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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

Effect of ZAL and ZA on biochemical parameters of rats after oral treatment. Effect of ZAL and ZA on biochemical parameters of rats after oral treatment for twenty eight days using 5 mg/kg and 500 mg/kg doses. (A) Liver enzymes. (B) Renal function tests. All data are expressed as means ± SD and were compared using one-way ANOVA (n = 5). Differences with p < 0.05 are considered statistically significant. From the table, AST in ZALH, ZAH and ZAL was notably elevated compared to VC, but the difference were not significant (p > 0.05). However, the differences in AST/ALT ratio of ZALH (#) and ZAH (#) were statistically significant compare to VC (#) group. Other parameters measured were found to have no statistical significant difference compared to the control group (p > 0.05). ALT (alanine aminotransferase), AST (aspartate aminotransferase), CK (creatine kinase), Creat (Creatinine), GGT (Gamma-glutamyltransferase), Na (sodium), K (potassium), Cl (chloride).
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Figure 2: Effect of ZAL and ZA on biochemical parameters of rats after oral treatment. Effect of ZAL and ZA on biochemical parameters of rats after oral treatment for twenty eight days using 5 mg/kg and 500 mg/kg doses. (A) Liver enzymes. (B) Renal function tests. All data are expressed as means ± SD and were compared using one-way ANOVA (n = 5). Differences with p < 0.05 are considered statistically significant. From the table, AST in ZALH, ZAH and ZAL was notably elevated compared to VC, but the difference were not significant (p > 0.05). However, the differences in AST/ALT ratio of ZALH (#) and ZAH (#) were statistically significant compare to VC (#) group. Other parameters measured were found to have no statistical significant difference compared to the control group (p > 0.05). ALT (alanine aminotransferase), AST (aspartate aminotransferase), CK (creatine kinase), Creat (Creatinine), GGT (Gamma-glutamyltransferase), Na (sodium), K (potassium), Cl (chloride).

Mentions: Biochemical parameters from serum were measured to check for any liver and or kidney damage, which may be indicative of injury following repeated doses of the nanodelivery systems. An enzyme of liver mitochondrial and cytosol, aspartate aminotransferase (AST) in ZALH, ZAH and ZAL groups was shown to be elevated compared to VC group, but the difference was not significant (p > 0.05) (Figure 2A). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of ZALH and ZAH were statistically significant compare to VC group (p < 0.05). Other biochemical parameters measured from the serum of the treated groups were found to have no statistical significant difference compared to the control group (p > 0.05).


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)

Effect of ZAL and ZA on biochemical parameters of rats after oral treatment. Effect of ZAL and ZA on biochemical parameters of rats after oral treatment for twenty eight days using 5 mg/kg and 500 mg/kg doses. (A) Liver enzymes. (B) Renal function tests. All data are expressed as means ± SD and were compared using one-way ANOVA (n = 5). Differences with p < 0.05 are considered statistically significant. From the table, AST in ZALH, ZAH and ZAL was notably elevated compared to VC, but the difference were not significant (p > 0.05). However, the differences in AST/ALT ratio of ZALH (#) and ZAH (#) were statistically significant compare to VC (#) group. Other parameters measured were found to have no statistical significant difference compared to the control group (p > 0.05). ALT (alanine aminotransferase), AST (aspartate aminotransferase), CK (creatine kinase), Creat (Creatinine), GGT (Gamma-glutamyltransferase), Na (sodium), K (potassium), Cl (chloride).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of ZAL and ZA on biochemical parameters of rats after oral treatment. Effect of ZAL and ZA on biochemical parameters of rats after oral treatment for twenty eight days using 5 mg/kg and 500 mg/kg doses. (A) Liver enzymes. (B) Renal function tests. All data are expressed as means ± SD and were compared using one-way ANOVA (n = 5). Differences with p < 0.05 are considered statistically significant. From the table, AST in ZALH, ZAH and ZAL was notably elevated compared to VC, but the difference were not significant (p > 0.05). However, the differences in AST/ALT ratio of ZALH (#) and ZAH (#) were statistically significant compare to VC (#) group. Other parameters measured were found to have no statistical significant difference compared to the control group (p > 0.05). ALT (alanine aminotransferase), AST (aspartate aminotransferase), CK (creatine kinase), Creat (Creatinine), GGT (Gamma-glutamyltransferase), Na (sodium), K (potassium), Cl (chloride).
Mentions: Biochemical parameters from serum were measured to check for any liver and or kidney damage, which may be indicative of injury following repeated doses of the nanodelivery systems. An enzyme of liver mitochondrial and cytosol, aspartate aminotransferase (AST) in ZALH, ZAH and ZAL groups was shown to be elevated compared to VC group, but the difference was not significant (p > 0.05) (Figure 2A). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of ZALH and ZAH were statistically significant compare to VC group (p < 0.05). Other biochemical parameters measured from the serum of the treated groups were found to have no statistical significant difference compared to the control group (p > 0.05).

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