Limits...
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 liver stained with H & E. Normal architecture of liver tissue after stained with H & E. The hepatocytes are well delineated with centrally located nucleus, seen in control and the four treated groups. This hepatic histology was taken at ×10 magnification from the rats 4 weeks post treatment with ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). The doses were given via oral route repeatedly over the 28 days study period. Portal triad (PT), central vein (CV), hepatocytes (H) and sinusoid (S). The hepatic lobular array is shown to be well maintained with central vein at the centre surrounded by many portal triads.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4048622&req=5

Figure 3: Microscopic appearance of the liver stained with H & E. Normal architecture of liver tissue after stained with H & E. The hepatocytes are well delineated with centrally located nucleus, seen in control and the four treated groups. This hepatic histology was taken at ×10 magnification from the rats 4 weeks post treatment with ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). The doses were given via oral route repeatedly over the 28 days study period. Portal triad (PT), central vein (CV), hepatocytes (H) and sinusoid (S). The hepatic lobular array is shown to be well maintained with central vein at the centre surrounded by many portal triads.

Mentions: Liver histology of the control group showed well-preserved hepatocytes morphology; a well-maintained lobular array with central vein, radiating sinusoids and portal triads were all clearly observed (Figure 3E). The same findings were demonstrated in the treated group from all doses used (Figure 3A,B,C,D). In the case of mild or early liver insult, transferases and or phosphatase levels would be elevated without any clinical symptoms [26]. This may be followed by jaundice, encephalopathy, coagulopathy and possibly some microscopic changes on histology [26]. Here, only slight liver enzymes' derangement was noted at higher doses of ZAL and ZA, and neither clinical nor microscopic evidences of liver toxicity followed.


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 liver stained with H & E. Normal architecture of liver tissue after stained with H & E. The hepatocytes are well delineated with centrally located nucleus, seen in control and the four treated groups. This hepatic histology was taken at ×10 magnification from the rats 4 weeks post treatment with ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). The doses were given via oral route repeatedly over the 28 days study period. Portal triad (PT), central vein (CV), hepatocytes (H) and sinusoid (S). The hepatic lobular array is shown to be well maintained with central vein at the centre surrounded by many portal triads.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Microscopic appearance of the liver stained with H & E. Normal architecture of liver tissue after stained with H & E. The hepatocytes are well delineated with centrally located nucleus, seen in control and the four treated groups. This hepatic histology was taken at ×10 magnification from the rats 4 weeks post treatment with ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). The doses were given via oral route repeatedly over the 28 days study period. Portal triad (PT), central vein (CV), hepatocytes (H) and sinusoid (S). The hepatic lobular array is shown to be well maintained with central vein at the centre surrounded by many portal triads.
Mentions: Liver histology of the control group showed well-preserved hepatocytes morphology; a well-maintained lobular array with central vein, radiating sinusoids and portal triads were all clearly observed (Figure 3E). The same findings were demonstrated in the treated group from all doses used (Figure 3A,B,C,D). In the case of mild or early liver insult, transferases and or phosphatase levels would be elevated without any clinical symptoms [26]. This may be followed by jaundice, encephalopathy, coagulopathy and possibly some microscopic changes on histology [26]. Here, only slight liver enzymes' derangement was noted at higher doses of ZAL and ZA, and neither clinical nor microscopic evidences of liver toxicity followed.

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