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  1. Nurhidanatasha Abu Bakar, Zainal Abidin Abu Hasan, Nurul Izza Nordin, Bohari Mohamad Yamin
    Sains Malaysiana, 2007;36:39-44.
    Ferrocene plays an important role in chemistry and industry. The structure and bonding discovered in ferrocene has led to new developments in organometallic chemistry, and the discovery of entirely new organometallic compounds. The high stability of this compound is also related to its interesting electrochemical properties that makes it effective electrochemical, reduction and combustion catalysts. Nevertheless, ferrocenyl derivatives are also capable of enhancing the activity of certain biological compounds. Indeed, recently ferrocene and its derivatives have been incorporated into antimalarial agents. Therefore, the evaluation of the possible toxic effects of ferrocene derivative called ferrocenium tetrachloroantimonate (C10H10FeSbCl4 or FC) on acute and subchronic toxicity tests using different dose concentrations according to the body weight for different time interval was carried out in an in vivo model. Results showed that FC was acutely toxic with the LD50 value of 194.70 mg/kg body weight (BW) with signs of toxicity associated with respiratory depression. In the 28-day acute toxicity test, the dose of 100 mg/kg BW resulted in 60 % mortality with signs of gross toxicity, adverse pharmacological effects or abnormal behaviors during the 28 days observation. While in the 90-day subchronic toxicity test at the lower dose of 10 mg/kg BW, however, showed no significant differences (p>0.05) in the mortality rates, and showed no sign of toxicity. These results indicated that FC had different toxicity levels, and mice appeared to tolerate well at the lower dose of 10 mg/kg BW.
    Matched MeSH terms: Toxicity Tests, Subchronic
  2. Christapher PV, Parasuraman S, Asmawi MZ, Murugaiyah V
    Regul Toxicol Pharmacol, 2017 Jun;86:33-41.
    PMID: 28229903 DOI: 10.1016/j.yrtph.2017.02.005
    Medicinal plant preparations may contain high levels of toxic chemical constituents to potentially cause serious harm to animals and/or humans. Thus, toxicity studies are important to assess the toxic effects of plant derived products. Polygonum minus is used traditionally for different ailments in Southeast Asia. This study was conducted to establish the acute and subchronic toxicity profile of the methanol extract of P. minus leaves. The acute toxicity study showed that the methanol extract of P. minus is safe even at the highest dose tested of 2000 mg/kg in female Sprague Dawley rats. There were no behavioural or physiological changes and gross pathological abnormalities observed. The subchronic toxicity study of methanol extract of P. minus at 250, 500, 1000 and 2000 mg/kg were conducted in both sexes of Sprague Dawley rats. There were no changes observed in the extract treated animal's body weight, food and water intake, motor coordination, behaviour and mental alertness. The values of haematological and biochemical parameters were not different between the treated and control animals. The relative organ weights of extract-treated animals did not differ with that of control animals. Based on the present findings, the methanol extract of P. minus leaves could be considered safe up to the dose of 2000 mg/kg.
    Matched MeSH terms: Toxicity Tests, Subchronic*
  3. Manaharan T, Chakravarthi S, Radhakrishnan AK, Palanisamy UD
    Toxicol Rep, 2014;1:718-725.
    PMID: 28962285 DOI: 10.1016/j.toxrep.2014.09.006
    In this study, the acute and subchronic toxicity effect of the Syzygium aqueum leaf extract (SA) was evaluated. For the acute toxicity study, a single dose of 2000 mg/kg of the SA was given by oral-gavage to male Sprague-Dawley (SD) rats. The rats were observed for mortality and toxicity signs for 14 days. In the subchronic toxicity study the SA was administered orally at doses of 50, 100, and 200 mg/kg per day for 28 days to male SD rats. The animals were sacrificed at the end of the experiment. The parameters measured including food and water intake, body weight, absolute and relative organ weight, blood biochemical tests and histopathology observation. In both the acute and subchronic toxicity studies, SA did not show any visible signs of toxicity. There were also no significant differences between the control and SA treated rats in terms of their food and water intake, body weight, absolute and relative organ weight, biochemical parameters or gross and microscopic appearance of the organs. There were no acute or subchronic toxicity observed and our results indicate that this extract could be devoid of any toxic risk. This is the first in vivo study reported the safety and toxicity of SA.
    Matched MeSH terms: Toxicity Tests, Subchronic
  4. Yuet Ping K, Darah I, Chen Y, Sreeramanan S, Sasidharan S
    Biomed Res Int, 2013;2013:182064.
    PMID: 24386634 DOI: 10.1155/2013/182064
    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5,000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5,000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1,000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity.
    Matched MeSH terms: Toxicity Tests, Subchronic*
  5. Lakshmanan H, Raman J, David P, Wong KH, Naidu M, Sabaratnam V
    J Ethnopharmacol, 2016 Dec 24;194:1051-1059.
    PMID: 27816657 DOI: 10.1016/j.jep.2016.10.084
    ETHNOPHARMACOLOGICAL RELEVANCE: Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments.

    AIM OF THE STUDY: The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study.

    MATERIALS AND METHODS: In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes.

    RESULTS: No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen.

    CONCLUSION: The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic.

    Matched MeSH terms: Toxicity Tests, Subchronic/methods
  6. Nasir NLM, Kamsani NE, Mohtarrudin N, Tohid SFM, Zakaria ZA
    Pak J Pharm Sci, 2020 Sep;33(5):2009-2016.
    PMID: 33824108
    Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri" belongs to the family Muntingiaceae and has been scientifically demonstrated to exert various pharmacological activities. The objectives of the current study are to evaluate the antioxidant activities and to determine the subchronic toxicity of 90 days orally-administered methanol extract of M. calabura (MEMC) in male Sprague Dawley rats. The rats were randomly divided into four groups (n=6). Vehicle control received 8% tween 80 and treatment group received 50, 250 and 500 mg/kg of MEMC orally administered daily for 90 days. Blood collection was carried out to obtain the hematological and biochemical profile of the rats. The organs harvested were subjected to histopathological analysis. For the antioxidant test, the extract was subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging activity, total phenolic content (TPC) and phytochemical screening. Results obtained show that no adverse effects were observed during the experimental period. Hematological and biochemical analysis also showed no significant changes in this toxicity study. Besides, antioxidant analyses revealed that MEMC has higher DPPH- and SOD-radical scavenges activity as well as higher TPC value. In conclusion, M. calabura is safe for consumption and possesses beneficial antioxidant effect.
    Matched MeSH terms: Toxicity Tests, Subchronic
  7. Hor SY, Ahmad M, Farsi E, Lim CP, Asmawi MZ, Yam MF
    J Ethnopharmacol, 2011 Oct 11;137(3):1067-76.
    PMID: 21767625 DOI: 10.1016/j.jep.2011.07.007
    Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats.
    Matched MeSH terms: Toxicity Tests, Subchronic*
  8. Hor SY, Ahmad M, Farsi E, Yam MF, Hashim MA, Lim CP, et al.
    Regul Toxicol Pharmacol, 2012 Jun;63(1):106-14.
    PMID: 22440551 DOI: 10.1016/j.yrtph.2012.03.006
    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days.
    Matched MeSH terms: Toxicity Tests, Subchronic
  9. Yeap SK, Yong CY, Faruq U, Ong HK, Amin ZBM, Ho WY, et al.
    BMC Complement Med Ther, 2021 Mar 09;21(1):86.
    PMID: 33750373 DOI: 10.1186/s12906-021-03260-y
    BACKGROUND: Phyllanthus tenellus Roxb. has been traditionally used to treat inflammation and liver diseases and its medicinal property may be due to the presence of relatively high levels of hydrosable tannins. Recent report revealed that pressurized hot water extraction of P. tenellus significantly increased the concentration of hydrolysable tannins and its catabolites. Thus, this study was aimed to evaluate the in vivo toxicity and antioxidant capacity of pressurized hot water extraction of P. tenellus on healthy mice.

    METHODS: Pressurized hot water extraction P. tenellus was carried out and standardized to 7.9% hydrosable tannins. In vitro toxicity of the extract was tested on NIH 3 T3 cell by MTT assay. The cellular antioxidant level was quantified by measuring cellular level of glutathione. Oral sub-chronic toxicity (200, 1000 and 3000 mg/kg body weight) of P. tenellus extract were evaluated on healthy mice. Liver and kidney antioxidant level was quantified by measuring levels of Ferric Reducing Antioxidant Potential (FRAP), superoxide dismutase, glutathione.

    RESULTS: The P. tenellus extract did not induce cytotoxicity on murine NIH 3 T3 cells up to 200 μg/mL for 48 h. Besides, level of glutathione was higher in the extract treated NIH 3 T3 cells. P. tenellus extract did not cause mortality at all tested concentration. When treated with 1000 mg/kg of the extract, serum liver enzymes (ALP and ALT) and LDH were lower than normal control and mice treated with 200 mg/kg of extract. Moreover, SOD, FRAP and glutathione levels of liver of the mice treated with 200 and 1000 mg/kg of extract were higher than the normal control mice. On the other hand, when treated with 3000 mg/kg of extract, serum liver enzymes (ALP and ALT) and LDH were higher than normal mice without changing the liver SOD and glutathione level, which may contribute to the histological sign of ballooning hepatocyte.

    CONCLUSION: P. tenellus extract standardized with 7.9% hydrosable tannins and their catabolites increased the antioxidant levels while reducing the nitric oxide levels in both liver and kidney without causing any acute and sub-chronic toxicity in the mice.

    Matched MeSH terms: Toxicity Tests, Subchronic
  10. Al-Afifi NA, Alabsi AM, Bakri MM, Ramanathan A
    BMC Complement Altern Med, 2018 Feb 05;18(1):50.
    PMID: 29402248 DOI: 10.1186/s12906-018-2110-3
    BACKGROUND: Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations.

    METHODS: In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology.

    RESULTS: In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control.

    CONCLUSION: This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose.

    Matched MeSH terms: Toxicity Tests, Subchronic
  11. Farsi E, Shafaei A, Hor SY, Ahamed MB, Yam MF, Asmawi MZ, et al.
    Clinics (Sao Paulo), 2013 Jun;68(6):865-75.
    PMID: 23778480 DOI: 10.6061/clinics/2013(06)23
    Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves.
    Matched MeSH terms: Toxicity Tests, Subchronic
  12. Sabetghadam A, Ramanathan S, Sasidharan S, Mansor SM
    J Ethnopharmacol, 2013 Apr 19;146(3):815-23.
    PMID: 23422336 DOI: 10.1016/j.jep.2013.02.008
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa is a popular medicinal plant in Southeast Asia which is commonly used for its morphine-like effects. Although the analgesic properties of Mitragyna speciosa and its ability to ameliorate withdrawal signs after abrupt cessation of opioid abuse are well known, information about the long-term safety of the plant's active compounds is lacking. In this work, we evaluated the effects of sub-chronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa leaves in rats.

    MATERIALS AND METHODS: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.

    RESULTS: No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.

    CONCLUSIONS: The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1-10mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.

    Matched MeSH terms: Toxicity Tests, Subchronic
  13. Abdalla YOA, Nyamathulla S, Shamsuddin N, Arshad NM, Mun KS, Awang K, et al.
    Toxicol Appl Pharmacol, 2018 10 01;356:204-213.
    PMID: 30138658 DOI: 10.1016/j.taap.2018.08.014
    1'-S-1'-acetoxychavicol acetate (ACA) has been previously reported to reduce tumor volume in nude mice, at an effective dose of 1.56 mg/kg body weight. However, the detailed toxicological profile for ACA has not yet been performed. Herein, we investigated the toxicity of intravenous administration of ACA in male and female Sprague-Dawley rats, both acutely (with single doses of 2.00, 4.00 and 6.66 mg/kg body weight, for 14 days), and sub-acutely (with weekly injections of 0.66, 1.33, and 2.22 mg/kg, for 28 days). In both toxicity studies, treatment with ACA did not affect behavior, food/water intake or body weight, nor did it induce any changes in clinically relevant hematological and biochemical parameters or mortality, suggesting that the LD50 of ACA was higher than 6.66 mg/kg body weight, regardless of sex. Sub-acutely, there was however, mild focal inflammation of kidneys and lobular hepatitis, but these were not associated with significant functional adverse effects. Therefore, the no-observed-adverse-effect level (NOAEL) for intravenous administration of ACA in the present 28-day sub-acute study was 2.22 mg/kg body weight, in both male and female rats. These findings provide useful information regarding the safety of ACA use in a healthy, non-tumor-bearing rat model.
    Matched MeSH terms: Toxicity Tests, Subchronic
  14. Abu N, Zamberi NR, Yeap SK, Nordin N, Mohamad NE, Romli MF, et al.
    BMC Complement Altern Med, 2018 Jan 27;18(1):31.
    PMID: 29374471 DOI: 10.1186/s12906-018-2102-3
    BACKGROUND: Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated.

    METHODS: In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice.

    RESULTS: Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays.

    CONCLUSION: Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored.

    Matched MeSH terms: Toxicity Tests, Subchronic
  15. Kumar MR, Yeap SK, Mohamad NE, Abdullah JO, Masarudin MJ, Khalid M, et al.
    BMC Complement Med Ther, 2021 Jul 01;21(1):183.
    PMID: 34210310 DOI: 10.1186/s12906-021-03358-3
    BACKGROUND: In recent years, researchers are interested in the discovery of active compounds from traditional remedies and natural sources, as they reveal higher therapeutic efficacies and improved toxicological profiles. Among the various traditional treatments that have been widely studied and explored for their potential therapeutic benefits, kefir, a fermented beverage, demonstrates a broad spectrum of pharmacological properties, including antioxidant, anti-inflammation, and healing activities. These health-promoting properties of kefir vary among the kefir cultures found at the different part of the world as different media and culture conditions are used for kefir maintenance and fermentation.

    METHODS: This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.

    RESULTS: The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir was Lactobacillus hilgardii followed by Lactobacillus harbinensis, Acetobacter lovaniensis, Lactobacillus satsumensis, Acetobacter tropicalis, Lactobacillus zeae, and Oenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.

    CONCLUSIONS: This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.

    Matched MeSH terms: Toxicity Tests, Subchronic
  16. Lakshmanan H, Raman J, Pandian A, Kuppamuthu K, Nanjian R, Sabaratam V, et al.
    Regul Toxicol Pharmacol, 2016 Aug;79:25-34.
    PMID: 27177820 DOI: 10.1016/j.yrtph.2016.05.010
    Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P 
    Matched MeSH terms: Toxicity Tests, Subchronic*
  17. Gorain B, Choudhury H, Tekade RK, Karan S, Jaisankar P, Pal TK
    Regul Toxicol Pharmacol, 2016 Dec;82:20-31.
    PMID: 27815174 DOI: 10.1016/j.yrtph.2016.10.020
    Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients.
    Matched MeSH terms: Toxicity Tests, Subchronic
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