Background: Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. Thiamine pyrophosphate (TPP) to be investigated for its effect on cyclophosphamide-induced ovarian damage and reproductive dysfunction in the present study is the active metabolite of thiamine. It has been shown that TPP protects organs and tissues from oxidative stress and proinflammatory cytokine damage.
Objectives: To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats.
Material And Methods: Albino Wistar type female rats were divided into healthy control (HG), cyclophosphamide (CYC) and TPP + cyclophosphamide (TPPC) groups (for each group, n = 12). Thiamine pyrophosphate at a dose of 25 mg/kg was injected intraperitoneally (ip.) in the TPPC group, and 0.9% NaCI solution was injected ip. in the CYC and HG groups. One hour after the injection, 75 mg/kg of cyclophosphamide was administered ip. in the TPPC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, 6 rats from each group were euthanized with a high dose of anesthetic (50 mg/kg of sodium thiopental). Biochemical and histopathological examinations were performed on the extracted ovarian tissue. The remaining animals were kept in the laboratory with mature male rats for 2 months for reproduction.
Results: Thiamine pyrophosphate significantly decreased the cyclophosphamide-induced increase in the levels of the oxidant parameter malondialdehyde (MDA), proinflammatory nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β). In addition, TPP decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility.
Conclusions: Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.
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http://dx.doi.org/10.17219/acem/142535 | DOI Listing |
Nanoscale
December 2024
Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Atherosclerosis is the main pathogenic factor of various cardiovascular diseases. During the pathogenesis of atherosclerosis, macrophages play a major role, mainly by secreting pro-inflammatory cytokines and taking in lipids to form foam cells. Thiamine pyrophosphate (TPP) is an antagonist of the P2Y6 receptor, which is overexpressed on macrophages during atherosclerosis and facilitates the lipid phagocytosis of macrophages.
View Article and Find Full Text PDFInorg Chem
December 2024
Department of Laboratory Medicine/Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Monitoring acetylcholinesterase (AChE) activity and its inhibitor is crucial yet challenging for the early diagnosis and treatment of neurological diseases. In this study, we present Au nanoparticle decorated CoAl layered double hydroxide monolayer (Au@CoAl-LDH-m) as a peroxidase-like (POD) nanozyme for the sensitive colorimetric detection of AChE and its inhibitor, thiamine pyrophosphate (TPP). Remarkably, the Au@CoAl-LDH-m nanozyme can catalyze the oxidation of chromogenic substrates through its POD-like activity, which is effectively inhibited by thiocholine (TCh, a catalytic product of AChE), thereby enabling detection of AChE and TPP through a visible colorimetric readout.
View Article and Find Full Text PDFBiochemistry
December 2024
Department of Life Science, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.
The RhiE and RhiF proteins work together as RhiEF and function as a thiamine pyrophosphate (TPP)-dependent phosphonopyruvate decarboxylase to produce phosphonoacetaldehyde in the rhizocticin biosynthesis pathway. In this study, we determined the crystal structure of the RhiEF complexed with TPP and Mg. RhiEF forms a dimer of heterodimers, and the cofactor TPP is bound at the heterotetrameric subunit interface.
View Article and Find Full Text PDFBioresour Bioprocess
November 2024
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96-12.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Research School of Biology, The Australian National University, Canberra, Australia.
Thiamine is metabolized into thiamine pyrophosphate (TPP), an essential enzyme cofactor. Previous work has shown that oxythiamine, a thiamine analog, is metabolized by thiamine pyrophosphokinase (TPK) into oxythiamine pyrophosphate within the malaria parasite and then inhibits TPP-dependent enzymes, killing the parasite and . To identify a more potent antiplasmodial thiamine analog, 11 commercially available compounds were tested against and .
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