Sanil Singh - Academia.edu (original) (raw)
Papers by Sanil Singh
Environmental science and pollution research international, Jan 31, 2017
We studied the possible metal offloading onto the progeny of three pregnant female ragged-tooth s... more We studied the possible metal offloading onto the progeny of three pregnant female ragged-tooth sharks (Carcharias taurus) (C. taurus). The presences of five metals, i.e. aluminium (Al), arsenic (As), cadmium (Cd), lead (Pb) and selenium (Se) were validated by mass spectrometry in the maternal plasma as well as the intracapsular and uterine fluids (UF) in which embryos develop. Metals were ranked in a decreasing concentration as follows: Plasma: As > Al > Se > Pb > Cd; ICF: As > Se > Al > Cd > Pb and UF: As > Se > Al > Cd > Pb. As was present in the highest concentration in all three sharks. Al, Pb and Cd were found to be the highest within the plasma, while concentrations of Se were similar in all three fluids. These results indicate that C. taurus embryos are exposed to metals during early development, but the impact of this exposure remains unknown. To the best of our knowledge, this is the first investigation to confirm the presence of metals ...
Xenobiotica; the fate of foreign compounds in biological systems, 2015
1. The penetration of tetracyclines into the brain has been widely documented. The aim of this wo... more 1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain. 2. The time-dependent distribution was investigated after an i.p. dose of 25 mg/kg at 0, 5, 30, 120, 240, 360 and 480 min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte. 3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (Cmax) of 1034.9 ng/mL at 240 min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5 min and its slow elimination after 360-min p...
Drug testing and analysis, Jan 18, 2015
Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic ... more Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic microbes associated with respiratory and meningeal infections. The potential toxicity of this class of chemical agents is a source of major concern and is becoming a global issue. The aim of this study was to develop a method for the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-Dawley rats, via Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a sensitive LC-MS/MS method to quantify gatifloxacin in plasma, lung, and brain homogenates. A pharmacokinetic profile was observed where there is a double peak pattern; a sharp initial increase in the concentration soon after dosing followed by a steady decline until another increase in concentration after a longer period post dosing in all three biological samples was observe...
ASSAY and Drug Development Technologies, 2015
Rifampicin (RIF) is a major component for short-course chemotherapy against tuberculosis, since i... more Rifampicin (RIF) is a major component for short-course chemotherapy against tuberculosis, since it is active against rapidly metabolizing as well as dormant bacteria. According to the Lipinski rules, RIF should not enter the blood-brain barrier. Visualization of tissue drug distribution is of major importance in pharmacological studies; thus, far imaging of RIF in the brain has been limited to positron emission tomography. We propose using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques as a suitable alternative for the visualization and localization of drug tissue distribution. Using the liquid chromatography mass spectrometric (LCMS) technique, we were able to quantify the concentrations of RIF in the uninfected rat brain; we paired this with matrix-assisted laser desorption/ ionization mass spectrometry imaging (MALDI MSI) to show the time-dependent manner in which RIF is able to enter the brain. Our results show that even at the minute concentrations measured with LCMS/MS we were able visualize the drug and show its exact distribution in the rat brain. Other available methods require nuclear labeling and the detection of gamma rays produced by labeled compounds to visualize the compound and its localization; MALDI MSI is a more recently developed technique, which can provide detailed information on drug distribution in tissues when compared to other imaging techniques. This study shows that without any requirement for complex preprocessing we are able to produce images with a relatively improved resolution and localization than those acquired using more complex imaging methods, showing MALDI MSI to be an invaluable tool in drug distribution studies.
International Journal of Pharmaceutics
ACS Omega
Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths... more Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths can be prevented through the timely administration of naloxone (NLX), a nonselective mu (μ)-, kappa (κ)-, and delta (δ)-opioid receptor antagonist. NLX competitively inhibits opioid-overdose-induced respiratory depression without eliciting any narcotic effect itself. The aim of this study was to investigate the antagonistic action of NLX by comparing its distribution to that of 6-monacetylmorphine (6-MAM), heroin's major metabolite, in a rodent model using mass spectrometric imaging (MSI) in combination with liquid chromatography−tandem mass spectrometry (LC−MS/MS). Male Sprague−Dawley rats (n = 5) received heroin (10 mg kg −1) intraperitoneally, NLX (10 mg kg −1) intranasally, and NLX injected intranasally 5 min after heroin administration. The animals were sacrificed 15 min after dose and brain tissues were harvested. The MSI image analysis showed a region-specific distribution of 6-MAM in the brain regions including the corpus callosum, hippocampal formation, cerebral cortex, corticospinal tracts, caudate putamen, thalamus, globus pallidus, hypothalamus, and basal forebrain regions of the brain. The antagonist had a similar biodistribution throughout the brain in both groups of animals that received NLX or NLX after heroin administration. The MSI analysis demonstrated that the intensity of 6-MAM in these brain regions was reduced following NLX treatment. The decrease in 6-MAM intensity was caused by its displacement by the antagonist and its binding to these receptors in these specific brain regions, consequently enhancing the opioid elimination. These findings will contribute to the evaluation of other narcotic antagonists that might be considered for use in the treatment of drug overdose via MSI.
Food and Chemical Toxicology
European Journal of Pharmacology
ACS Omega
HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurolog... more HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurological disorders (HAND), even with chronic antiretroviral therapy. In order for antiretroviral therapy to be effective in protecting the CNS, these drugs should have the ability to localize in brain areas known to be affected by HIV. Consequently, this study aimed to investigate the localization patterns of three first-line antiretroviral drugs, namely, efavirenz, tenofovir, and emtricitabine, in the rat brain. Liquid chromatography−tandem mass spectrometry (LC−MS/MS) and matrixassisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) were utilized to assess the pharmacokinetics and brain spatial distribution of the three drugs. Each drug was administered (50 mg/kg) to healthy female Sprague−Dawley rats via intraperitoneal administration. LC−MS/MS results showed that all three drugs could be delivered into the brain, although they varied in blood−brain barrier permeability. MALDI-MSI showed a high degree of efavirenz localization across the entire brain, while tenofovir localized mainly in the cortex. Emtricitabine distributed heterogeneously mainly in the thalamus, corpus callosum, and hypothalamus. This study showed that efavirenz, tenofovir, and emtricitabine might be a potential drug combination antiretroviral therapy for CNS protection against HAND.
Journal of Molecular Histology
ASSAY and Drug Development Technologies
Journal of the South African Veterinary Association
Dry pelleted dog food in the South African market is available via supermarkets, pet stores (stan... more Dry pelleted dog food in the South African market is available via supermarkets, pet stores (standard brands [SBs]) and veterinary channels (premium brands [PBs]). For the purpose of this study, the supermarket channel included the cheaper quality foods and PBs were sold via the veterinary channel (n = 20). These feeds were analysed for four main mycotoxins (aflatoxins [AF], fumonisin [FB], ochratoxin A [OTA] and zearalenone [ZEA]) using standard welldescribed extraction, characterisation and quantitation processes. Irrespective of the brand or marketing channel, all foods were contaminated with fungi (mainly Aspergillus flavus, Aspergillus fumigatus and Aspergillus parasiticus) and mycotoxins (most prevalent being aflatoxins and fumonisins). This was observed in all 20 samples irrespective of the marketing channel or perceived quality. Also, many samples within each marketing channel failed the 10 ppb limit for aflatoxin set by regulations in South Africa. Although fumonisin was de...
Food and Chemical Toxicology
Journal of Drug Delivery Science and Technology
Chemistry and Physics of Lipids
Indian Journal of Animal Research
The discovery of the only human pigment bilirubin in the arils of Strelitzia nicolai, has opened ... more The discovery of the only human pigment bilirubin in the arils of Strelitzia nicolai, has opened up a new avenue in medical sciences. Previously, bilirubin was regarded as a toxic compound. Conversely, current case studies show somewhat pre-eminent levels of bilirubin in the body can act as a powerful antioxidant. This study attempted to provide a basis for identifying potential acute toxicities related to arils that comprise bilirubin. Twelve Sprague Dawley rats were divided into four groups. Group A was the control and was administered 1% Tween 20. The other groups were orally dosed with the seed aril extract (250ìg/ml/kgbwt) once a day. After 24 hours, 48 hours and 72 hours one experimental group and the control were sacrificed. Haematological and histological studies indicated a possibility of kidney damage. However, the possibility of the extract causing this damage can be ruled out because this trend was seen in the control groups as well. This study reveals that an acute tria...
International Journal of Pharmaceutics
Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vanco... more Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vancomycin.
Environmental science and pollution research international, Jan 31, 2017
We studied the possible metal offloading onto the progeny of three pregnant female ragged-tooth s... more We studied the possible metal offloading onto the progeny of three pregnant female ragged-tooth sharks (Carcharias taurus) (C. taurus). The presences of five metals, i.e. aluminium (Al), arsenic (As), cadmium (Cd), lead (Pb) and selenium (Se) were validated by mass spectrometry in the maternal plasma as well as the intracapsular and uterine fluids (UF) in which embryos develop. Metals were ranked in a decreasing concentration as follows: Plasma: As > Al > Se > Pb > Cd; ICF: As > Se > Al > Cd > Pb and UF: As > Se > Al > Cd > Pb. As was present in the highest concentration in all three sharks. Al, Pb and Cd were found to be the highest within the plasma, while concentrations of Se were similar in all three fluids. These results indicate that C. taurus embryos are exposed to metals during early development, but the impact of this exposure remains unknown. To the best of our knowledge, this is the first investigation to confirm the presence of metals ...
Xenobiotica; the fate of foreign compounds in biological systems, 2015
1. The penetration of tetracyclines into the brain has been widely documented. The aim of this wo... more 1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain. 2. The time-dependent distribution was investigated after an i.p. dose of 25 mg/kg at 0, 5, 30, 120, 240, 360 and 480 min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte. 3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (Cmax) of 1034.9 ng/mL at 240 min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5 min and its slow elimination after 360-min p...
Drug testing and analysis, Jan 18, 2015
Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic ... more Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic microbes associated with respiratory and meningeal infections. The potential toxicity of this class of chemical agents is a source of major concern and is becoming a global issue. The aim of this study was to develop a method for the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-Dawley rats, via Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a sensitive LC-MS/MS method to quantify gatifloxacin in plasma, lung, and brain homogenates. A pharmacokinetic profile was observed where there is a double peak pattern; a sharp initial increase in the concentration soon after dosing followed by a steady decline until another increase in concentration after a longer period post dosing in all three biological samples was observe...
ASSAY and Drug Development Technologies, 2015
Rifampicin (RIF) is a major component for short-course chemotherapy against tuberculosis, since i... more Rifampicin (RIF) is a major component for short-course chemotherapy against tuberculosis, since it is active against rapidly metabolizing as well as dormant bacteria. According to the Lipinski rules, RIF should not enter the blood-brain barrier. Visualization of tissue drug distribution is of major importance in pharmacological studies; thus, far imaging of RIF in the brain has been limited to positron emission tomography. We propose using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques as a suitable alternative for the visualization and localization of drug tissue distribution. Using the liquid chromatography mass spectrometric (LCMS) technique, we were able to quantify the concentrations of RIF in the uninfected rat brain; we paired this with matrix-assisted laser desorption/ ionization mass spectrometry imaging (MALDI MSI) to show the time-dependent manner in which RIF is able to enter the brain. Our results show that even at the minute concentrations measured with LCMS/MS we were able visualize the drug and show its exact distribution in the rat brain. Other available methods require nuclear labeling and the detection of gamma rays produced by labeled compounds to visualize the compound and its localization; MALDI MSI is a more recently developed technique, which can provide detailed information on drug distribution in tissues when compared to other imaging techniques. This study shows that without any requirement for complex preprocessing we are able to produce images with a relatively improved resolution and localization than those acquired using more complex imaging methods, showing MALDI MSI to be an invaluable tool in drug distribution studies.
International Journal of Pharmaceutics
ACS Omega
Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths... more Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths can be prevented through the timely administration of naloxone (NLX), a nonselective mu (μ)-, kappa (κ)-, and delta (δ)-opioid receptor antagonist. NLX competitively inhibits opioid-overdose-induced respiratory depression without eliciting any narcotic effect itself. The aim of this study was to investigate the antagonistic action of NLX by comparing its distribution to that of 6-monacetylmorphine (6-MAM), heroin's major metabolite, in a rodent model using mass spectrometric imaging (MSI) in combination with liquid chromatography−tandem mass spectrometry (LC−MS/MS). Male Sprague−Dawley rats (n = 5) received heroin (10 mg kg −1) intraperitoneally, NLX (10 mg kg −1) intranasally, and NLX injected intranasally 5 min after heroin administration. The animals were sacrificed 15 min after dose and brain tissues were harvested. The MSI image analysis showed a region-specific distribution of 6-MAM in the brain regions including the corpus callosum, hippocampal formation, cerebral cortex, corticospinal tracts, caudate putamen, thalamus, globus pallidus, hypothalamus, and basal forebrain regions of the brain. The antagonist had a similar biodistribution throughout the brain in both groups of animals that received NLX or NLX after heroin administration. The MSI analysis demonstrated that the intensity of 6-MAM in these brain regions was reduced following NLX treatment. The decrease in 6-MAM intensity was caused by its displacement by the antagonist and its binding to these receptors in these specific brain regions, consequently enhancing the opioid elimination. These findings will contribute to the evaluation of other narcotic antagonists that might be considered for use in the treatment of drug overdose via MSI.
Food and Chemical Toxicology
European Journal of Pharmacology
ACS Omega
HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurolog... more HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurological disorders (HAND), even with chronic antiretroviral therapy. In order for antiretroviral therapy to be effective in protecting the CNS, these drugs should have the ability to localize in brain areas known to be affected by HIV. Consequently, this study aimed to investigate the localization patterns of three first-line antiretroviral drugs, namely, efavirenz, tenofovir, and emtricitabine, in the rat brain. Liquid chromatography−tandem mass spectrometry (LC−MS/MS) and matrixassisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) were utilized to assess the pharmacokinetics and brain spatial distribution of the three drugs. Each drug was administered (50 mg/kg) to healthy female Sprague−Dawley rats via intraperitoneal administration. LC−MS/MS results showed that all three drugs could be delivered into the brain, although they varied in blood−brain barrier permeability. MALDI-MSI showed a high degree of efavirenz localization across the entire brain, while tenofovir localized mainly in the cortex. Emtricitabine distributed heterogeneously mainly in the thalamus, corpus callosum, and hypothalamus. This study showed that efavirenz, tenofovir, and emtricitabine might be a potential drug combination antiretroviral therapy for CNS protection against HAND.
Journal of Molecular Histology
ASSAY and Drug Development Technologies
Journal of the South African Veterinary Association
Dry pelleted dog food in the South African market is available via supermarkets, pet stores (stan... more Dry pelleted dog food in the South African market is available via supermarkets, pet stores (standard brands [SBs]) and veterinary channels (premium brands [PBs]). For the purpose of this study, the supermarket channel included the cheaper quality foods and PBs were sold via the veterinary channel (n = 20). These feeds were analysed for four main mycotoxins (aflatoxins [AF], fumonisin [FB], ochratoxin A [OTA] and zearalenone [ZEA]) using standard welldescribed extraction, characterisation and quantitation processes. Irrespective of the brand or marketing channel, all foods were contaminated with fungi (mainly Aspergillus flavus, Aspergillus fumigatus and Aspergillus parasiticus) and mycotoxins (most prevalent being aflatoxins and fumonisins). This was observed in all 20 samples irrespective of the marketing channel or perceived quality. Also, many samples within each marketing channel failed the 10 ppb limit for aflatoxin set by regulations in South Africa. Although fumonisin was de...
Food and Chemical Toxicology
Journal of Drug Delivery Science and Technology
Chemistry and Physics of Lipids
Indian Journal of Animal Research
The discovery of the only human pigment bilirubin in the arils of Strelitzia nicolai, has opened ... more The discovery of the only human pigment bilirubin in the arils of Strelitzia nicolai, has opened up a new avenue in medical sciences. Previously, bilirubin was regarded as a toxic compound. Conversely, current case studies show somewhat pre-eminent levels of bilirubin in the body can act as a powerful antioxidant. This study attempted to provide a basis for identifying potential acute toxicities related to arils that comprise bilirubin. Twelve Sprague Dawley rats were divided into four groups. Group A was the control and was administered 1% Tween 20. The other groups were orally dosed with the seed aril extract (250ìg/ml/kgbwt) once a day. After 24 hours, 48 hours and 72 hours one experimental group and the control were sacrificed. Haematological and histological studies indicated a possibility of kidney damage. However, the possibility of the extract causing this damage can be ruled out because this trend was seen in the control groups as well. This study reveals that an acute tria...
International Journal of Pharmaceutics
Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vanco... more Synthesis of an oleic acid based pH-responsive lipid and its application in nanodelivery of vancomycin.