Synthesis and Biological Evaluations of a Novel Oxidovanadium ( IV ) Adenosine Monophosphate Complex as Anti-Diabetic Agent

In the present study, a novel [(AMP)(VO)(H2O)2] complex was formed through chemical reactions between oxidovanadium(IV)sulfate and adenosine monophosphate. This complex was characterized using various analyses, including microanalytical, molar conductivity, spectroscopic (solid reflectance and FTIR), magnetic susceptibility, thermogravimetric (TGA), X-ray powder diffraction (XRD), and scanning (SEM) and transmission (TEM) electron microscopy. The in vivo antidiabetic activity of the oxidovanadium(IV) complex was determined using streptozotocin-induced rats. The results suggested that the synthesized complex can be used as an antidiabetic agent based on the observed biochemical effects.


Introduction
A number of potential pharmaceutical agents contain metal-binding sites, which can bind or interact with metal ions and may affect their vital activities [1].Some vanadium compounds have insulin-mimetic properties that are involved in the maintenance of some active metabolic pathways regulated by insulin, through its binding with receptors [2].Vanadium metal ions have insulin-like effects in both liver and adipose tissues [3] and also improve hepatic and insulin sensitivity [4]; therefore, vanadium can potentially be used to treat both types of diabetes.Potent vanadium complexes with various coordination modes and their structure-function relationship have been studied using both in vivo and in vitro approaches [5,6].Adenosine monophosphate (AMP; Figure 1) plays an essential role as an allosteric effector in the regulation of carbohydrate metabolism [13][14][15][16].Myocardial 5'-AMP catabolism was studied by Headrick et al. (2001) in perfused guinea pigs, rats, and mice [17,18].Herein, the current study explores the synthesis, structure elucidation, and antidiabetic effects of a novel oxidovanadium(IV)--AMP complex.

Chemicals and Reagents
All chemicals in this article were received from Sigma-Aldrich chemical company (St.Louis, MI, United States) with pure grade.

Synthesis of Oxidovanadium(IV)-AMP Complex
The [(AMP)(VO)(H2O)2] complex was synthesized through the reaction between VOSO4•H2O (0.181 g, 1.0 mmol) and AMP (0.347 g, 1.0 mmol) in 40 mL of CH3OH/H2O (50/50 (v/v)) mixed solvent.The reaction mixture was adjusted to a pH of 8.5 using 5% NH3standard solution.The chemical reaction was refluxed at ~60 °C for 30 min until the precipitate settled.It was filtered, washed several times by minimal amounts of hot methanol, dried, and then stored in a vacuum desiccator.

Instruments and Methods
 Elemental analyses were performed using PerkinElmer model CHN 2400. Vanadium metal percentage was calculated gravimetrically as vanadium oxide. Molar conductivity of oxidovanadium(IV)-AMP complex was measured using a conductivity meter model Jenway4010 at 1.0 × 10 −3 mol/cm 3 concentration in DMSO solvent. Solid reflectance spectra were scanned using UV-Vis Spectrophotometer model UV-3101 PC.  FTIR spectra were performed on a Bruker FTIR spectrophotometer. Magnetic data were collected based on a magnetic susceptibility balance. TGA/DTG curves were scanned depending on the thermogravimetric analyzer model Shimadzu-50Hunder nitrogen atmosphere. SEM images were acquired using a Quanta 250 FEG microscope. TEM images were acquired using JEOL 100S microscope. XRD were recorded on the X'Pert PRO PANalytical.

Chemicals and Reagents
All chemicals in this article were received from Sigma-Aldrich Chemical Company (St. Louis, MI, USA) with pure grade.

Synthesis of Oxidovanadium(IV)-AMP Complex
The [(AMP)(VO)(H 2 O) 2 ] complex was synthesized through the reaction between VOSO 4 •H 2 O (0.181 g, 1.0 mmol) and AMP (0.347 g, 1.0 mmol) in 40 mL of CH 3 OH/H 2 O (50/50 (v/v)) mixed solvent.The reaction mixture was adjusted to a pH of 8.5 using 5% NH 3 standard solution.The chemical reaction was refluxed at ~60 • C for 30 min until the precipitate settled.It was filtered, washed several times by minimal amounts of hot methanol, dried, and then stored in a vacuum desiccator.

Instruments and Methods
Elemental analyses were performed using PerkinElmer model CHN 2400.Vanadium metal percentage was calculated gravimetrically as vanadium oxide.Molar conductivity of oxidovanadium(IV)-AMP complex was measured using a conductivity meter model Jenway4010 at 1.0 × 10 −3 mol/cm 3 concentration in DMSO solvent.Solid reflectance spectra were scanned using UV-Vis Spectrophotometer model UV-3101 PC.FTIR spectra were performed on a Bruker FTIR spectrophotometer.Magnetic data were collected based on a magnetic susceptibility balance.TGA/DTG curves were scanned depending on the thermogravimetric analyzer model Shimadzu-50Hunder nitrogen atmosphere.SEM images were acquired using a Quanta 250 FEG microscope.TEM images were acquired using JEOL 100S microscope.XRD were recorded on the X'Pert PRO PANalytical.

In Vivo Experimental Design
The animals (male albino rats, weight 100-120 g) were classified into four groups of 10 animals per group.
Group I: untreated negative control.

Electronic and Magnetic Measurements
The electronic spectrum of the oxidovanadium(IV)-AMP complex revealed distinguishable bands of oxidovanadium(IV) in a square pyramidal geometry.The absorption bands around 795 and 626 nm were respectively assigned to 2 B 2 → 2 E and 2 B 2 → 2 B 1 electronic transitions [26].The weak bands around 530 and 425 nm were assigned to L−M CT charge transfer.The experimental magnetic moment of the oxidovanadium(IV)-AMP complex was 2.02 BM, due to the square pyramidal oxidovanadium(IV)geometry [26,27].

Infrared Spectra
The infrared spectra of the oxidovanadium(IV)-AMP complex and 5 -AMP were determined in order to elucidate the bonding mechanism responsible for complex formation.The spectra of the complex and its free ligand were similar but there were some differences, suggestive of the following coordination dynamics: (1) In the comparison between free AMP ligand and the oxidovanadium(IV)-AMP complex, the shifts in bands observed between 4000 and 1700 cm −1 were attributed to the rearrangement of the hydrogen bonding network upon complex formation [28].
(2) Free 5 -AMP showed a strong absorption band at 1641 cm −1 that was mainly attributed to the bending (scissoring) of NH 2 [29].In the oxidovanadium(IV)-AMP complex, the intensity of this band changed slightly, but its position was not affected (1648 cm −1 ).This observation allowed for the exclusion of any coordination through the NH 2 group, as the metalation-deprotonation mechanism required for the metal-NH 2 interaction would cause a shift or disappearance in the absorption frequencies [28].The small shift in intensity was due to the replacement of intramolecular hydrogen bonds of the NH 2 to the phosphate group in the 5 -AMP, with stronger hydrogen bonds of the complexed H 2 O molecule [29].
(3) The stretching vibration bands within 3400-2700 cm −1 and 1400-400 cm −1 [28] were assigned to the sugar vibrational frequencies of 5 -AMP, and the presence of weak absorption bands at 900-800 cm −1 were due to the frequencies of sugar phosphate vibrations [28].These bands were affected upon the complexation, through the phosphate group [28].
(4) Absorption bands of the phosphate group were found at 1104, 983, and 813 cm −1 , due to PO 3 asymmetric, PO 3 symmetric, and P-O stretching vibrations, respectively [29].Comparing these bands to those of the oxidovanadium(IV)-AMP complex revealed similar positioning but clear changes in intensity, particularly in PO 3 symmetric and P-O stretching vibration, while the PO 3 asymmetric vibration was less affected due to the overlap with the ν(V = O) peak.These data are consistent with the coordination of the metal ion occurring through deprotonation of the phosphate group [28].
(5) In the case of complexation, the absorption bands within the 3300-3000 cm −l range are likely due to ν(OH) of the coordinated molecules [29], and this was further supported by the presence of bands at ~800 cm −l due to the rocking vibration motion δ r (H 2 O) of the coordinated H 2 O molecules [28].
(6) After complexation, the strong band at 1114 cm −1 was assigned to ν(V = O) stretching vibration, as expected from data published on oxidovanadium(IV) complexes [28].(7) In case of oxidovanadium(IV)-AMP complex, a new band was observed at 520 cm −1 that was assigned to the ν(M-O) of the M-OH 2 bond [29].
The analytical and spectroscopic data conformed to the stoichiometric formulations proposed in Figure 2.
Crystals 2019, 9, x FOR PEER REVIEW 5 of 13 bands at ~800 cm −l due to the rocking vibration motion δr (H2O) of the coordinated H2Omolecules [28].(6) After complexation, the strong band at 1114 cm −1 was assigned to ν(V = O) stretching vibration, as expected from data published on oxidovanadium(IV) complexes [28].(7) In case of oxidovanadium(IV)-AMP complex, a new band was observed at 520 cm −1 that was assigned to the ν(M-O) of the M-OH2 bond [29].
The analytical and spectroscopic data conformed to the stoichiometric formulations proposed in Figure 2.
Proposed structure of the oxidovanadium(IV)-AMP complex.

Thermal and Kinetic Studies
The TG curve of the [(AMP)(VO)(H2O)2] complex was redrawn as the mass loss against temperature, and the DTA curve was redrawn as the rate of mass loss against temperature under a nitrogen gas environment.The thermal decomposition curves (TG/DTG and DTA) are given in Figures 3 and 4, and the thermoanalytical data are listed in Table 1.The thermal decomposition of the oxidovanadium(IV)-AMP complex occurred in two steps.The first degradation step occurred at 27-392 °C, DTGmax = 254 °C, and DTA = 74 and 265 °C (exo), which corresponded to the loss of C4H6N2O2 (organic moiety), reflected by an observed 25.62% reduction in mass (calculated = 25.44%).The second step occurred between 393 and 714 °C, DTGmax = 635 °C, and DTA = 517 °C (endo) due to the loss of C6H10N3O6P and the mass associated with this organic moiety (observed = 55.49%,calculated = 56.02%).VO2oxide was the final residue at 800 °C.
In Table 2, the kinetic-thermodynamic parameters ΔE*, ΔS*, ΔH*, and ΔG* of the [(AMP)(VO)(H2O)2]complex were calculated dependent on the Coats-Redfern and Horowitz-Metzger relations [30,31].Some important results were deduced from the kinetic-thermodynamic parameters, as follows:  The [(AMP)(VO)(H2O)2] complex had a high thermal stability according to high activation energy. The negative value of the oxidovanadium(IV)-AMP complex gave an impression of a more ordered, rather than free, AMP ligand.

Thermal and Kinetic Studies
The TG curve of the [(AMP)(VO)(H 2 O) 2 ] complex was redrawn as the mass loss against temperature, and the DTA curve was redrawn as the rate of mass loss against temperature under a nitrogen gas environment.The thermal decomposition curves (TG/DTG and DTA) are given in Figures 3 and 4, and the thermoanalytical data are listed in Table 1 In Table 2, the kinetic-thermodynamic parameters ∆E*, ∆S*, ∆H*, and ∆G* of the [(AMP)(VO)(H 2 O) 2 ] complex were calculated dependent on the Coats-Redfern and Horowitz-Metzger relations [30,31].Some important results were deduced from the kinetic-thermodynamic parameters, as follows: The [(AMP)(VO)(H 2 O) 2 ] complex had a high thermal stability according to high activation energy.The negative value of the oxidovanadium(IV)-AMP complex gave an impression of a more ordered, rather than free, AMP ligand., SEM, and TEM.The XRD analysis showed that the oxidovanadium(IV)-AMP complex was pure and had good crystallinity, as no peak characteristics of impurities were observed.The Scherrer equation [32,33] was employed to determine the particle size of oxidovanadium(IV)-AMP complex at the highest diffraction peak (2θ = 20.43 • ) (Figure 5).XRD patterns revealed the nanocrystalline (20 nm) nature of the oxidovanadium(IV)-AMP complex.
SEM and TEM analyses gave information concerning the particle size and surface morphology of the isolated solid [(AMP)(VO)(H 2 O) 2 ] complex.The SEM and TEM images revealed that the solid complex aggregated into different grain sizes, with a narrow size distribution that averaged around 20 nm.The SEM micrographs at different magnifications showed that the oxidovanadium(IV)-AMP complexes were organized into regular slices and arranged into stone structures with no well-defined particles (Figure 6a).Increasing the magnification did not provide better particle resolution (Figure 6a).According to the TEM images, the particles of the [(AMP)(VO)(H 2 O) 2 ] complex were irregularly shaped, and their size was widely distributed around 20 nm (Figure 6b).4-80°, SEM, and TEM.The XRD analysis showed that the oxidovanadium(IV)-AMP complex was pure and had good crystallinity, as no peak characteristics of impurities were observed.The Scherrer equation [32,33] was employed to determine the particle size of oxidovanadium(IV)-AMP complex at the highest diffraction peak (2θ = 20.43°)(Figure 5).XRD patterns revealed the nanocrystalline (20 nm) nature of the oxidovanadium(IV)-AMP complex.SEM and TEM analyses gave information concerning the particle size and surface morphology of the isolated solid [(AMP)(VO)(H2O)2] complex.The SEM and TEM images revealed that the solid complex aggregated into different grain sizes, with a narrow size distribution that averaged around20 nm.The SEM micrographs at different magnifications showed that the oxidovanadium(IV)-AMP complexes were organized into regular slices and arranged into stone structures with no well-defined particles(Figure 6a).Increasing the magnification did not provide better particle resolution (Figure 6a).According to the TEM images, the particles of the [(AMP)(VO)(H2O)2] complex were irregularly shaped, and their size was widely distributed around 20nm (Figure 6b).SEM and TEM analyses gave information concerning the particle size and surface morphology of the isolated solid [(AMP)(VO)(H2O)2] complex.The SEM and TEM images revealed that the solid complex aggregated into different grain sizes, with a narrow size distribution that averaged around20 nm.The SEM micrographs at different magnifications showed that the oxidovanadium(IV)-AMP complexes were organized into regular slices and arranged into stone structures with no well-defined particles(Figure 6a).Increasing the magnification did not provide better particle resolution (Figure 6a).According to the TEM images, the particles of the [(AMP)(VO)(H2O)2] complex were irregularly shaped, and their size was widely distributed around 20nm (Figure 6b).

Blood Glucose and Insulin Levels
In Table 3, both Group III and Group IV showed significantly decreased blood glucose levels relative to the positive control Group II.This effect was clearer for the oxidovanadium(IV)-AMP complex, which decreased blood glucose levels by 31.66%from410.23 ± 14.52 mg/dL in Group II to 280.34 ± 6.87 mg/dL in Group IV, while Group III decreased by 30.88%.STZ treatment significantly reduced the levels of insulin compared to the untreated negative control animals.The administration of oxidovanadium(IV) sulfate and the oxidovanadium(IV)-AMP complex to STZ-treated rats also significantly increased insulin levels compared to the untreated diabetic animals.For Group III, the insulin increased by 42.61% and for Group IV, by 44.64%; thus, these data agree with the reports in the literature that oxidovanadium(IV)compounds can mimic many metabolic activities of insulin both in vivo and in vitro [34,35].

GPT Activity
In Table 3, the GPT enzyme data indicated that Group II was slightly increased by 10.30% from 111.50 ± 7.44 U/L in Group II to 124.31 ± 10.53 U/L in Group III, whereas after the injection of rats by oxidovanadium(IV)-AMP complex (Group IV), the serum GPT activity was decreased to 101.57± 6.33 U/L (8.90%), which was less than Group II, and less than Group III by 18.29%.According to these data, it can be concluded that the oxidovanadium(IV)-AMP complex had a minor effect on the liver cells in comparison with STZ or oxidovanadium(IV) alone, and both had higher levels than Group I (72.33 ± 6.61 U/L) [36].

Creatinine and Uric Acid Levels
According to Table 3, the diabetic rats treated with either oxidovanadium(IV) sulfate alone or the oxidovanadium(IV) complex showed decreased creatinine levels compared to untreated diabetic rats.This was particularly pronounced in Group IV, where the serum creatinine decreased to 0.79 ± 0.14 mg/dL from 1.14 ± 0.18 mg/dL in the Group II.These data indicate that the oxidovanadium(IV) complex had no major effect on the tissue of kidney in vivo, and improved kidney function.
The increased levels of uric acid (hyperuricemia) observed in diabetic rats in this study, compared to the healthy control group, are similar to a previous report [37].Relative to the positive control, uric acid levels decreased by 20.04% with the treatment of the oxidovanadium(IV)-AMP complex and by 19.41% with oxidovanadium(IV) sulfate alone.This reduction can be discussed based on the inhibition of oxidative phosphorylation, which contributed to decreasing protein synthesis [37].

LDH and G6PD Activities
The LDH activity in case of the diabetic rats (Group II) was significantly increased compared with the control group (Group I), as clarified in Table 3.The LDH activity of oxidovanadium(IV)-AMP complex (Group IV) had a 4.34%decrease compared with Group II, whereas the treatment of diabetic rats by oxidovanadium(IV) sulfate itself was increased by 5.78%.This increase in the level of LDH activity was due to the leakage of LDH into the blood because of STZ toxicity on the liver.Our experimental data is in agreement with a previous report [38].
The G6PD level was decreased in the diabetic rats in comparison with Group I (Table 3), similar to observations in previous work survey [39].Through treatment with oxidovanadium(IV)-AMP complex (Group IV), a significant increase of 18.01% was observed relative to Group II, whereas the treatment with oxidovanadium(IV) sulfate itself caused an increase of 14.37%.

Hb Level
From data in Table 3, the Hb levels were decreased in Group II in comparison with Group I. Reduction of Hb and anemia were due to the non-enzymatic glycosyls of red blood cell membranes [40].The Hb level following oxidovanadium(IV)-AMP complex treatment(Group IV) was increased by 13.84% compared to the untreated diabetic group, whereas the treatment with oxidovanadium(IV) sulfate itself (Group III) increased the Hblevel by 9.40%.

SOD Activity
SOD activity is low in diabetes, and this low activity can be due to its degradation or inhibition as a result of increased free radical production [41,42].In this study (Table 3), the SOD activity was significantly decreased in Group II compared with Group I.The SOD activity was decreased by 6.46% in diabetic rats treated with the oxidovanadium(IV) complex, and by 8.83% for the group treated with oxidovanadium(IV) sulfate itself.

TC, TG, HDL-c, and LDL-cLipid Factors
In Table 3, the lipid factors were increased in Group II in comparison with Group I.This result was averse to published data by Bolkent et al. (2005) [1], which referred to reduced serum HDL-c levels in Group II.In our study, the results of the oxidovanadium(IV) complex (Group IV) led to a decrease in TC, TG, and LDL-c lipid factors(38.03%,23.26%, and 26.89%), respectively, while HDL-c levels were increased by 40.78% relative to Group II.In addition, oxidovanadium(IV) compounds may improve hypercholesterolemia status by modulating lipoprotein metabolism, enhancing LDL uptake by increasing LDL receptor expression, and/or by increasing lecithin cholesterol acyltransferase activity [42][43][44].

Histopathology of the Pancreas
In this study, STZ-induced diabetes produced a marked loss in total body mass and the mass of the pancreas.Diabetes is typically associated with loss of mass as the body switches to using fatty acids for energy, instead of glucose, due to insulin deficiencies.The histopathology of the pancreas from the control rats (Group I) showed healthy pancreatic tissue with typically sized islets of Langerhans and surrounded by healthy pancreatic acini (Figure 7a).By contrast, STZ administration (positive control, Group II) caused severe injury to the pancreas, illustrated by a decrease in islet cell numbers and in the diameter of the islets (Figure 7b,c).This destruction and shrinkage of islets corresponded to the reduced insulin levels that are characteristic of diabetes.The administration of oxidovanadium(IV) sulfate alone (Group III) resulted in the expansion of islets and appeared to reduce the overall injury to the pancreas after30 days of treatment (Figure 7d,e).Treatment with the oxidovanadium(IV)-AMP complex seemed to restore healthy histological structure, including rich vascular supply (Figure 7f).This suggests that the oxidovanadium(IV)-AMP complex enables recovery of, or prevents the damage to, the pancreatic tissue caused by STZ-induced diabetes.
Generally, histological examination of the pancreas of diabetic rats showed shrinkage and a reduction in the size and number of islets of Langerhans, while the group treated with oxidovanadium(IV)-AMP complex showed a restoration in the number and size of these islets.The histology consistently showed well-organized islet structure and many insulin-immune reactive cells within the islets of Langerhans of the diabetic rats treated with oxidovanadium(IV) sulfate and its AMP complex.These data suggest that oxidovanadium(IV) is either protective or regenerative, and further studies with different animal models are necessary to distinguish between these two potential mechanisms.
reduction in the size and number of islets of Langerhans, while the group treated with oxidovanadium(IV)-AMP complex showed a restoration in the number and size of these islets.The histology consistently showed well-organized islet structure and many insulin-immune reactive cells within the islets of Langerhans of the diabetic rats treated with oxidovanadium(IV) sulfate and its AMP complex.These data suggest that oxidovanadium(IV) is either protective or regenerative, and further studies with different animal models are necessary to distinguish between these two potential mechanisms.

Histopathology of the Liver
The damage to the liver caused by STZ treatment was clearly visible in the form of a dystrophic central vein, necrotic hepatocytes, and an abundance of inflammatory cells.This in vivo study revealed that compared to the healthy control group (Group I, Figure 8a), the liver tissue from the STZ-induced diabetic rats (Group II) had marked dilatation and congestion of the central vein, large areas of hepatic necrosis, and inflammatory cell invasion (Figure 8b) By contrast, the liver tissue of diabetic rats treated with the oxidovanadium(IV)-AMP complex had healthy histological structures and hepatic parenchyma (Figure 8d).This is reflective of the protective or regenerative effect of the complex, potentially due to its antioxidant properties.These data suggest that treating diabetic patients with the oxidovanadium(IV)-AMP complex could reduce pervasive tissue damage and diminish the complications from liver dysfunction that occur in this complex disease.

Histopathology of the Liver
The damage to the liver caused by STZ treatment was clearly visible in the form of a dystrophic central vein, necrotic hepatocytes, and an abundance of inflammatory cells.This in vivo study revealed that compared to the healthy control group (Group I, Figure 8a), the liver tissue from the STZ-induced diabetic rats (Group II) had marked dilatation and congestion of the central vein, large areas of hepatic necrosis, and inflammatory cell invasion (Figure 8b).By contrast, the liver tissue of diabetic rats treated with the oxidovanadium(IV)-AMP complex had healthy histological structures and hepatic parenchyma (Figure 8d).This is reflective of the protective or regenerative effect of the complex, potentially due to its antioxidant properties.These data suggest that treating diabetic patients with the oxidovanadium(IV)-AMP complex could reduce pervasive tissue damage and diminish the complications from liver dysfunction that occur in this complex disease.
. The thermal decomposition of the oxidovanadium(IV)-AMP complex occurred in two steps.The first degradation step occurred at 27-392 • C, DTG max = 254 • C, and DTA = 74 and 265 • C (exo), which corresponded to the loss of C 4 H 6 N 2 O 2 (organic moiety), reflected by an observed 25.62% reduction in mass (calculated = 25.44%).The second step occurred between 393 and 714 • C, DTG max = 635 • C, and DTA = 517 • C (endo) due to the loss of C 6 H 10 N 3 O 6 P and the mass associated with this organic moiety (observed = 55.49%,calculated = 56.02%).VO 2 oxide was the final residue at 800 • C.

Figure 7 .
Figure 7. Histology of the pancreas.Pancreatic tissue was collected from each animal after 30 days of treatment.The tissue was sectioned, stained using H & E, and imaged using standard light microscopy at 400× magnification.Double-sided arrows (↕) denote islets of Langerhans.(A) Pancreas from healthy control animal (Group I); (B) Pancreas from STZ-treated diabetic animal (Group II); (C) Pancreas from STZ-treated diabetic animal (Group II); (D) Pancreas from animal treated with oxidovanadium(IV) sulfate alone (Group III); (E) Pancreas from animal treated with oxidovanadium(IV) sulfate alone (Group III); (F) Pancreas from animal treated with oxidovanadium(IV)-AMP complex (Group III).

Figure 7 .
Figure 7. Histology of the pancreas.Pancreatic tissue was collected from each animal after 30 days of treatment.The tissue was sectioned, stained using H & E, and imaged using standard light microscopy at 400× magnification.Double-sided arrows ( ) denote islets of Langerhans.(A) Pancreas from healthy control animal (Group I); (B) Pancreas from STZ-treated diabetic animal (Group II); (C) Pancreas from STZ-treated diabetic animal (Group II); (D) Pancreas from animal treated with oxidovanadium(IV) sulfate alone (Group III); (E) Pancreas from animal treated with oxidovanadium(IV) sulfate alone (Group III); (F) Pancreas from animal treated with oxidovanadium(IV)-AMP complex (Group III).

Figure 8 .
Figure 8. Histology of the liver.Liver tissue was collected from each animal after 30 days of treatment.The tissue was sectioned, stained using H & E, and imaged using standard light microscopy at 400× magnifications.Double-sided arrow ( ) denotes the central vein and single-sided arrows (↑) indicate aggregates of inflammatory cells.(a) Liver from healthy control animal (Group I); (b) Liver from STZ-treated diabetic animal (Group II); (c) Liver from animal treated with oxidovanadium(IV) sulfate alone (Group III); (d) Liver from animal treated with the oxidovanadium(IV)-AMP complex (Group IV).

Table 2 .
Kinetic and thermodynamic parameters of the second thermal decomposition step of the oxidovanadium(IV)-AMP complex.

Table 2 .
Kinetic and thermodynamic parameters of the second thermal decomposition step of the oxidovanadium(IV)-AMP complex.