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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

Average weight gain with time. The bar chart showed average weight of rats per group at days 0, 7, 14 and 21 of sub-acute toxicity study. There is an obvious increase in the animal's weight; it is shown to be continuous in the four treatment groups as well as the vehicle control. Zinc-aluminium levodopa nanocomposite high dose (ZALH 500 mg/kg), zinc-aluminium levodopa nanocomposite low dose (ZALL 5 mg/kg), zinc-aluminium nanocomposite high dose (ZAH 500 mg/kg), zinc-aluminium nanocomposite low dose (ZAL 5 mg/kg), vehicle control (VC normal saline 100 ml/kg body weight). There is statistically significant difference (#) between day 0 and all other days in all the groups (p < 0.05). One-way ANOVA was used, and data are expressed as means ± SD.
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Figure 1: Average weight gain with time. The bar chart showed average weight of rats per group at days 0, 7, 14 and 21 of sub-acute toxicity study. There is an obvious increase in the animal's weight; it is shown to be continuous in the four treatment groups as well as the vehicle control. Zinc-aluminium levodopa nanocomposite high dose (ZALH 500 mg/kg), zinc-aluminium levodopa nanocomposite low dose (ZALL 5 mg/kg), zinc-aluminium nanocomposite high dose (ZAH 500 mg/kg), zinc-aluminium nanocomposite low dose (ZAL 5 mg/kg), vehicle control (VC normal saline 100 ml/kg body weight). There is statistically significant difference (#) between day 0 and all other days in all the groups (p < 0.05). One-way ANOVA was used, and data are expressed as means ± SD.

Mentions: The animals treated with zinc-aluminium layered hydroxide nanocomposite intercalated and unintercalated with levodopa over 28 days showed no mortality. The food and water intake in both control and treatment groups were unaffected during the study period. No signs of toxicity, such as vomiting, diarrhoea, paralysis, convulsion, restless, irritation, bleeding and breathing difficulties were observed in any of the groups (Table 2). During the course of experiment, rats treated with high and low doses of nanocomposite showed a sustained weight gain similar to their counterpart in the vehicle control group. The weight gain was shown to be continuous over the study period; statistically, the difference in weight gain between day 0 and all other days in all the groups is significant (p < 0.05) (Figure 1). However, body weight changes between weeks were found to be statistically significant (p < 0.05), meaning the weight gain in all group from day zero (0) is statistically significant compared to weight in the subsequent weeks. The coefficient of the brain, liver, spleen, heart and kidney was presented in Table 3. It is the ratio of these organs to the whole body taken on the 28th day. There were no significant differences observed in the coefficients of these organs. Thus, 28 days of repeated doses of ZAL and ZA at 5 and 500 mg/kg, via oral route did not show any effect on these organs' weight in relation to the whole body weight. This implies that orally administered ZAL and ZA at 5 or 500 mg/kg respectively do not induce any obvious clinical toxicity or do they resulted in any animal demise.


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)

Average weight gain with time. The bar chart showed average weight of rats per group at days 0, 7, 14 and 21 of sub-acute toxicity study. There is an obvious increase in the animal's weight; it is shown to be continuous in the four treatment groups as well as the vehicle control. Zinc-aluminium levodopa nanocomposite high dose (ZALH 500 mg/kg), zinc-aluminium levodopa nanocomposite low dose (ZALL 5 mg/kg), zinc-aluminium nanocomposite high dose (ZAH 500 mg/kg), zinc-aluminium nanocomposite low dose (ZAL 5 mg/kg), vehicle control (VC normal saline 100 ml/kg body weight). There is statistically significant difference (#) between day 0 and all other days in all the groups (p < 0.05). One-way ANOVA was used, and data are expressed as means ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Average weight gain with time. The bar chart showed average weight of rats per group at days 0, 7, 14 and 21 of sub-acute toxicity study. There is an obvious increase in the animal's weight; it is shown to be continuous in the four treatment groups as well as the vehicle control. Zinc-aluminium levodopa nanocomposite high dose (ZALH 500 mg/kg), zinc-aluminium levodopa nanocomposite low dose (ZALL 5 mg/kg), zinc-aluminium nanocomposite high dose (ZAH 500 mg/kg), zinc-aluminium nanocomposite low dose (ZAL 5 mg/kg), vehicle control (VC normal saline 100 ml/kg body weight). There is statistically significant difference (#) between day 0 and all other days in all the groups (p < 0.05). One-way ANOVA was used, and data are expressed as means ± SD.
Mentions: The animals treated with zinc-aluminium layered hydroxide nanocomposite intercalated and unintercalated with levodopa over 28 days showed no mortality. The food and water intake in both control and treatment groups were unaffected during the study period. No signs of toxicity, such as vomiting, diarrhoea, paralysis, convulsion, restless, irritation, bleeding and breathing difficulties were observed in any of the groups (Table 2). During the course of experiment, rats treated with high and low doses of nanocomposite showed a sustained weight gain similar to their counterpart in the vehicle control group. The weight gain was shown to be continuous over the study period; statistically, the difference in weight gain between day 0 and all other days in all the groups is significant (p < 0.05) (Figure 1). However, body weight changes between weeks were found to be statistically significant (p < 0.05), meaning the weight gain in all group from day zero (0) is statistically significant compared to weight in the subsequent weeks. The coefficient of the brain, liver, spleen, heart and kidney was presented in Table 3. It is the ratio of these organs to the whole body taken on the 28th day. There were no significant differences observed in the coefficients of these organs. Thus, 28 days of repeated doses of ZAL and ZA at 5 and 500 mg/kg, via oral route did not show any effect on these organs' weight in relation to the whole body weight. This implies that orally administered ZAL and ZA at 5 or 500 mg/kg respectively do not induce any obvious clinical toxicity or do they resulted in any animal demise.

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