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Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study.

Kura AU, Cheah PS, Hussein MZ, Hassan Z, Tengku Azmi TI, Hussein NF, Fakurazi S - Nanoscale Res Lett (2014)

Bottom Line: Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05).However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07).The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Vaccine and Immunotherapeutic, Institute of Bioscience, Universiti Putra Malaysia, Selangor 43400, Malaysia.

ABSTRACT
Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

No MeSH data available.


Related in: MedlinePlus

Micrograms showing neuronal nucleus from the substantia nigra. TEM ultra-structural micrographs of the rat substantia nigra (n = 3) showing the nucleus of a neuron after treatment with (A) ZALH, (B) ZALL, (C) ZAH, (D) ZAL and (E) VC. Arrow pointing to the intact round-shaped nuclei with a densely peripheral nuclear chromatin condensation (opaque nuclei membrane) and mitochondria (M), with well-outlined cristae and intact opaque membrane in the control group. Similar nucleic and mitochondrial structure and shape were found in the entire treated groups at ×10,000 magnification.
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Figure 9: Micrograms showing neuronal nucleus from the substantia nigra. TEM ultra-structural micrographs of the rat substantia nigra (n = 3) showing the nucleus of a neuron after treatment with (A) ZALH, (B) ZALL, (C) ZAH, (D) ZAL and (E) VC. Arrow pointing to the intact round-shaped nuclei with a densely peripheral nuclear chromatin condensation (opaque nuclei membrane) and mitochondria (M), with well-outlined cristae and intact opaque membrane in the control group. Similar nucleic and mitochondrial structure and shape were found in the entire treated groups at ×10,000 magnification.

Mentions: The TEM analysis of the neuronal cells from substantia nigra demonstrated an intact neuron with well-defined nucleus that has a well-delineated peripheral nuclear condensation, which is densely opaque (Figure 9). The shapes were found to be round to ovoid with abundant other cellular organelles notably the mitochondria maintaining its cristae and opaque membrane. In brief, ultra-structural manifestations of the neurons from the substantia nigra were comparatively the same in the control and the nanocomposite-treated groups (Figure 9).


Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study.

Kura AU, Cheah PS, Hussein MZ, Hassan Z, Tengku Azmi TI, Hussein NF, Fakurazi S - Nanoscale Res Lett (2014)

Micrograms showing neuronal nucleus from the substantia nigra. TEM ultra-structural micrographs of the rat substantia nigra (n = 3) showing the nucleus of a neuron after treatment with (A) ZALH, (B) ZALL, (C) ZAH, (D) ZAL and (E) VC. Arrow pointing to the intact round-shaped nuclei with a densely peripheral nuclear chromatin condensation (opaque nuclei membrane) and mitochondria (M), with well-outlined cristae and intact opaque membrane in the control group. Similar nucleic and mitochondrial structure and shape were found in the entire treated groups at ×10,000 magnification.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048622&req=5

Figure 9: Micrograms showing neuronal nucleus from the substantia nigra. TEM ultra-structural micrographs of the rat substantia nigra (n = 3) showing the nucleus of a neuron after treatment with (A) ZALH, (B) ZALL, (C) ZAH, (D) ZAL and (E) VC. Arrow pointing to the intact round-shaped nuclei with a densely peripheral nuclear chromatin condensation (opaque nuclei membrane) and mitochondria (M), with well-outlined cristae and intact opaque membrane in the control group. Similar nucleic and mitochondrial structure and shape were found in the entire treated groups at ×10,000 magnification.
Mentions: The TEM analysis of the neuronal cells from substantia nigra demonstrated an intact neuron with well-defined nucleus that has a well-delineated peripheral nuclear condensation, which is densely opaque (Figure 9). The shapes were found to be round to ovoid with abundant other cellular organelles notably the mitochondria maintaining its cristae and opaque membrane. In brief, ultra-structural manifestations of the neurons from the substantia nigra were comparatively the same in the control and the nanocomposite-treated groups (Figure 9).

Bottom Line: Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05).However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07).The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Vaccine and Immunotherapeutic, Institute of Bioscience, Universiti Putra Malaysia, Selangor 43400, Malaysia.

ABSTRACT
Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

No MeSH data available.


Related in: MedlinePlus