TY - JOUR AU1 - Rezk, Mohamed, M AU2 - Dhmees, Abdelghaffar, S AU3 - Abd El-Magied,, Mahmoud O AU4 - Manaa, El-Sayed, A AU5 - El-Gendy, Hassan, S AB - Abstract Effect of cobalt manganese ferrite nanoparticles (M-NPs) (Co0.5Mn0.5Fe2O4) on vanadium hazards was assessment in the present study. Four groups of adult male albino rats [control group and three variably treated groups with ammonium metavanadate accompanied with or without cobalt M-NPs] were studied. The oral administration of ammonium metavanadate (Am.V) (20 mg/kg b.wt.) demonstrated the facility of vanadium to distribute and accumulate in the distinctive body organs and ordered as kidney > liver > lung > brain > spleen. Also, Am.V administration induce a significant disturbance in many physiological parameters (RBS, cholesterol, triglyceride, aspartate transaminase, alanine transaminase, Alb., bilirubin, Alk.Ph., urea, creat., Hb%, red blood cell count and packed cell volume) which might be expected to the liberation of free radicals according to the vanadium intoxication or its ability to disturb many body metabolisms. On the other hand, the intraperitoneal administration of 5% M-NPs in parallel with Am.V orally administration showed the ability of M-NPs to reduce Am.V dangerous impacts, which might be resulted from the essentiality of M-NPs metals to the body metabolism and to its free radicals scavenging properties. So, M-NPs could reduce Am.V hazardous effects. vanadate, nanoparticles, liver, kidney, hematology, rat Introduction Vanadium is one of the transition metals, with various and wide industrial uses and catalysts applications. These various application increases vanadium level in the environment, which transferees to human and living organisms through food and water [1–7]. Vanadium can enter the body via the lungs or, more commonly, the stomach. Vanadium transported in the blood via transferrin or albumin. From the bloodstream, vanadium distributed to the body tissues leads to some gastrointestinal problems (diarrhea, vomiting, general dehydration with weight reduction, intestinal inflammation and a characteristic green tongue), pulmonary inflammation, impaired lung function and respiratory irritation. Excess of vanadium exposure causes immunotoxicity, behavioral toxicity, carcinogenic chromosomal aberrations, paralysis, convulsion and eventually death [8–12]. There is an increased interest in developed new technologies to remove vanadium from the environment to reduce its hazardous effect on human and living organisms. One of the most interesting technologies to achieve this goal is the use of nano- and micro-particles that have the capability to remove vanadium and its hazards compounds from the environments. Nanoparticles (NPs) have gained considerable interest because of their unique physical and chemical properties, as well as wide-ranging potential applications [13–19]. NPs have different applications in the environmental, medical, tissue engineering, analytical and oil industries [20–33]. Ferrites nanoparticles (MFe2O4) have attracted considerable interest due to their unique chemical and physical properties. Cobalt ferrites are hard ferrite materials because of their excellent chemical stability and mechanical hardness. Cobalt ferrites NPs have different applications in adsorption, catalysts, drug delivery, biomedical diagnostics, etc [34–43]. The unit cell of ferrites is composed of 32 oxygen atoms in a cubic closed-packed arrangement distributed in tetrahedral and octahedral sites. The physical and chemical properties of these particles are improved by doping ferrite NPs with various metals, such as copper, manganese and zinc [34–36]. Accordingly, efforts have already been made to substitute Co or Fe by different metal ions [34–36]. Manganese ferrite has good mechanical and chemical stability; the cobalt cations involved in cobalt ferrite can migrate from octahedral to tetrahedral places. However, the migration of manganese cations included in the manganese ferrite is from tetrahedral to octahedral places [34–37]. The present study aims to improve the knowledge of ammonium metavanadate (Am.V) toxic effects, which were to date rarely reported. Another goal of this manuscript is to study the influence of Co0.5Mn0.5Fe2O4 nanoparticles (M-NPs) on the reduction of hazardous effects of toxic Am.V in adult rats. Materials and Methods Materials and preparation of Co0.5Mn0.5Fe2O4 NPs Am.V NH4VO3 (99%) was obtained from Sigma-Aldrich (Germany). The Am.V/rat dose was 20 mg/Kg which is equivalent to 1/5 of LD50 (Supplementary information, SI). For the preparation of Co0.5Mn0.5Fe2O4 NPs ferric nitrate Fe(NO3)3.9H2O (99%) purchased from Loba (Mumbai, India), cobalt nitrate Co(NO3)2·6H2O (99%, Merck, Darmstadt, Germany), manganese nitrate Mn(NO3)2·4H2O (97%) and citric acid C6H8O7 (99.5%, Sigma-Aldrich) were used. The cobalt manganese ferrite was synthesized by the citrate precursor method. Stoichiometric amounts of metal nitrate were weighed separately and dissolved in 50 ml of deionized water to make a clear solution; then mixed and stirred for 1 h at ambient temperature to get a homogenous solution. Citric acid was dissolved in deionized water and added to the former solution. Cobalt manganese ferrite NPs (Co0.5Mn0.5Fe2O4) were prepared from nitrate salts of metals (the metal nitrate to citric acid molar ratio was 1:5). The solution was stirred at 90°C until the viscous gel was formed. The obtained viscous gel was transferred to the furnace at 170°C. Finely powdered materials were annealed at 500°C for further crystallization. The obtained cobalt manganese ferrite NPs were characterized by the Malvern Nano ZS90 Zetasizer Nanoseries system (Malvern, Worcestershire, UK), Nicolet iS10 Fourier Transform Infrared spectroscopy. The prepared M-NPs (3–20 nm particle size) were before use dispersed in phosphate buffer saline. Animals grouping and treatment Rattus rattus (110 ± 20 g) were purchased from Research National Center, Giza, Egypt (Supplementary information file, SI). Rats were randomly grouped into four groups as follows. Control group Animals of this group were daily orally administered first with distilled water (0.5 ml/100 g rat) using stomach tube then were after 1 h intraperitoneal (IP) injected with 0.5 ml of phosphate buffer saline for 15 days. V (Vanadate) group Animals of this group were daily orally administered with 20 mg/kg of Am.V for 15 days. M-NPs (NPs) group The animals in this group were IP injected with phosphate-buffer saline suspension contains 5% of M-NPs for 15 days. V+ M-NPs group Animals of this group were daily orally administered first with Am.V (20 mg/kg b.wt.) using stomach tube and were after 1 h IP injected with 5% of phosphate-buffer saline suspension of M-NPs for 15 days. The 96 rats of different groups were decapitated after the 3rd, 7th, 10th and 15th day (six rats for each decapitation) during the treatment. Blood samples were collected and divided into two small sterilized tube one of them containing ethylene-diamine-tetra-acetic acid (EDTA) as an anticoagulant for hematological parameters, and the other tube without EDTA standing in a water bath at 37°C and centrifuged for 15 min at 3000 rpm to obtain serum then stored in labeled Eppendorf for further physiological analyses. Determination of vanadium Each organ (liver, kidney, spleen, heart, testes and lung) was placed in a separate Teflon beaker and was applied to acid digestion in the presence of nitric acid, perchloric acid and hydrogen peroxide to 130°C till complete dryness. The ashes in the beaker were dissolved by diluted 1:1 hydrochloric acid (SI) [44, 45]. Vanadium content in the resulted solution was estimated by atomic absorption analysis with graphite furnace atomization (AAS; Thermal-Jarrel Ash Model 12 Spectrophotometer). Biochemical assays Determination of hemoglobin (Hb), hematocrit (PCV) and red blood cell count (RBCs) Using the whole blood samples (EDTA tubes), Hb content was estimated using the cyanmethemoglobin method described by Zijlstra and Kampene [46] and modified by Marie [47], (bio Merieux Kit) where Hb was converted into cyanmethemoglobin, under the influence of potassium ferricyanide and potassium cyanide and was measured at 540 nm in spectronic 601 spectrophotometer. RBCs count was carried out using the improved Neubauer hemocytometer. Packed cell volume (PCV) hematocrit is determined by taken a known volume of fully oxygenated, uncoagulated blood was centrifuged at 3000 rpm for 10 min in a heparinized micro-hematocrit capillary tube until the cells were packed down to constant volume [48]. The percentage of the relative volume of the erythrocytes to that of the whole blood was determined using the hematocrit reader. Serum analysis Blood samples were collected after decapitation and centrifuged after standing for 15 min in a water bath at 35°C and stored at −20°C. Then, the samples were analyzed using an automated analyzer (Boehringer Mannheim/Hitachi 902 system, Roche Diagnostic, Japan). The analysis includes glucose [49], kidney functions as creatinine [50], urea and uric acid [51], liver functions as alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) [52], bilirubin (Bil) [53], lipid profile cholesterol (chol.), triglyceride (trig.) [54]. Statistical analysis The statistical analysis of data was carried out by using a one-way analysis of variance (ANOVA). The Statistical Package for the Social Science version 20. Results Nano-materials characterization Various types of ferrite have been prepared using a variety of methods, such as co-precipitation, hydrothermal synthesis, chemical, sol-gel and combustion synthesis [34–40]. Production of various ferrites using a sol-gel technique is a particularly simple, safe and rapid process yielding homogeneous, high-purity NPs. So, in this study cobalt manganese ferrite NPs, Mn0.5Co0.5Fe2O4 was synthesized by the citrate precursor method (Fig. 1). Figure 1 Open in new tabDownload slide Synthesis of Co0.5Mn0.5Fe2O4 through citrate precursor method. Figure 1 Open in new tabDownload slide Synthesis of Co0.5Mn0.5Fe2O4 through citrate precursor method. The suggested mechanism of the formation of the M-NPs at MnO and CoO interfaces or at Fe2O3 interface is given by equations (1) and (2), respectively [34–37]: $$\begin{equation} 2{\mathrm{Fe}}^{2+}+1.5\mathrm{MnO}+1.5\mathrm{CoO}+0.5{\mathrm{O}}_2\to 2{\mathrm{Mn}}_{0.5}{\mathrm{Co}}_{0.5}{\mathrm{Fe}}_2{\mathrm{O}}_4+{\mathrm{Mn}}^{2+}+{\mathrm{Co}}^{2+} \end{equation}$$(1) $$\begin{equation} 3{\mathrm{Fe}}_2{\mathrm{O}}_3+{\mathrm{Mn}}^{2+}+{\mathrm{Co}}^{2+}\to 2{\mathrm{Mn}}_{0.5}{\mathrm{Co}}_{0.5}{\mathrm{Fe}}_2{\mathrm{O}}_4+2{\mathrm{Fe}}^{2+}+0.5{\mathrm{O}}_2. \end{equation}$$(2) The co-existence of Co, Mn and Fe elements in the M- NPs were analyzed by X-ray Powder Diffraction (XRD) and Energy Dispersive X-Ray (EDX) analysis, which confirmed the presence of these elements the M-NPs (Figs 2 and 3). Figure 2 shows the XRD pattern of the M-NPs (JCPDS card No. 04–008-8148). The peaks corresponding to Mn0.5Co0.5Fe2O4 at 2θ values of 30.29, 35.81, 43.86, 57.10 and 62.92, were observed [34–37]. Figure 2 Open in new tabDownload slide Characterization of M-NPs by XRD. Figure 2 Open in new tabDownload slide Characterization of M-NPs by XRD. Figure 3 Open in new tabDownload slide EDX of Co0.5Mn0.5Fe2O4. Figure 3 Open in new tabDownload slide EDX of Co0.5Mn0.5Fe2O4. The EDX analysis (Fig. 3) gives the qualitative composition of M-NPs and also confirms the co-existence of Co, Mn and Fe elements in the M-NPs with the relative abundance of Co and Mn much closer to each other. This indicates the homogeneous distribution of Co and Mn in the M-NPs studied. Figure 3 clearly shows that no extra impurities are present in the M-NPs, and also it has been observed that the ratio of the elements is close to the empirical formula. The surface M-NPs were verified using Fourier-transform infrared spectroscopy (FTIR) (Fig. 4), the peaks located at 1634 and 3417 cm−1 are assigned to the stretching vibration peak of adsorbed water, which is always detected in the prepared ferrite NPs. The band near 466 cm−1 is assigned to the metal-oxygen bands at the tetrahedral site, where the band at 593 cm−1 is assigned to the bending vibrations of the (M–O) bonds in the octahedral site [35]. Figure 4 Open in new tabDownload slide FTIR spectrum of Co0.5Mn0.5Fe2O4. Figure 4 Open in new tabDownload slide FTIR spectrum of Co0.5Mn0.5Fe2O4. The Dynamic Light Scattering (DLS) analysis of M-NPs showed the size of NPs in the range of 3–20 nm in diameter. In order to evaluate the stability of NPs and to determine pHpzc, the zeta potential was also measuring. The obtained pHpzc value was 5.8. Biochemical assays A significant increase in vanadium ions content was observed in different body organs at the end of the experiment in both V and V + M-NPs groups as compared to control value which was under the detection limit as shown in Fig. 5. As comparing V + M-NPs to V group, vanadium ions content showed a significant decrease. Figure 5 Open in new tabDownload slide Vanadium ions accumulation (μg/g) in different organs of adult male albino rats intoxicated with Am.V (20 mg/kg b.wt.) alone (V group) or followed by IP administration with 5% of M-NPs (V + M-NPs group). n = 6, significant change at P < 0.05, where ‘a’ significant to control the group and `b' significant to V group. Figure 5 Open in new tabDownload slide Vanadium ions accumulation (μg/g) in different organs of adult male albino rats intoxicated with Am.V (20 mg/kg b.wt.) alone (V group) or followed by IP administration with 5% of M-NPs (V + M-NPs group). n = 6, significant change at P < 0.05, where ‘a’ significant to control the group and `b' significant to V group. The daily oral administration of vanadium induced a significant decrease in Hb content on the 15th day of administration, while the administration of M-NPs induced a significant increase in its content on both the 11th and 15th days of the experiment. A non-significant change in Hb content was observed on the groups of V + M-NPs administration. PV showed a significant decrease in its value as a result of vanadium administration, while in M-NPs administration, it showed a significant increase at the end of the experiment as compared to control value. The only significant change in RBCs count for the three groups was observed on the 11th and 15th days of the V group as a decreasing level (Table 1). In comparison to the V group, the administration of V and M-NPs induced a significant increase in the last two decapitations for Hb content and HCT value, and on the last week for RBCs count. Table 1 Effect of 5% M-NPs IP on hematological parameters in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals Hb . 3 Day . 7 Day . 11 Day . 15 Day . Control 9.37 9.51 9.43 9.16 V 9.11 8.95 8.68 7.95a % −2.77 −5.89 −7.95 −13.21 M-NPs 9.86 10.11 10.58 11.5 % 5.23 6.31 12.20 25.55 V + M-NPs 9.23 9.24 9.68b 9.55b % −1.49 −2.48 2.65 4.26 RBCs 3 Day 7 Day 11 Day 15 Day Control 8.32 8.44 8.42 8.65 V 7.95 7.65 7.35a 7.21a % −4.45 −9.36 −12.71 −16.65 M-NPs 8.55 8.24 8.63 8.24 % 2.76 −2.37 2.49 −2.74 V + M-NPs 8.21 7.68 7.54 8.10b % −1.32 −9.00 −10.45 −6.36 HCT 3 Day 7 Day 11 Day 15 Day Control 29.05 29.48 29.23 28.39 V 28.24 27.74 26.90 25.88a % −2.77 −5.89 −7.95 −13.21 M-NPs 30.56 31.34 32.79a 35.65a % 5.23 6.31 12.20 25.55 V + M-NPs 28.61 28.64 30.01b 29.60b % −1.49 −2.84 2.65 4.26 Hb . 3 Day . 7 Day . 11 Day . 15 Day . Control 9.37 9.51 9.43 9.16 V 9.11 8.95 8.68 7.95a % −2.77 −5.89 −7.95 −13.21 M-NPs 9.86 10.11 10.58 11.5 % 5.23 6.31 12.20 25.55 V + M-NPs 9.23 9.24 9.68b 9.55b % −1.49 −2.48 2.65 4.26 RBCs 3 Day 7 Day 11 Day 15 Day Control 8.32 8.44 8.42 8.65 V 7.95 7.65 7.35a 7.21a % −4.45 −9.36 −12.71 −16.65 M-NPs 8.55 8.24 8.63 8.24 % 2.76 −2.37 2.49 −2.74 V + M-NPs 8.21 7.68 7.54 8.10b % −1.32 −9.00 −10.45 −6.36 HCT 3 Day 7 Day 11 Day 15 Day Control 29.05 29.48 29.23 28.39 V 28.24 27.74 26.90 25.88a % −2.77 −5.89 −7.95 −13.21 M-NPs 30.56 31.34 32.79a 35.65a % 5.23 6.31 12.20 25.55 V + M-NPs 28.61 28.64 30.01b 29.60b % −1.49 −2.84 2.65 4.26 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05. Open in new tab Table 1 Effect of 5% M-NPs IP on hematological parameters in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals Hb . 3 Day . 7 Day . 11 Day . 15 Day . Control 9.37 9.51 9.43 9.16 V 9.11 8.95 8.68 7.95a % −2.77 −5.89 −7.95 −13.21 M-NPs 9.86 10.11 10.58 11.5 % 5.23 6.31 12.20 25.55 V + M-NPs 9.23 9.24 9.68b 9.55b % −1.49 −2.48 2.65 4.26 RBCs 3 Day 7 Day 11 Day 15 Day Control 8.32 8.44 8.42 8.65 V 7.95 7.65 7.35a 7.21a % −4.45 −9.36 −12.71 −16.65 M-NPs 8.55 8.24 8.63 8.24 % 2.76 −2.37 2.49 −2.74 V + M-NPs 8.21 7.68 7.54 8.10b % −1.32 −9.00 −10.45 −6.36 HCT 3 Day 7 Day 11 Day 15 Day Control 29.05 29.48 29.23 28.39 V 28.24 27.74 26.90 25.88a % −2.77 −5.89 −7.95 −13.21 M-NPs 30.56 31.34 32.79a 35.65a % 5.23 6.31 12.20 25.55 V + M-NPs 28.61 28.64 30.01b 29.60b % −1.49 −2.84 2.65 4.26 Hb . 3 Day . 7 Day . 11 Day . 15 Day . Control 9.37 9.51 9.43 9.16 V 9.11 8.95 8.68 7.95a % −2.77 −5.89 −7.95 −13.21 M-NPs 9.86 10.11 10.58 11.5 % 5.23 6.31 12.20 25.55 V + M-NPs 9.23 9.24 9.68b 9.55b % −1.49 −2.48 2.65 4.26 RBCs 3 Day 7 Day 11 Day 15 Day Control 8.32 8.44 8.42 8.65 V 7.95 7.65 7.35a 7.21a % −4.45 −9.36 −12.71 −16.65 M-NPs 8.55 8.24 8.63 8.24 % 2.76 −2.37 2.49 −2.74 V + M-NPs 8.21 7.68 7.54 8.10b % −1.32 −9.00 −10.45 −6.36 HCT 3 Day 7 Day 11 Day 15 Day Control 29.05 29.48 29.23 28.39 V 28.24 27.74 26.90 25.88a % −2.77 −5.89 −7.95 −13.21 M-NPs 30.56 31.34 32.79a 35.65a % 5.23 6.31 12.20 25.55 V + M-NPs 28.61 28.64 30.01b 29.60b % −1.49 −2.84 2.65 4.26 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05. Open in new tab Glucose level showed a significant increase on the last day of the experiment as a result of vanadium gavage with or without M-NPs IP injection as compared to control, while on the nano-group, a non-significant change was observed all over the experimental period. The daily orally administration of vanadium induced a significant increase in both chol. and trig. on the 7th, 11th and 15th days of administration, elsewhere, although both chol. and trig. showed non-significant change after M-NPs IP injection, they showed a significant increase when the injection was paralleled with vanadium administration as compared to control value (Table 2). The daily orally administration of vanadium induced a significant increase in AST and ALT enzyme levels on the 11th and 15th day for AST and only on the 15th day for ALT. In spite of being significantly increased on the 15th day, AST, as well as ALT, showed a non-significant change throughout the experimental period on both groups M-NPs and V + M-NPs groups as compared to control. ALK. Ph enzyme level showed a sudden significant increase starting on the third day of vanadium administration, and progress reaching its maximum value on the 15th day as compared to control. While on the V + M-NPs group a significant increase in ALK. The level was noticed on the 11th and 15th days of treatment (Bil). Table 2 Effect of 5% M-NPs IP on glucose, chol. and trig. in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals Glucose . 3 Day . 7 Day . 11 Day . 15 Day . Control % 97.5 98.21 96.21 95.36 V 100.32 99.32 105.32 110.12a % 2.89 1.13 9.47 15.48 M-NPs 97.7 98.41 96.41 95.56 % 0.21 0.20 0.21 0.21 V + M-NPs 97.11 96.11 102.11 106.91a % −0.40 −2.14 6.13 12.11 Chol. 3 Day 7 Day 11 Day 15 Day Control 132.25 133.22 129.21 128.25 V 144.55 151.35a 159.33a 165.32a % 9.30 13.61 23.31 28.90 M-NPs 130.45 131.26 127.59 121.36 % −1.36 −1.47 −1.25 −5.37 V + M-NPs 137.89 139.33 145.68a 155.24a % 4.26 4.59 12.75 21.04 Trig. 3 Day 7 Day 11 Day 15 Day Control 107.21 104.65 102.35 105.32 V 110.25 124.98a 135.68a 145.32a % 2.84 19.43 32.56 37.98 M-NPs 103.35 100.77 99.68 95.68 % −3.60 −3.71 −2.61 −9.15 V + M-NPs 122.33b 126.68a 130.68a 131.65a % 14.10 21.05 27.68 25.00 Glucose . 3 Day . 7 Day . 11 Day . 15 Day . Control % 97.5 98.21 96.21 95.36 V 100.32 99.32 105.32 110.12a % 2.89 1.13 9.47 15.48 M-NPs 97.7 98.41 96.41 95.56 % 0.21 0.20 0.21 0.21 V + M-NPs 97.11 96.11 102.11 106.91a % −0.40 −2.14 6.13 12.11 Chol. 3 Day 7 Day 11 Day 15 Day Control 132.25 133.22 129.21 128.25 V 144.55 151.35a 159.33a 165.32a % 9.30 13.61 23.31 28.90 M-NPs 130.45 131.26 127.59 121.36 % −1.36 −1.47 −1.25 −5.37 V + M-NPs 137.89 139.33 145.68a 155.24a % 4.26 4.59 12.75 21.04 Trig. 3 Day 7 Day 11 Day 15 Day Control 107.21 104.65 102.35 105.32 V 110.25 124.98a 135.68a 145.32a % 2.84 19.43 32.56 37.98 M-NPs 103.35 100.77 99.68 95.68 % −3.60 −3.71 −2.61 −9.15 V + M-NPs 122.33b 126.68a 130.68a 131.65a % 14.10 21.05 27.68 25.00 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05. Open in new tab Table 2 Effect of 5% M-NPs IP on glucose, chol. and trig. in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals Glucose . 3 Day . 7 Day . 11 Day . 15 Day . Control % 97.5 98.21 96.21 95.36 V 100.32 99.32 105.32 110.12a % 2.89 1.13 9.47 15.48 M-NPs 97.7 98.41 96.41 95.56 % 0.21 0.20 0.21 0.21 V + M-NPs 97.11 96.11 102.11 106.91a % −0.40 −2.14 6.13 12.11 Chol. 3 Day 7 Day 11 Day 15 Day Control 132.25 133.22 129.21 128.25 V 144.55 151.35a 159.33a 165.32a % 9.30 13.61 23.31 28.90 M-NPs 130.45 131.26 127.59 121.36 % −1.36 −1.47 −1.25 −5.37 V + M-NPs 137.89 139.33 145.68a 155.24a % 4.26 4.59 12.75 21.04 Trig. 3 Day 7 Day 11 Day 15 Day Control 107.21 104.65 102.35 105.32 V 110.25 124.98a 135.68a 145.32a % 2.84 19.43 32.56 37.98 M-NPs 103.35 100.77 99.68 95.68 % −3.60 −3.71 −2.61 −9.15 V + M-NPs 122.33b 126.68a 130.68a 131.65a % 14.10 21.05 27.68 25.00 Glucose . 3 Day . 7 Day . 11 Day . 15 Day . Control % 97.5 98.21 96.21 95.36 V 100.32 99.32 105.32 110.12a % 2.89 1.13 9.47 15.48 M-NPs 97.7 98.41 96.41 95.56 % 0.21 0.20 0.21 0.21 V + M-NPs 97.11 96.11 102.11 106.91a % −0.40 −2.14 6.13 12.11 Chol. 3 Day 7 Day 11 Day 15 Day Control 132.25 133.22 129.21 128.25 V 144.55 151.35a 159.33a 165.32a % 9.30 13.61 23.31 28.90 M-NPs 130.45 131.26 127.59 121.36 % −1.36 −1.47 −1.25 −5.37 V + M-NPs 137.89 139.33 145.68a 155.24a % 4.26 4.59 12.75 21.04 Trig. 3 Day 7 Day 11 Day 15 Day Control 107.21 104.65 102.35 105.32 V 110.25 124.98a 135.68a 145.32a % 2.84 19.43 32.56 37.98 M-NPs 103.35 100.77 99.68 95.68 % −3.60 −3.71 −2.61 −9.15 V + M-NPs 122.33b 126.68a 130.68a 131.65a % 14.10 21.05 27.68 25.00 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05. Open in new tab Table 3 Effect of 5% M-NPs IP on liver functions in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals AST . 3 Day . 7 Day . 11 Day . 15 Day . control 101 105 110 102 V 109 115 130a 135a % 7.92 9.52 18.18 32.35 M-NPs 98 102 100 99 % −2.97 −2.86 −9.09 −2.94 V + M-NPs 100 105 110b 120a,b % −0.99 0.00 0.00 17.65 ALT 3 Day 7 Day 11 Day 15 Day control 53 52 54 55 V 57 55 58 62a % 7.55 5.77 7.41 12.73 M-NPs 51 49 48 52 % −3.77 −5.77 −11.11 −5.45 V + M-NPs 50b 51 52 52b % −5.66 −1.92 −3.70 −5.45 ALP 3 Day 7 Day 11 Day 15 Day control 59.32 60.11 58.65 57.36 V 77.21a 80.35a 95.66a 111.23a % 30.1 33.67 63.10 93.9 M-NPs 60.32 61.23 59.36 60.35 % 1.96 1.86 1.21 5.21 V + M-NPs 65.32b 64.36a,b 68.55a,b 70.26a,b % 10.1 7.07 16.88 22.4 Bil 3 Day 7 Day 11 Day 15 Day control 0.54 0.49 0.52 0.54 V 0.59a 0.65a 0.94a 1.85a % 9.26 32.65 80.77 242.59 M-NPs 0.55 0.49 0.58 0.57 % 1.85 0.00 11.54 5.56 V + M-NPs 0.51b 0.53b 0.57b 0.55b % −5.56 8.16 9.62 1.85 AST . 3 Day . 7 Day . 11 Day . 15 Day . control 101 105 110 102 V 109 115 130a 135a % 7.92 9.52 18.18 32.35 M-NPs 98 102 100 99 % −2.97 −2.86 −9.09 −2.94 V + M-NPs 100 105 110b 120a,b % −0.99 0.00 0.00 17.65 ALT 3 Day 7 Day 11 Day 15 Day control 53 52 54 55 V 57 55 58 62a % 7.55 5.77 7.41 12.73 M-NPs 51 49 48 52 % −3.77 −5.77 −11.11 −5.45 V + M-NPs 50b 51 52 52b % −5.66 −1.92 −3.70 −5.45 ALP 3 Day 7 Day 11 Day 15 Day control 59.32 60.11 58.65 57.36 V 77.21a 80.35a 95.66a 111.23a % 30.1 33.67 63.10 93.9 M-NPs 60.32 61.23 59.36 60.35 % 1.96 1.86 1.21 5.21 V + M-NPs 65.32b 64.36a,b 68.55a,b 70.26a,b % 10.1 7.07 16.88 22.4 Bil 3 Day 7 Day 11 Day 15 Day control 0.54 0.49 0.52 0.54 V 0.59a 0.65a 0.94a 1.85a % 9.26 32.65 80.77 242.59 M-NPs 0.55 0.49 0.58 0.57 % 1.85 0.00 11.54 5.56 V + M-NPs 0.51b 0.53b 0.57b 0.55b % −5.56 8.16 9.62 1.85 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05 Open in new tab Table 3 Effect of 5% M-NPs IP on liver functions in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals AST . 3 Day . 7 Day . 11 Day . 15 Day . control 101 105 110 102 V 109 115 130a 135a % 7.92 9.52 18.18 32.35 M-NPs 98 102 100 99 % −2.97 −2.86 −9.09 −2.94 V + M-NPs 100 105 110b 120a,b % −0.99 0.00 0.00 17.65 ALT 3 Day 7 Day 11 Day 15 Day control 53 52 54 55 V 57 55 58 62a % 7.55 5.77 7.41 12.73 M-NPs 51 49 48 52 % −3.77 −5.77 −11.11 −5.45 V + M-NPs 50b 51 52 52b % −5.66 −1.92 −3.70 −5.45 ALP 3 Day 7 Day 11 Day 15 Day control 59.32 60.11 58.65 57.36 V 77.21a 80.35a 95.66a 111.23a % 30.1 33.67 63.10 93.9 M-NPs 60.32 61.23 59.36 60.35 % 1.96 1.86 1.21 5.21 V + M-NPs 65.32b 64.36a,b 68.55a,b 70.26a,b % 10.1 7.07 16.88 22.4 Bil 3 Day 7 Day 11 Day 15 Day control 0.54 0.49 0.52 0.54 V 0.59a 0.65a 0.94a 1.85a % 9.26 32.65 80.77 242.59 M-NPs 0.55 0.49 0.58 0.57 % 1.85 0.00 11.54 5.56 V + M-NPs 0.51b 0.53b 0.57b 0.55b % −5.56 8.16 9.62 1.85 AST . 3 Day . 7 Day . 11 Day . 15 Day . control 101 105 110 102 V 109 115 130a 135a % 7.92 9.52 18.18 32.35 M-NPs 98 102 100 99 % −2.97 −2.86 −9.09 −2.94 V + M-NPs 100 105 110b 120a,b % −0.99 0.00 0.00 17.65 ALT 3 Day 7 Day 11 Day 15 Day control 53 52 54 55 V 57 55 58 62a % 7.55 5.77 7.41 12.73 M-NPs 51 49 48 52 % −3.77 −5.77 −11.11 −5.45 V + M-NPs 50b 51 52 52b % −5.66 −1.92 −3.70 −5.45 ALP 3 Day 7 Day 11 Day 15 Day control 59.32 60.11 58.65 57.36 V 77.21a 80.35a 95.66a 111.23a % 30.1 33.67 63.10 93.9 M-NPs 60.32 61.23 59.36 60.35 % 1.96 1.86 1.21 5.21 V + M-NPs 65.32b 64.36a,b 68.55a,b 70.26a,b % 10.1 7.07 16.88 22.4 Bil 3 Day 7 Day 11 Day 15 Day control 0.54 0.49 0.52 0.54 V 0.59a 0.65a 0.94a 1.85a % 9.26 32.65 80.77 242.59 M-NPs 0.55 0.49 0.58 0.57 % 1.85 0.00 11.54 5.56 V + M-NPs 0.51b 0.53b 0.57b 0.55b % −5.56 8.16 9.62 1.85 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05 Open in new tab A significant change was only observed on the V group on the 11th and 15th days of administration versus control value. A significant decrease was observed on the last two decapitations (11 and 15 days) for AST and only on the 15th day for ALT, while in ALK and Bil, the sign was observed throughout the experimental period as comparing the V + M-NPs group with its corresponding in V group (Table 3). A significant increase in urea level was observed on the last three decapitations in both V and V + M-NPs groups in comparison to control results, oppositely, urea level showed a significant decrease on the 15th day of M-NPs IP injection. In concerning to creatinine level, a significant increase was observed starting from the first decapitation in both V and V + M-NPs groups and continued till the end of the experiment versus control, while for M-NPs group, creat showed a non-significant change as compared to the control level (Table 4). Table 4 Effect of 5% M-NPs IP on kidney functions in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals Urea . 3 Day . 7 Day . 11 Day . 15 Day . Control 36.21 33.22 34.59 35.84 V 39.33 42.68a 49.86a 55.69a % 8.62 28.48 44.15 55.39 M-NPs 36.11 34.52 31.24 30.21a % −0.28 3.91 −9.68 −15.71 V + M-NPs 40.21 42.21a 43.26a,b 49.51a % 11.05 27.06 25.07 38.14 Creat 3 Day 7 Day 11 Day 15 Day control 0.52 0.51 0.53 0.49 V 0.64a 0.68a 0.77a 0.92a % 23.08 33.33 45.28 87.76 M-NPs 0.5 0.48 0.49 0.48 % −3.85 −5.88 −7.55 −2.04 V + M-NPs 0.59a 0.61a 0.69a 0.75a,b % 13.46 19.61 30.16 53.06 Uricacid 3 Day 7 Day 11 Day 15 Day control 0.51 0.5 0.56 0.5 V 0.55 0.59a 0.85a 0.97a % 7.84 18.00 51.79 94.00 M-NPs 0.51 0.52 0.49a 0.44a % 0.00 4.00 −12.50 −12.00 V + M-NPs 0.52 0.53a 0.66a,b 0.73a,b % 1.92 6.00 17.87 46.00 Urea . 3 Day . 7 Day . 11 Day . 15 Day . Control 36.21 33.22 34.59 35.84 V 39.33 42.68a 49.86a 55.69a % 8.62 28.48 44.15 55.39 M-NPs 36.11 34.52 31.24 30.21a % −0.28 3.91 −9.68 −15.71 V + M-NPs 40.21 42.21a 43.26a,b 49.51a % 11.05 27.06 25.07 38.14 Creat 3 Day 7 Day 11 Day 15 Day control 0.52 0.51 0.53 0.49 V 0.64a 0.68a 0.77a 0.92a % 23.08 33.33 45.28 87.76 M-NPs 0.5 0.48 0.49 0.48 % −3.85 −5.88 −7.55 −2.04 V + M-NPs 0.59a 0.61a 0.69a 0.75a,b % 13.46 19.61 30.16 53.06 Uricacid 3 Day 7 Day 11 Day 15 Day control 0.51 0.5 0.56 0.5 V 0.55 0.59a 0.85a 0.97a % 7.84 18.00 51.79 94.00 M-NPs 0.51 0.52 0.49a 0.44a % 0.00 4.00 −12.50 −12.00 V + M-NPs 0.52 0.53a 0.66a,b 0.73a,b % 1.92 6.00 17.87 46.00 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05. Open in new tab Table 4 Effect of 5% M-NPs IP on kidney functions in adult male albino rats intoxicated with AM.V (20 mg/kg b.wt.) at different time intervals Urea . 3 Day . 7 Day . 11 Day . 15 Day . Control 36.21 33.22 34.59 35.84 V 39.33 42.68a 49.86a 55.69a % 8.62 28.48 44.15 55.39 M-NPs 36.11 34.52 31.24 30.21a % −0.28 3.91 −9.68 −15.71 V + M-NPs 40.21 42.21a 43.26a,b 49.51a % 11.05 27.06 25.07 38.14 Creat 3 Day 7 Day 11 Day 15 Day control 0.52 0.51 0.53 0.49 V 0.64a 0.68a 0.77a 0.92a % 23.08 33.33 45.28 87.76 M-NPs 0.5 0.48 0.49 0.48 % −3.85 −5.88 −7.55 −2.04 V + M-NPs 0.59a 0.61a 0.69a 0.75a,b % 13.46 19.61 30.16 53.06 Uricacid 3 Day 7 Day 11 Day 15 Day control 0.51 0.5 0.56 0.5 V 0.55 0.59a 0.85a 0.97a % 7.84 18.00 51.79 94.00 M-NPs 0.51 0.52 0.49a 0.44a % 0.00 4.00 −12.50 −12.00 V + M-NPs 0.52 0.53a 0.66a,b 0.73a,b % 1.92 6.00 17.87 46.00 Urea . 3 Day . 7 Day . 11 Day . 15 Day . Control 36.21 33.22 34.59 35.84 V 39.33 42.68a 49.86a 55.69a % 8.62 28.48 44.15 55.39 M-NPs 36.11 34.52 31.24 30.21a % −0.28 3.91 −9.68 −15.71 V + M-NPs 40.21 42.21a 43.26a,b 49.51a % 11.05 27.06 25.07 38.14 Creat 3 Day 7 Day 11 Day 15 Day control 0.52 0.51 0.53 0.49 V 0.64a 0.68a 0.77a 0.92a % 23.08 33.33 45.28 87.76 M-NPs 0.5 0.48 0.49 0.48 % −3.85 −5.88 −7.55 −2.04 V + M-NPs 0.59a 0.61a 0.69a 0.75a,b % 13.46 19.61 30.16 53.06 Uricacid 3 Day 7 Day 11 Day 15 Day control 0.51 0.5 0.56 0.5 V 0.55 0.59a 0.85a 0.97a % 7.84 18.00 51.79 94.00 M-NPs 0.51 0.52 0.49a 0.44a % 0.00 4.00 −12.50 −12.00 V + M-NPs 0.52 0.53a 0.66a,b 0.73a,b % 1.92 6.00 17.87 46.00 aSignificant to control. bSignificant to V. n = 6, significant change at P < 0.05. Open in new tab Uric acid showed a significant increase after vanadium administration reaching to duplicate the control value on the 15th day, also, in the V + M-NPs group, a significant increase was noticed on the uric acid level. M-NPs administration resulted in a non-significant change all over the treatment period. In comparing V + M-NPs with V group, uric acid showed a significant decrease in the 11th and 15th days of the experiment (Table 4). Discussion The daily orally administration of vanadium in the present study showed the capability of vanadium to be absorbed in the blood then distribute and accumulate in the different body organs that ordered as kidney > liver > testes > brain > spleen > lung > heart. This finding is coming in agreement with many other studies that proved the ability of vanadium to accumulate in the body organs [55–57]. On the other hand, M-NPs IP injection in parallel with vanadium administration induced a significant decrease in vanadium contents in the organ’s tissues, this may be regarded to the complexation and/or the electrostatic interaction or chelating properties between the adsorbent (M-NPs) and the adsorbate species (vanadium) [58]. In concern to the hematological parameter, Vanadium has the ability to crosses the cell membrane of erythrocytes via anion channels, then it binds to the phosphate-binding site of (Na, K)-ATPase on the cytoplasmic side of the membrane [59], which may produce a deformability of erythrocytes and a per-oxidative changes in erythrocytes membrane leading to its hemolysis [60]. So the observed depletion in the RBCs and the Hb content which resulted in the present study may be due to the hemolysis produced from vanadium interaction. With regarding the liver function, the detoxication machine in the body, there was an observed elevation in the liver enzymes where, the elevation in ALT indicates hepatocellular damage, AST indicates liver damage, hepatitis, as well as a cardiac infarction and muscle injury [61]. ALP, its adjustment the layer penetrability, expanded ALP level is often related to a different issue, for example, extrahepatic bile obstacle, intrahepatic cholestasis, infiltrative liver ailment, just as hepatitis and bone ailment its alteration is probably going to influence the membrane permeability, increased ALP level is often associated with a different issue, for example, extrahepatic bile obstruction, intrahepatic cholestasis, infiltrative liver disease, hepatitis and bone disease [62]. The accumulation of vanadium in liver and kidney lead to a self-defense mechanism by producing macrophage inflammatory proteins (MIP-2) from both organs [63], this defense mechanism is mediated by the generated reactive oxygen species through vanadium accumulation [64]. Thus, reactive oxygen spices are involved in the inflammation and stress responses through activation of transcriptional factors. Furthermore, after the exposure to high dose of vanadium organs damage and metabolism alteration were observed, which may attribute in part to the detoxification mechanism of metals through glutathione conjugation and to the damage of mitochondria which released the cytochrome ‘c,’ that activates the caspases-3 and -8 leading to provoke further mitochondrial damage and activating cellular substrates such as poly(ADP-ribose)-polymerase (PARP), leading to apoptosis of organ cells [65]. Organs like liver and kidney get necrotized in heavy metal exposition and due to this narcotization, synthesized chol. and lipids within tissue get mobilized into the bloodstream and cause an increased concentration of chol. and lipids in serum [66]. Creatinine and blood urea nitrogen are two parameters that could give an idea on the kidney normal functioning and also on the effect of vanadium on the tubular and or glomerulus part of the kidney. The present experiment illustrated the increment in the level of creatinine and blood urea nitrogen in adult male albino rats. Vanadium may function as a cellular regulator of Na+/K + ATPase in vivo, these sodium pumps are found in a high concentration in kidney tubules, so vanadium could depress tubular reabsorption in proximal and distal nephron segments by inhibition of Na+/K + ATPase activity [67]. Generally, V3+ and V4+ predominate in body tissues while V5+ predominates in plasma. In the case of oral ingestion, vanadium compounds are exposed to acidic solutions in the stomach (at which the predominate form of vanadium is VO2+). At physiological, pH vanadium compounds have been shown to exist in monomeric tetravalent [VO(OH)3]− and dimeric [(VO)2(OH)5]− forms, as well as pentavalent (H2VO4−) are the predominant forms of vanadium. So, at pH < 3.5 cationic vanadium species are predominant as the vanadyl cation VO2+, while at pH 3.5–9, Polynuclear anionic species of vanadium are predominant (Fig. 6) [68]. Figure 6 Open in new tabDownload slide Vanadium speciation as a function of pH. Figure 6 Open in new tabDownload slide Vanadium speciation as a function of pH. On the other hand, cobalt manganese ferrite NPs may carry a net positive or negative charge depending upon the pH of the media and the pH of the point of zero charges (pHpzc) (Fig.7). Figure 7 Open in new tabDownload slide Point of zero charge of Co0.5Mn0.5Fe2O4. Figure 7 Open in new tabDownload slide Point of zero charge of Co0.5Mn0.5Fe2O4. If the pH of the media is lower than the pHpzc, the surfaces of the NPs will collect net positive charge and vice versa. Therefore, there will be either electrostatic attraction or repulsion between the cobalt manganese ferrite NPs surface and vanadium species depending on the pH of the media. The obtained pHpzc value was 5.8, indicating that the cobalt manganese ferrite surface carried a net positive charge. Accordingly, the suggested mechanism of interaction between vanadium and cobalt manganese ferrite NPs is an electrostatic attraction (between the positive surfaces of the NPs and negatively charged species of vanadium) [69–73]. Based on the results, anionic species of vanadium are adsorbed on the M-NPs that may occur via electrostatic attraction between positively charged M-NPs and negatively charged vanadate species. The daily IP injection of Mn Co ferromagnetic nanoparticles (M-NPs) showed a significant increase in Hb% and HCT, and a significant decrease in urea and uric acid, and a non-significant change in glucose, AST, ALT, ALk. Ph, Bil, Chol., Trig., creat. and RBCs. This effect may be regarded as the essentiality of the three metals involved in the preparation of the NPs materials. Manganese is an essential metal that involved in various physiological functions as a cofactor for numerous enzymes and in superoxide dismutase (as a defense against superoxide-induced oxidative stress) [46–51]. The majority and essentiality of cobalt in humans come from its role in cobalamin and vitamin B, which have a major impact on human health [52]. The last important essential metal involved in the used M-NPs in the present study is iron. Many vital compounds in the human are depending on iron in its formation (Hb, myoglobin, cytochromes, cytochrome oxidase, peroxidase, catalase and the metalloflavoprotein enzymes, including xanthine oxidase and the mitochondrial enzyme α-glycerophosphate oxidase) improving human health. Conclusion Vanadium which used in various industrial applications might lead to pathological and irreversible damage effects in tissues and organs. The present study investigates the role of MNPs to attenuate the different physiological hazards effects induced by Am.V. The synthesized M-NPs were characterized by the XRD, EDX, FTIR), DLS and zeta potential techniques. Vanadium was distribute and accumulate in the different body organs (kidney > liver > lung > brain > spleen). Also, it induces a significant disturbance in many physiological parameters (RBS, chol, trig, …, etc.). The IP administration of MNPs, in parallel with Am.V, showed the ability of MNPs to reduce Am.V hazardous effects. Cobalt manganese ferrite NPs could ameliorate Am.V’s hazardous effects. Compliance with Ethical Standards The investigation protocol was approved by the ethics committee of nuclear material authority, which is performed in accordance with the ethical standards laid down in the US guidelines (NIH Publication no. 85–23, amended in 1985). 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Secondary transporters for nickel and cobalt ions: theme and variations . Biometals 2005 ; 18 : 399 – 405 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) TI - The influence of cobalt manganese ferrite nanoparticles (Co0.5Mn0.5Fe2O4) on reduction of hazardous effects of vanadate in adult rats JF - Toxicology Research DO - 10.1093/toxres/tfaa007 DA - 2020-05-08 UR - https://www.deepdyve.com/lp/oxford-university-press/the-influence-of-cobalt-manganese-ferrite-nanoparticles-co0-5mn0-LGyozlw3RO SP - 81 EP - 90 VL - 9 IS - 2 DP - DeepDyve ER -