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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

Microscopic appearance of the kidney stained with H & E. Microarchitecture of kidney tissues stained with H & E and viewed at ×10 magnification in rats 4 weeks post-exposure to different concentrations of ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). G, glomerular; T, tubule. Micrographs (A) and (C) (encircled areas) show some leukocyte infiltrations which are eosinophilic glomerular due to inflammation likely caused by high dose of the nanocomposite delivery system. The two areas from (A) and (C) were viewed under higher magnification and they are presented in Figure 7.
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Figure 7: Microscopic appearance of the kidney stained with H & E. Microarchitecture of kidney tissues stained with H & E and viewed at ×10 magnification in rats 4 weeks post-exposure to different concentrations of ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). G, glomerular; T, tubule. Micrographs (A) and (C) (encircled areas) show some leukocyte infiltrations which are eosinophilic glomerular due to inflammation likely caused by high dose of the nanocomposite delivery system. The two areas from (A) and (C) were viewed under higher magnification and they are presented in Figure 7.

Mentions: Some inflammatory changes were noticed in kidney sections of ZALH and ZAH groups compared to VC group (Figures 7A, 4B, and 8). Notably, there were some leukocyte infiltrations in both cases. These changes are dose dependent, seen only in the two high-dose-treated rats but not the lower-dose-exposed animals. Drug-induced renal toxicity in the form of inflammation is a common finding [28], some of which are dose related. They can affect the glomerulus, renal tubular cells and/or the surrounding renal interstitium. This finding is also in agreement with the pathological observation in the case of orally administrated zinc oxide nanoparticle to mice [29], where both oral and intra-peritoneal administration of the nanoparticle at different doses demonstrated inflammatory changes in the liver, kidney and lungs [29].


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)

Microscopic appearance of the kidney stained with H & E. Microarchitecture of kidney tissues stained with H & E and viewed at ×10 magnification in rats 4 weeks post-exposure to different concentrations of ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). G, glomerular; T, tubule. Micrographs (A) and (C) (encircled areas) show some leukocyte infiltrations which are eosinophilic glomerular due to inflammation likely caused by high dose of the nanocomposite delivery system. The two areas from (A) and (C) were viewed under higher magnification and they are presented in Figure 7.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Microscopic appearance of the kidney stained with H & E. Microarchitecture of kidney tissues stained with H & E and viewed at ×10 magnification in rats 4 weeks post-exposure to different concentrations of ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). G, glomerular; T, tubule. Micrographs (A) and (C) (encircled areas) show some leukocyte infiltrations which are eosinophilic glomerular due to inflammation likely caused by high dose of the nanocomposite delivery system. The two areas from (A) and (C) were viewed under higher magnification and they are presented in Figure 7.
Mentions: Some inflammatory changes were noticed in kidney sections of ZALH and ZAH groups compared to VC group (Figures 7A, 4B, and 8). Notably, there were some leukocyte infiltrations in both cases. These changes are dose dependent, seen only in the two high-dose-treated rats but not the lower-dose-exposed animals. Drug-induced renal toxicity in the form of inflammation is a common finding [28], some of which are dose related. They can affect the glomerulus, renal tubular cells and/or the surrounding renal interstitium. This finding is also in agreement with the pathological observation in the case of orally administrated zinc oxide nanoparticle to mice [29], where both oral and intra-peritoneal administration of the nanoparticle at different doses demonstrated inflammatory changes in the liver, kidney and lungs [29].

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