impact of PCZ on psychological, motor and cognitive brain functions. Exposure to PCZ also adversely affected the measured oxidative stress and lipid peroxidation parameters in brain tissue. A significant decrease in activity of acetylcholinesterase enzyme in neural tissue was also observed in PCZ-exposed rats. Histopathological examination of the cerebrum, cerebellum, and hippocampus showed various histopathological lesions after exposure to PCZ which were confirmed by immunohistochemical examination. On the other hand, co-administration of CAR ameliorated most of the undesirable effects of PCZ.

Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.

Although the widespread use of titanium dioxide nanoparticles (TiO2 NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO2 NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\Kg BW), group III received TiO2 NPs plus tiron (470mg\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-ß1 (TGFß1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO2 NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFß1 and MMP9. Oral administration of tiron to TiO2 NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO2 NPs through its radical scavenging and metal chelating potency.

Reproductive toxicity provoked by titanium dioxide nanoparticles and the ameliorative role of Tiron in adult male rats.

Titanium dioxide nanoparticles (TDN) are widely used in paints, plastics, ceramics, cosmetics, printing ink, rubber and paper. Tiron is a water soluble metal chelator and antioxidant. This study was designed to investigate the reproductive toxicity of TDN in male albino rats and the ameliorative role of Tiron to minimize such toxic effects. Eighty adult male albino rats were assigned into 4 equal groups, group 1: control; group 2: received TDN at 100 mg/kg/day orally for 8 weeks; group 3: received Tiron at 470 mg/kg/day intraperitoneally for 2 weeks (the last 2 weeks of the experimental period); group 4: received both TDN and Tiron by the same previously mentioned dose, route and duration. The results revealed that TDN provoked reproductive toxicity which was proved by the deteriorated spermogram picture, high incidence of micronucleated RBCs, elevated oxidative stress parameters and up regulation of Testin gene. Whereas, Tiron co-treatment ameliorated most of these toxic alterations. Our findings highlighted the protective role of tiron against TDN intoxication.