Doxorubicin (DXR) is widely used in cancer treatment. However, it has not yet been possible to prevent the side effects of DXR. The aim of this study was to investigate the hepatoprotective effect of crocin against DXR used in cancer treatment. For this reason; forty Wistar rats (male-250-300 g) were allocated into four groups (n = 10/group): Control, Crocin, DXR and DXR+Crocin. Control and Crocin groups were administered saline and crocin (40 mg/kg, i.p) for 15 days, respectively. DXR group, cumulative dose 12 mg/kg DXR, was administered for 12 days via 48 h intervals in six injections (2 mg/kg each, i.p). DXR+Crocin group, crocin (40 mg/kg-i.p) was administered for 15 days, and DXR was given as in the DXR group. The results revealed that serum liver markers (alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) increased significantly after DXR administration but recovered after crocin therapy. In addition, lipid peroxidation (MDA), and inflammatory cytokine (TNF-α) increased after DXR application and the antioxidative defense system (GSH, SOD, CAT) significantly decreased and re-achieved by crocin treatment. Our results conclude that crocin treatment was related to ameliorated hepatocellular architecture and reduced hepatic oxidative stress and inflammation in rats with DXR-induced hepatotoxicity.
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http://dx.doi.org/10.1016/j.tice.2023.102182 | DOI Listing |
ACS Med Chem Lett
January 2025
Institute of Pharmaceutical and Medicinal Chemistry, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Multidrug-resistant pathogens pose a major threat to human health, necessitating the identification of new drug targets and lead compounds that are not susceptible to cross-resistance. This study demonstrates that novel reverse thia analogs of the phosphonohydroxamic acid antibiotic fosmidomycin inhibit 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme for , , and that is absent in humans. Some novel analogs with large α-phenyl substituents exhibited strong inhibition across these three DXR orthologues, surpassing the inhibitory activity of fosmidomycin.
View Article and Find Full Text PDFMolecules
December 2024
School of Pharmacy, Kitasato University, Minato-ku, Tokyo 108-8641, Japan.
It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.
View Article and Find Full Text PDFPLoS One
December 2024
Key Laboratory of National Forestry and Grassland Administration for Control of Diseases and Pests of South Plantation, Central South University of Forestry and Technology, Changsha, China.
Agarwood is a precious resinous heartwood highly valued for its cultural, religious, and medicinal significance. With the increasing market demand, natural agarwood resources are rapidly depleting, making the development of effective artificial induction methods for agarwood highly significant. This study aims to explore the feasibility of using callus tissue to assess the ability of fungi to induce agarwood formation.
View Article and Find Full Text PDFBiotechnol Bioeng
December 2024
Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy.
Chondrosarcomas (CHS) constitute approximately 20% of all primary malignant bone tumors, characterized by a slow growth rate with initial manifestation of few signs and symptoms. These malignant cartilaginous neoplasms, particularly those with dedifferentiated histological subtypes, pose significant therapeutic challenges, as they exhibit high resistance to both radiation and chemotherapy. Ranging from relatively benign, low-grade tumors (grade I) to aggressive high-grade tumors with the potential for lung metastases and a grim prognosis, there is a critical need for innovative diagnostic and therapeutic approaches, particularly for patients with more aggressive forms.
View Article and Find Full Text PDFRadiat Prot Dosimetry
December 2024
Former staff of Secondary Standard Dosimetry Laboratory, Centro de Protección e Higiene de la Radiaciones, Carretera La Victoria II Km 2½, e/Monumental y Final, Guanabacoa, La Habana, 11100, Cuba.
The present work describes the results for the bilateral comparison between the Secondary Standards Dosimetry Laboratories of the Instituto Nacional de Investigaciones Nucleares (SSDL-ININ), Mexico, and the pilot laboratory, the Centro de Protección e Higiene de las Radiaciones (SSDL-CPHR), Cuba, for the realization of the air kerma (${\boldsymbol{K}}_{\boldsymbol{a}}$) quantity to: (i) diagnostic X-ray (DXR) IEC 61267:2005 beam qualities: RQR 5 RQR 9, RQT 8, and RQT 9 and (ii) radiation protection (RP) ISO 4037:2019 X-ray beam qualities: N60, N100, and W60, as well S-Cs for gamma radiation. The matched and characterized reference fields are realized at SSDL-ININ with a Toshiba E7252FX X-ray tube. In all cases, the ${\boldsymbol{K}}_{\boldsymbol{a}}$ measurements are traceable to PTB, except for S-Cs, traceable to ININ.
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