John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used

Pillai, Sadasivan Kalathil; Kobayashi, Kazuo; Michael, Mathews; Mathai, Thomson; Sivakumar, Bhavana; Sadasivan, Parvathy

doi:10.26444/jpccr/139588

Cited by 16 publications

(5 citation statements)

References 11 publications

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“…The LD50 was computed using a linear equation and came out to be 5.656g/kg. The results showed a very tiny gain in weight in comparison to mice in the control group, which could be attributed to the oil's toxicity, but the difference in weight between groups is not significant (P ˃0.05) when compared to their control group (Pillai et al, 2021). In their study, Kaithwas et al(2011) found no change in body weight in rats given flaxseed oil intraperitoneally, and this observation is in agreement with the findings of the current investigation into acute toxicity.…”

Section: Discussionmentioning

confidence: 84%

The Antiangiogenic Activity of Flaxseed Oil Alone and Combination with Mefenamic Acid in Vivo and in Vitro Assay

Al-Zubaidy

Sahib

2022

Asian Pac J Cancer Prev

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Background: Antiangiogenic agents are commonly used for the management of many types of cancers. Flaxseed oil is a wealthy source of omega-3,omega-6, and lignans, and possesses anticancerous and antioxidant activities. Objective: To investigate the antiangiogenic activity of flaxseed oil alone and in combination with mefenamic acid in a dose-response study. Methods: Oil was extracted from flaxseeds. The ex vivo rat aorta ring assay was used to screen the flaxseed oil alone and in combination with mefenamic acid for possible antiangiogenic activity. Also, the assay was used to determine the dose-response effect.An in vivo chick chorioallantoic membrane (CAM) assay was used to quantify the zone of inhibition of blood vessel by flaxseed oil. Results: The 200,100,50,25,12.5, and 6.25µg/ ml of the flaxseed oil inhibited blood vessel growth with values of 91±0.42, 84±2.06,36±2.71, 21±2.15,23±1.56, and 5±0.93%, respectively, withan IC 50 value of 45.695 µg/ml. These concentrations showed a dose-dependent inhibition of angiogenesis. At 200, 100, and 50 µg/ml of flaxseed oil in combination with 50 µg/ml of mefenamic acid inhibited blood vessel growth with inhibition percentages of 81.48±0.82,79.63±0.75, and 77.78±1.26, respectively, with an IC 50 of 2.27 µg/ml. Also, these concentrations indicated a dose-dependent inhibition of angiogenesis. Flaxseed oil produced a significant inhibition zone of blood vessels in the CAM assay. The LD 50 for flaxseed oil was 5.656g/kg. Conclusion: Flaxseed oil alone and in combination with mefenamic acid exhibited antiangiogenic activity both in ex vivo and in vivo assays. At doses of 2.5, 1.25, 0.625, and 0.312 g/kg of flaxseed oil intraperitoneally injected into mice, no symptoms of toxicity or death of mice due to acute toxicity were observed. However, doses of 5 and 10 g/kg of oil resulted in the death of the majority of mice.

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Section: Discussionmentioning

confidence: 84%

The Antiangiogenic Activity of Flaxseed Oil Alone and Combination with Mefenamic Acid in Vivo and in Vitro Assay

Al-Zubaidy

Sahib

2022

Asian Pac J Cancer Prev

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“…Both compounds were also evaluated to predict their toxicity with Pro-Tox II software to determine the LD 50 prediction. The LD 50 prediction of both compounds is essential in future research using doses in vivo assay (Pillai et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

CHARACTERIZATION OF ANTIOXIDANT COMPOUNDS FROM CELEBES SEA BAMBOO EXTRACTS (Isis hippuris) USING GC-MS

Tanod,

Dewanto,

Cahyono

et al. 2023

JPK UNTIRTA

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Sea bamboo (Isis hippuris) is one of the octocorallia classes that has unique biological activity and is beneficial for pharmaceutical development. Evaluation of bioactive compounds from sea bamboo collected from Sulawesi (Celebes) waters has been previously reported but lacks information. Gas chromatography and mass spectrometry (GC-MS) are one of the instruments used to evaluate bioactive compounds. This study aims to evaluate bioactive compounds from extracts of sea bamboo from Sulawesi by GC-MS, analyze their antioxidant properties using the DPPH method, and predict their activity computationally using PASS. Samples of sea bamboo were collected from Kabonga Besar Coast, Palu Bay, Central Sulawesi, Indonesia. Samples were extracted by maceration method using methanol: dichloromethane solvent (1:1). GC-MS evaluation identified six alkaloid-derived compounds, namely tetramethyldiaminoethane, dimethylisopropanolamine, 2,4-dimethylpyrrole, 1-(carboxymethyl)pyridinium chloride, pyridine, 3,4-dimethyl-, and N-nitroso-2-methylthiazolidine. The Celebes sea bamboo extracts have potent antioxidant activity. Tetramethyldiaminoethane and dimethylisopropanolamine compounds are predicted to have antioxidant abilities closely related to their role as NADPH-oxidase inhibitors.

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“…One of the most important factors that must be taken into account when researching drugs is to determine the median lethal dose (20), through which you will have an idea of the doses that can be used. We determined the median lethal dose of flurbiprofen using the up-and-down method, which is considered the most ethical method in this approach because a minimum number of animals have been used compared with other approaches (21).…”

Section: Discussionmentioning

confidence: 99%

Flurbiprofen: Determination of safety profile, analgesic effect, and interaction with lipoic acid in murine

Alberifki¹,

Naser²

2023

IJVS

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our study aimed study aimed to detect and investigate the safety profile of flurbiprofen and evaluate the analgesic effects of the tail immersion and writhing tests, as well as its interaction with lipoic acid as an analgesic for visceral pain in mice. The up-and-down manner described by Dixon was utilized to determine the median lethal dose (LD50) and the median analgesic dose (ED50), the safety criteria were calculated, mathematical equations were applied, and the interaction between flurbiprofen and alpha-lipoic acid was evaluated using the writhing test. The LD50 of oral flurbiprofen was 1147.4 mg/kg, and the ED50 of oral flurbiprofen was 8.6 mg/kg using the tail immersion test. The therapeutic index was 133, and the standard safety margin was 35%. The highest analgesia time was one h after dosing, which faded after 24 h. Administration of flurbiprofen 10, 20, and 40 mg/kg had an analgesic effect in a dose-dependent manner. Flurbiprofen relieved visceral pain when dosed at 20, 40, and 80 mg/kg, with analgesic efficacies of 53, 56, and 65%, respectively. The simultaneous administration of flurbiprofen and alpha-lipoic acid had a synergistic analgesic effect on visceral pain. From our results, we conclude that flurbiprofen has a wide range of safety and is an effective analgesic for peripheral and visceral pain. The synergistic effect between flurbiprofen and alpha-lipoic acid may have clinical benefits, including reducing the dose of flurbiprofen when used together.

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John William Trevan’s concept of Median Lethal Dose (LD50/LC50) – more misused than used

Cited by 16 publications

References 11 publications

The Antiangiogenic Activity of Flaxseed Oil Alone and Combination with Mefenamic Acid in Vivo and in Vitro Assay

The Antiangiogenic Activity of Flaxseed Oil Alone and Combination with Mefenamic Acid in Vivo and in Vitro Assay

CHARACTERIZATION OF ANTIOXIDANT COMPOUNDS FROM CELEBES SEA BAMBOO EXTRACTS (Isis hippuris) USING GC-MS

Flurbiprofen: Determination of safety profile, analgesic effect, and interaction with lipoic acid in murine

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