Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes acute and chronic peripheral sensory neuropathy, for which no effective treatment has been established. In particular, chronic neuropathy can persist for years even after treatment completion, thus worsening patients' quality of life. To avoid the development of intractable adverse effects, a predictive biomarker early in treatment is awaited.
View Article and Find Full Text PDFJ Neuroinflammation
September 2023
Background: Peripheral nerve injury to dorsal root ganglion (DRG) neurons develops intractable neuropathic pain via induction of neuroinflammation. However, neuropathic pain is rare in the early life of rodents. Here, we aimed to identify a novel therapeutic target for neuropathic pain in adults by comprehensively analyzing the difference of gene expression changes between infant and adult rats after nerve injury.
View Article and Find Full Text PDFPrimary sensory neurons regulate inflammatory processes in innervated regions through neuro-immune communication. However, how their immune-modulating functions are regulated in concert remains largely unknown. Here, we show that Neat1 long non-coding RNA (lncRNA) organizes the proinflammatory gene expressions in the dorsal root ganglion (DRG) in chronic intractable neuropathic pain in rats.
View Article and Find Full Text PDFLipid accumulation in the liver due to chronic alcohol consumption (CAC) is crucial in the development of alcohol liver disease (ALD). It is promoted by the NADH/NAD ratio increase via alcohol dehydrogenase (ADH)-dependent alcohol metabolism and lipogenesis increase via peroxisome proliferator-activated receptor γ (PPARγ) in the liver. The transcriptional activity of PPARγ on lipogenic genes is inhibited by S-nitrosylation but activated by denitrosylation via S-nitrosoglutathione reductase (GSNOR), an enzyme identical to ADH3.
View Article and Find Full Text PDFTranscriptional changes in primary sensory neurons are involved in initiation and maintenance of neuropathic pain. However, the transcription factors in primary sensory neurons responsible for neuropathic pain are not fully understood. Dorsal Root Ganglia Homeobox (DRGX) is a paired-like homeodomain transcription factor necessary for the development of nociceptive primary sensory neurons during the early postnatal period.
View Article and Find Full Text PDFAims: It is still unclear which enzymes contribute to the adaptive enhancement of alcohol metabolism by chronic alcohol consumption (CAC). ADH1 (Class I) has the lowest Km for ethanol and the highest sensitivity for 4-methylpyrazole (4MP) among ADH isozymes, while ADH3 (Class III) has the highest Km and the lowest sensitivity. We investigated how these two major ADHs relate to the adaptive enhancement of alcohol metabolism.
View Article and Find Full Text PDFRheumatoid arthritis (RA)-associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II-induced polyarthritis and anti-cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H ) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species-induced injury implicated in RA pathogenesis.
View Article and Find Full Text PDFBackground: Neuropathic pain is an intractable chronic pain condition caused by damage to the somatosensory system. Although non-coding RNAs such as microRNAs are important regulators of neuropathic pain, the role of long non-coding RNAs (lncRNAs) is poorly understood.
Methods: This study used a rat model of neuropathic pain induced by lumbar fifth spinal nerve ligation (SNL).
Background: Alcohol dehydrogenase 3 (ADH3) plays major roles not only in alcohol metabolism but also in nitric oxide metabolism as S-nitrosoglutathione reductase (GSNOR). ADH3/GSNOR regulates both adipogenesis and osteogenesis through the denitrosylation of peroxisome proliferator-activated receptor γ. The current study investigated the contribution of ADH3 to the development of alcoholic osteoporosis in chronic alcohol consumption (CAC).
View Article and Find Full Text PDFBackground And Aim: Alcohol dehydrogenases (ADHs) 1 and 3 are responsible for systemic alcohol metabolism. The current study investigated the contribution of liver ADH1 and ADH3 to the metabolic pharmacokinetics of chronic alcohol consumption (CAC).
Methods: The 9-week-old male mice of different ADH genotypes (wild-type [WT], Adh1 , and Adh3 ) were administered with 10% ethanol solution for 1 month, followed by acute ethanol administration (4.
miR-17-92 is a microRNA cluster with six distinct members. Here, we show that the miR-17-92 cluster and its individual members modulate chronic neuropathic pain. All cluster members are persistently upregulated in primary sensory neurons after nerve injury.
View Article and Find Full Text PDFBackground And Purpose: Although oxaliplatin is an effective anti-cancer platinum compound, it can cause painful chronic neuropathy, and its molecular mechanisms are poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression in a sequence-specific manner. Although miRNAs have been increasingly recognized as important modulators in a variety of pain conditions, their involvement in chemotherapy-induced neuropathic pain is unknown.
View Article and Find Full Text PDFSeveral drug-metabolizing cytochrome P450 (CYP) enzymes exhibit sexual dimorphism depending on the pituitary growth hormone (GH) secretory patterns. However, the mechanism underlying CYP sexual dimorphism remains unclear. We previously established a transgenic (Alb-DsRed2 Tg) rat that expressed red fluorescent DsRed2 protein, particularly in hepatocytes, to visualize cell differentiation and multiplication and found that hepatic DsRed2 expression exhibited sexual dimorphism that was limited to adult males.
View Article and Find Full Text PDF