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Uptake of Fluorescein via a pH-Dependent Monocarboxylate Transporter by Human Kidney 2 (HK-2) Cells
Biol Pharm Bull. 2024;47(1):79-87. doi: 10.1248/bpb.b23-00570.ABSTRACTHerein, we investigated whether a fluorescent probe for an organic anion transporter (OAT), fluorescein (FLS), could be accumulated by human kidney 2 (HK-2) cells derived from human kidney proximal tubular epithelia. HK-2 cells took up FLS in a pH-dependent and concentration-dependent manner. FLS accumulation by HK-2 cells was inhibited by monocarboxylic acids, ibuprofen, rosuvastatin, and indoleacetic acid but not by typical substrates for OATs. A typical protonophore, carbonyl cyanide p-trichloromethoxyphenylhydrazone completely abolished FLS accumulat...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Takaharu Takiguchi Kazuaki Sugio Masayuki Masuda Shotaro Sasaki Seiji Miyauchi Source Type: research

Clinical Profiles of Japanese Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Collected by a Nationwide System from 2006 to 2023
This study evaluated the associations of clinical symptoms with sequelae and specific causative drugs/drug groups in Japanese patients with SJS/TEN to identify clinical clues for SJS/TEN treatment and prognosis. Acetaminophen, antibiotics, and carbocisteine were linked to high frequencies of severe ocular symptoms and ocular sequelae (p < 0.05). For erythema and erosion areas, antipyretic analgesics had higher rates of skin symptom affecting <10% of the skin than the other drugs, suggesting narrower lesions (p < 0.004). Hepatic dysfunction, was common in both SJS and TEN, and antiepileptic drugs carried higher ris...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Eri Tsukagoshi Ryosuke Nakamura Nahoko Kaniwa Kimie Sai Ruri Kikura-Hanajiri Kayoko Matsunaga Riichiro Abe Hideo Asada Yoshiro Saito Source Type: research

Risk Evaluation of Proton Pump Inhibitors for Panitumumab-Related Hypomagnesemia in Patients with Metastatic Colorectal Cancer
Biol Pharm Bull. 2024;47(1):98-103. doi: 10.1248/bpb.b23-00641.ABSTRACTHypomagnesemia commonly occurs as a side effect of panitumumab treatment. In severe cases, temporary discontinuation or dose reduction of panitumumab may be necessary. Proton pump inhibitors (PPIs) are reportedly potential risk factors for hypomagnesemia. We conducted a multicenter study to assess the impact of PPIs on the risk of grade 3-4 hypomagnesemia in patients with metastatic colorectal cancer (mCRC) receiving panitumumab. We adjusted for potential bias using a propensity score-matched analysis and retrospectively reviewed the medical records of ...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Hideyuki Katsura Yukio Suga Anna Kubo Hayato Sugimura Kaname Kumatani Kazunobu Haruki Miwa Yonezawa Ayaka Narita Rei Ishijima Hiroaki Ikesue Hitomi Toi Naoko Takata Source Type: research

Physiological and Pathological Significance of Chloride Channels
Biol Pharm Bull. 2024;47(1):1-13. doi: 10.1248/bpb.b23-00820.ABSTRACTCl- influx and efflux through Cl- channels play a role in regulating the homeostasis of biological functions. Therefore, the hyperfunction or dysfunction of Cl- channels elicits pathological mechanisms. The Cl- channel superfamily includes voltage-gated Cl- (ClC) channels, Ca2+-activated Cl- channels (ClCa; TMEM16A/TMEM16B), cystic fibrosis transmembrane conductance regulator channels, and ligand-gated Cl- channels. These channels are ubiquitously expressed to regulate ion homeostasis, muscle tonus, membrane excitability, cell volume, survival, neurotrans...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Hisao Yamamura Source Type: research

Ethoxyquin, a Lipid Peroxidation Inhibitor, Has Protective Effects against White Matter Lesions in a Mouse Model of Chronic Cerebral Hypoperfusion
In this study, we investigated lipid peroxidation, which has recently been pointed out to be associated with cerebrovascular disease and vascular dementia, as a therapeutic target for chronic cerebral hypoperfusion. We used ethoxyquin, a lipid-soluble antioxidant, in a neuronal cell line and mouse model of the disease. The cytoprotective effect of ethoxyquin on glutamate-stimulated HT-22 cells, a mouse hippocampal cell line, was comparable to that of a ferroptosis inhibitor. In addition, the administration of ethoxyquin to bilateral common carotid artery stenosis model mice suppressed white matter lesions, blood-brain barr...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Masami Abe Marie Sou Yuta Matsuoka Kazushi Morimoto Ken-Ichi Yamada Source Type: research

New Maintenance Culture Method for Intestinal Stem Cells Derived from Human Induced Pluripotent Stem Cells
Biol Pharm Bull. 2024;47(1):120-129. doi: 10.1248/bpb.b23-00573.ABSTRACTMost orally administered drugs exert their effects after being absorbed in the small intestine. Therefore, new drugs must undergo nonclinical pharmacokinetic evaluations in the small intestine. Enterocytes derived from human induced pluripotent stem cells (hiPSCs) are expected to be used in the evaluation system, as they reflect human intestinal characteristics more accurately; moreover, several differentiation protocols are available for these cells. However, enterocytes derived from hiPSCs have drawbacks such as time, cost, and lot-to-lot differences...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Shota Mizuno Yumi Jinnoh Ayaka Arita Shimeng Qiu Tadahiro Hashita Eisei Hori Takahiro Iwao Tamihide Matsunaga Source Type: research

Goji Berry Juice Prevents Tumor Necrosis Factor Alpha-Induced Xerostomia in Human Salivary Gland Cells
Biol Pharm Bull. 2024;47(1):138-144. doi: 10.1248/bpb.b23-00456.ABSTRACTSjögren's syndrome (SS) is an autoimmune disorder characterized by oral dryness that is primarily attributed to tumor necrosis factor alpha (TNF-α)-mediated reduction in saliva production. In traditional Chinese medicine, goji berries are recognized for their hydrating effect and are considered suitable to address oral dryness associated with Yin deficiency. In the present study, we used goji berry juice (GBJ) to investigate the potential preventive effect of goji berries on oral dryness caused by SS. Pretreatment of human salivary gland cells with G...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Masatoshi Takakura Ayano Mizutani Mizuki Kudo Airi Ishikawa Takuya Okamoto Tong Xuan Fu Shin-Ichiro Kurimoto Yuka Koike Kenji Mishima Junichi Tanaka Tomio Inoue Kazuyoshi Kawazoe Source Type: research

Oleic Acid Activates Mitochondrial Energy Metabolism and Reduces Oxidative Stress Resistance in the Pancreatic β-Cell Line INS-1
In this study, we examined the effects of oleic acid (OA), a monounsaturated fatty acid, on mitochondrial function, which is important for insulin secretion, using INS-1 cells, a pancreatic β-cell line derived from rats. Observations of mitochondrial membrane potential and intracellular ATP concentration showed that the electron transport chain was enhanced and ATP production increased in cells treated with OA, indicating that the response that occurs from sensing an increase in glucose concentration to the production of ATP was accelerated. Measurements of intracellular reactive oxygen species (ROS) indicated that the ra...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Mariko Suzuki Kaoruko Endo Riko Nagata Naoko Iida-Tanaka Source Type: research

Regulation of Chloride Channels by Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Induced α-Defensin 5
Biol Pharm Bull. 2024;47(1):159-165. doi: 10.1248/bpb.b23-00672.ABSTRACTEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat non-small cell lung cancer with EGFR mutations. However, first-generation erlotinib and second-generation afatinib often cause diarrhea, which may develop because of the association between EGFR-TKIs and the chloride channel or abnormalities in the intestinal microbiota due to disruption of the intestinal immune system. As reports on the effects of EGFR-TKIs on intestinal immunity are lacking, we aimed to determine whether the intestinal immune system is involved ...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Ippei Uemura Natsuko Takahashi-Suzuki Fumiya Kita Masaki Kobayashi Takehiro Yamada Ken Iseki Takashi Satoh Source Type: research

Unique Behavior of Bacterially Expressed Rat Carnitine Palmitoyltransferase 2 and Its Catalytic Activity
Biol Pharm Bull. 2024;47(1):23-27. doi: 10.1248/bpb.b23-00612.ABSTRACTMammalian type 2 carnitine parmitoyltransferase (EC 2.3.1.21), abbreviated as CPT2, is an enzyme involved in the translocation of fatty acid into the mitochondrial matrix space, and catalyzes the reaction acylcarnitine + CoA = acyl-CoA + carnitine. When rat CPT2 was expressed in Escherichia coli, its behavior was dependent on the presence or absence of i) its mitochondrial localization sequence and ii) a short amino acid sequence thought to anchor it to the mitochondrial inner membrane: CPT2 containing both sequences behaved as a hydrophobic protein, whi...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Kiri Akieda Kazuto Takegawa Takeshi Ito Gaku Nagayama Naoshi Yamazaki Yuka Nagasaki Kohei Nishino Hidetaka Kosako Yasuo Shinohara Source Type: research

Identification of Azalamellarin N as a Pyroptosis Inhibitor
Biol Pharm Bull. 2024;47(1):28-36. doi: 10.1248/bpb.b23-00569.ABSTRACTPyroptosis is a form of regulated cell death that promotes inflammation; it attracts much attention because its dysregulation leads to various inflammatory diseases. To help explore the precise mechanisms by which pyroptosis is regulated, in this study, we searched for chemical compounds that inhibit pyroptosis. From our original compound library, we identified azalamellarin N (AZL-N), a hexacyclic pyrrole alkaloid, as an inhibitor of pyroptosis induced by R837 (also called imiquimod), which is an agonist of the intracellular multiprotein complex nucleot...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Jun Takouda Moeka Nakamura Akane Murasaki Waka Shimosako Aoi Hidaka Shino Honda Susumu Tanimura Fumito Ishibashi Norihiko Kawasaki Jun Ishihara Tsutomu Fukuda Kohsuke Takeda Source Type: research

Vildagliptin Treatment Ameliorates Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction
Biol Pharm Bull. 2024;47(1):37-42. doi: 10.1248/bpb.b23-00609.ABSTRACTRenal interstitial fibrosis in mice can be modeled using unilateral ureteral obstruction (UUO). Here, we investigated the anti-fibrotic effects of the dipeptidyl peptidase-4 inhibitor vildagliptin in this model. We found that vildagliptin given in the drinking water at 10.6 ± 1.5 mg/kg/d prevented fibrosis. Mechanistically, UUO was associated with extracellular signal-regulated kinase (ERK) phosphorylation and with the accumulation of the toxic lipid peroxidation product expression of 4-hydroxy-2-nonenal (4-HNE). Both were significantly inhibited by vil...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Shigeyoshi Honma Sota Kakuage Yuta Morita Takeki Ito Makoto Yoshida Source Type: research

Expression of Epithelial-Mesenchymal Transition Markers in Epidermal Layer of Atopic Dermatitis
Biol Pharm Bull. 2024;47(1):49-59. doi: 10.1248/bpb.b23-00291.ABSTRACTThe epithelial-mesenchymal transition (EMT) is a phenomenon, in which epithelial cells acquire a mesenchymal cell phenotype. It is important during wound healing; however, chronic inflammation leads to excessive EMT and causes tissue barrier dysfunction with hyperplasia. EMT is induced by several cytokines, such as interleukin (IL)-4 and IL-13. Additionally, IL-4 and IL-13 are known to increase in atopic dermatitis (AD) characterized by intense itching and eczema. Therefore, we assumed that there was commonality between the respective EMT and AD phenotyp...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Kazuyuki Kitazawa Kazunori Tanaka Yoshiki Kubota Mina Musashi Kiyoshi Higashi Teruaki Nagasawa Miyuki Kobayashi Tatsuro Kamakura Rie Igarashi Yoko Yamaguchi Source Type: research

Magnitude of Fruit Juice-Drug Interactions Due to Osmolality-Dependent Fluid Secretion: Differences among Apple, Orange, and Grapefruit Juices
Biol Pharm Bull. 2024;47(1):72-78. doi: 10.1248/bpb.b23-00490.ABSTRACTWe recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively. Measurements of i...
Source: Biological and Pharmaceutical Bulletin - January 3, 2024 Category: Drugs & Pharmacology Authors: Miyuki Takemura Katsuhisa Inoue Ikumi Tamai Yoshiyuki Shirasaka Source Type: research