Glucosamine Enhances Paracetamol Bioavailability by Reducing Its Metabolism

Qinna, Nidal A.; Shubbar, Maryam H.; Matalka, Khalid Z.; Al-Jbour, Nawzat; Ghattas, Mohammad A.; Badwan, Adnan A.

doi:10.1002/jps.24269

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…An oral dose of 2,800 mg/kg/d of APAP was used to induce hepatotoxicity in rats. 9 APAP stock was freshly prepared before use by weighing appropriate amount of the drug and suspending it in distilled water for in vivo testing or in RPMI media for in vitro intoxications of isolated hepatocytes with a concentration of 10 mM APAP. 24 …”

Section: Methodsmentioning

confidence: 99%

“…Groups VI and VII were treated with the combination of the three vitamins either intraperitoneally or orally, respectively, by suspending equivalent amount of vitamins to obtain the same doses per vitamin as mentioned for the preceding treatment groups. On the other hand, systemic liver toxicity was induced by administering APAP (2,800 mg/kg) twice, 9 at days 7 and 8, for all groups except Group I (negative control). At day 9, all rats were sacrificed and blood samples were withdrawn by cardiac puncture and left at room temperature for 15 minutes to clot completely.…”

Section: Methodsmentioning

confidence: 99%

“…ROS induce oxidative stress leading to lipid peroxidation, mitochondrial dysfunction, disruption of calcium, and nitric oxide homeostasis, and finally, cell death by apoptosis and necrosis. 9 …”

Section: Introductionmentioning

confidence: 99%

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Antioxidative stress effects of vitamins C, E, and B<sub>12</sub>, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats

Abdulkhaleq¹,

Alhussainy²,

Badr³

et al. 2018

DDDT

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BackgroundSeveral vitamins, including C, E, and B12, have been recognized as antioxidants and have shown hepatoprotective effects against the hepatotoxicity caused by acetaminophen (APAP) overdose. The current investigation aims to study the effect of these vitamins and their combination in protecting the liver from APAP hepatotoxicity in rats.Materials and methodsAn in vitro model of freshly isolated rat hepatocytes was utilized for assessing hepatocyte mitochondrial activity conducted by cell proliferation assay (MTT). The isolated hepatocytes were treated with vitamin C, vitamin E, vitamin B12 and their combination, with and without further addition of toxic concentrations of APAP. In addition, an in vivo experiment was carried out on Sprague Dawley rats treated intraperitoneally for 8 days with emulsions of the vitamins or their combination prior to injecting them with APAP.ResultsIn vitro results showed that vitamins C and B and the combination preparation significantly increased the percentage of hepatocyte mitochondrial activity, both with and without the addition of APAP (P<0.01). The mitochondrial activity in the isolated cultured hepatocytes was further enhanced with APAP addition. In vivo, the vitamins and their combination effectively reduced APAP-induced serum liver enzymes levels, namely ALT, AST, and ALP, and also attenuated oxidative stress and lipids peroxidation confirmed by the results of glutathione, superoxide dismutase, and maloondialdehyde.ConclusionPretreatment with vitamins C, E, B12, or their combination was found to be beneficial in preventing in vivo hepatic oxidative stress induced by APAP overdose. Vitamin C on its own showed superior protection against APAP-induced liver injury in rats compared to the other vitamins. The proliferation of APAP-intoxicated liver cells in vitro was highest when protected with the vitamins’ combination.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Antioxidative stress effects of vitamins C, E, and B<sub>12</sub>, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats

Abdulkhaleq¹,

Alhussainy²,

Badr³

et al. 2018

DDDT

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“…Glucosamine is also claimed to reduce hepatic metabolism of paracetamol through inhibition of cytochrome P450 metabolizing enzymes, thus it can provide an added advantage to the combination by maximizing the bioavailable fraction of paracetamol. 6 …”

Section: Introductionmentioning

confidence: 99%

Glucosamine-paracetamol spray-dried solid dispersions with maximized intrinsic dissolution rate, bioavailability and decreased levels of in vivo toxic metabolites

Ali¹,

Khames²,

Alrobaian³

et al. 2018

DDDT

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PurposeThis study is aimed at preparing and testing physicochemical, pharmacokinetic and levels of toxic metabolites of paracetamol and glucosamine solid dispersions intended for multiple deliveries via the parenteral or per oral route.MethodsSolid dispersions were prepared using the spray drying technique at different molar ratios of paracetamol and glucosamine. Characterization of the solid dispersions was carried out using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), equilibrium solubility and intrinsic dissolution rate. In vivo pharmacokinetics and toxic metabolites of the prepared dispersions were evaluated and compared to those of pure drugs and physical mixtures.ResultsInstant water solubility and more than 7-fold increase in dissolution rate led to significantly high plasma drug concentration (>6.5-fold) compared to paracetamol alone. More than 2-fold increase in area under the curve from 0 to 24 h from the dispersions was noticed on the third day of oral dosing to animals. Lower number and concentration followed by the complete disappearance of toxic pathway metabolites were observed on second and third days of dosing with solid dispersions and physical mixtures, respectively.ConclusionsThe spray-dried dispersions support safer and more effective delivery of multiple doses of paracetamol, leading to an acceleration of its analgesic actions. Synergism between the analgesic actions of paracetamol and joint protective actions of glucosamine in this combination is expected to facilitate effective treatment of persistent pain-related illnesses such as osteoarthritis.

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“…In the presented work, mice were selected as the animal model of choice to reveal the mechanism by which APAP induces its hepatotoxicity. Mice were previously found more sensitive to APAP toxicity than rats, accounted to alterations in APAP metabolism and protein binding, in addition to differences in mitochondrial dysfunction and oxidative stress between species it has been reported that APAP is capable of inducing hepatotoxicity in rats in a similar manner to that induced in mice when a thr higher dose is employed [17,18].…”

Section: Resultsmentioning

confidence: 99%

Hepatocyte Apoptosis Induction by Acetaminophen Through Modulation of Caspase/Bax Pathway in Mice

Abu-Ajamieh

Ghanim

Gammoh

et al. 2020

Int J Pharm Pharm Sci

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Objective: Acetaminophen (APAP) overdose contributes to liver damage through modulation of pro-apoptotic processing. This study evaluated the involvement of caspase/Bax factors in APAP hepatotoxicity in vivo and in vitro. Methods: The involvement of caspase/Bax factors in APAP hepatotoxicity was evaluated in BALB/c mice and on isolated primary mouse hepatocytes. In vitro MTT assay was carried out on primary cultured mouse hepatocytes treated with APAP (2.5, 5, 10 mmol) and Annexin V/PI staining was employed to cell suspension for imaging under fluorescence microscopy. In addition, caspase-3 concentrations were determined in cell lysates. In vivo, mice were treated with a toxic dose of APAP (700 mg/kg) and immunodetection of Bax was made by Western Blot. Vitamin C (Vit C) was used as a hepato-protectant due to its known antioxidant activities. Results: In vitro dose-dependent increase in mitochondrial electron transport capacity was evident in isolated mouse primary hepatocytes incubated with the high dose of APAP (10 mmol) compared to both nontreated cells and cells pre-treated with Vitamin C (Vit C) (0.5 mmol) (p<0.05). Apoptosis was confirmed in hepatocytes through Annexin V staining after APAP treatment and the signal was reduced when hepatocytes were pre-treated with Vit C. In addition, caspase-3 concentration was decreased in cells pretreated with Vit C prior to APAP exposure. In vivo, Bax immunodetection utilizing western blotting was increased in mice treated with the toxic dose of APAP (700 mg/kg) and attenuated through pre-treatment with Vit C. Conclusion: Modulation of apoptotic caspase/Bax pathway is present in hepatocytes undergoing APAP-induced toxicity.

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Glucosamine Enhances Paracetamol Bioavailability by Reducing Its Metabolism

Cited by 14 publications

References 38 publications

Antioxidative stress effects of vitamins C, E, and B<sub>12</sub>, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats

Antioxidative stress effects of vitamins C, E, and B<sub>12</sub>, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats

Glucosamine-paracetamol spray-dried solid dispersions with maximized intrinsic dissolution rate, bioavailability and decreased levels of in vivo toxic metabolites

Hepatocyte Apoptosis Induction by Acetaminophen Through Modulation of Caspase/Bax Pathway in Mice

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