Safety and Mode of Action of Diabetes Medications in comparison with 5-Aminolevulinic Acid (5-ALA)

Rehani, Peter; Iftikhar, Hanaa; Nakajima, Motowo; Tanaka, Tohru; Jabbar, Zaid; Rehani, Riyadh

doi:10.1155/2019/4267357

Cited by 29 publications

(24 citation statements)

References 45 publications

(38 reference statements)

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“…We calculated the approximate expression of the histopathological score (y, a dose-dependent parameter in the pharmacological evaluation of micro miniature pigs) and the approximate expression of 5-ALA (x) in blood 1.5 h after administration of 5-ALA with the following equation: y = -0.128 ln(x) + 4.2958 (1). Furthermore, when we plotted the 5-ALA dose (a) and 5-ALA levels in blood (b) 1 h after administration in humans, using data from a phase 1 study, we approximated the following function: b = f (a) …(2) (unpublished data).…”

Section: Calculation Of the Hedmentioning

confidence: 99%

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Predicting the Effective Dose of 5-Aminolevulinic Acid to Protect Humans From Renal Ischemia-Reperfusion Injury: A Study in Micro Miniature Pigs

Fujine¹,

Sano

Katsumata

et al. 2021

J Curr Surg

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Background: In rodent models, 5-aminolevulinic acid (5-ALA) was shown to prevent renal ischemia-reperfusion injury, but the data did not allow estimation of the human equivalent dose (HED). Therefore, this study evaluated the renal effects of 5-ALA and estimated the HED in micro miniature pigs, which have a metabolism closer to that of humans. Methods: We analyzed the efficacy and pharmacokinetics of 5-ALA by administering it to nine micro miniature pigs 2 days before renal ischemia-reperfusion injury. A pathological score was calculated on the basis of renal tissue damage; the blood concentration of 5-ALA required to prevent damage was estimated from the expected pathological score by back-calculating it from the obtained approximate expression. The pharmacokinetics data obtained in phase 1 human trials (5-ALA dose vs. blood concentration curve) were used to calculate the HED. Results: Dose-dependent improvement in tissue damage (rated as a pathological score) was confirmed 7 days after reperfusion. In each animal, the blood concentrations of 5-ALA correlated with the pathological score. We estimated that doses of approximately 1.6 mg/kg and 13.4 mg/kg would be required to obtain histopathology scores of 4 and 3.7 in humans, respectively. Conclusions: This is the first study to show that the HED of 5-ALA can be calculated from efficacy and pharmacokinetics data obtained in micro miniature pigs.

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Section: Calculation Of the Hedmentioning

confidence: 99%

“…5-ALA has been introduced into health foods with the aim to achieve beneficial effects in several human diseases related to abnormal energy metabolism [1,2]; however, the effects of 5-ALA vary depending on its concentration. At low concentrations (2.5 mg/kg), 5-ALA is effective in activating the electron transport system of mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Predicting the Effective Dose of 5-Aminolevulinic Acid to Protect Humans From Renal Ischemia-Reperfusion Injury: A Study in Micro Miniature Pigs

Fujine¹,

Sano

Katsumata

et al. 2021

J Curr Surg

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“…There is general agreement that ROS production is essential to elicit the therapeutic effects of 5-ALA-mediated PDT [ 164 ]. Importantly, 5-ALA is produced and located in the mitochondria; therefore, exogenously supplemented 5-ALA can modulate mitochondrial functions [ 165 ]. PDT with 5-ALA reduced mROS levels and, subsequently, the mROS-dependent autophagy pathway was suppressed in keloids [ 164 ].…”

Section: Photodynamic Therapymentioning

confidence: 99%

Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

et al. 2020

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Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.

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“…Heme functions in various kinds of physiological processes by composing protein complexes such as cytochromes. As 5-ALA enhances aerobic energy metabolism, it has been clinically used for metabolic improvement in human diseases including diabetes [ 6 ]. Moreover, utilizing a photosensitive feature of PPIX, 5-ALA has also been used for diagnosis and therapy for various cancers, suggesting the benefits of 5-ALA in many fields of human health [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

Sakurai

Tun

Kurosaki

et al. 2021

Biochemical and Biophysical Research Communications

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Safety and Mode of Action of Diabetes Medications in comparison with 5-Aminolevulinic Acid (5-ALA)

Cited by 29 publications

References 45 publications

Predicting the Effective Dose of 5-Aminolevulinic Acid to Protect Humans From Renal Ischemia-Reperfusion Injury: A Study in Micro Miniature Pigs

Predicting the Effective Dose of 5-Aminolevulinic Acid to Protect Humans From Renal Ischemia-Reperfusion Injury: A Study in Micro Miniature Pigs

Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

5-amino levulinic acid inhibits SARS-CoV-2 infection in vitro

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