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1.
J Coll Physicians Surg Pak ; 34(6): 641-645, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840343

ABSTRACT

OBJECTIVE: To determine the preventive effect of coenzyme Q10 (CoQ10) on the testicular histology of rats exposed chronically to mosquito coil smoke. STUDY DESIGN: Experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College/National University of Medical Sciences, Rawalpindi, Pakistan, from January to December 2020. METHODOLOGY: Thirty male Sprague Dawley rats were divided into three groups of 10 rats each. Group A was the healthy control. Group B rats were exposed to allethrin-based mosquito coil smoke for 12 weeks (4 hours/day). Group C rats received coenzyme Q10 (CoQ10, 10mg/kg/day) through oral gavage, in addition to 12 weeks of mosquito coil smoke exposure (4 hours/day). At the end of the study, testicular histology was compared among three groups including the germinal epithelium height, seminiferous tubule diameter, and testicular capsule thickness, while adjusting for the body weight variations among rats. RESULTS: The rats in Group B, exposed only to mosquito coil smoke showed testicular disruption, characterised by dilated seminiferous tubules (p <0.001), reduced germinal epithelial height (p <0.001), and thickened testicular capsule (p <0.007), as compared to the control group rats. However, the germinal epithelium height (p = 0.73) and testicular capsule thickness (p = 0.31) of rats receiving CoQ10 in addition to mosquito coil smoke inhalation were not significantly different from the control group. CONCLUSION: Prolonged inhalation of allethrin-based mosquito coil smoke can cause testicular disruption among rats. The oral CoQ10 administration can effectively prevent the histomorphological adverse effects on the testis among rats exposed to mosquito coil smoke. KEY WORDS: Allethrin, Coenzyme Q10, Germinal epithelium, Mosquito coil, Seminiferous tubules, Testicular capsule.


Subject(s)
Rats, Sprague-Dawley , Testis , Ubiquinone , Animals , Male , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquinone/administration & dosage , Rats , Testis/drug effects , Testis/pathology , Smoke/adverse effects , Allethrins/pharmacology , Smoke Inhalation Injury/prevention & control , Smoke Inhalation Injury/pathology
2.
Rev Assoc Med Bras (1992) ; 70(4): e20230990, 2024.
Article in English | MEDLINE | ID: mdl-38716935

ABSTRACT

OBJECTIVE: We aimed to investigate the effect of coenzyme q10 on cyclophosphamide-induced kidney damage in rats. METHODS: A total of 30 female Wistar-Albino rats were utilized to form three groups. In group 1 (control group) (n=10), no drugs were given. In group 2 (cyclophosphamide group) (n=10), 30 mg/kg intraperitoneal cyclophosphamide was administered for 7 days. In group 3 (cyclophosphamide+coenzyme q10 group) (n=10), 30 mg/kg cyclophosphamide and 10 mg/kg coenzyme q10 were given for 7 days via intraperitoneal route. Right kidneys were removed in all groups. Blood malondialdehyde levels and activities of catalase and superoxide dismutase were measured. Histopathological damage was evaluated by examining the slides prepared from kidney tissue using a light microscope. RESULTS: Tissue damage was significantly higher in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). The malondialdehyde levels were significantly higher and the activities of superoxide dismutase and catalase were lower in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). CONCLUSION: Coenzyme q10 may be a good option to prevent cyclophosphamide-induced kidney damage.


Subject(s)
Catalase , Cyclophosphamide , Malondialdehyde , Rats, Wistar , Superoxide Dismutase , Ubiquinone , Animals , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Cyclophosphamide/toxicity , Cyclophosphamide/adverse effects , Female , Catalase/metabolism , Superoxide Dismutase/metabolism , Superoxide Dismutase/drug effects , Kidney/drug effects , Kidney/pathology , Rats , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Kidney Diseases/pathology , Antioxidants/pharmacology , Oxidative Stress/drug effects
3.
Nat Commun ; 15(1): 3367, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719808

ABSTRACT

Soil-transmitted helminths (STHs) are major pathogens infecting over a billion people. There are few classes of anthelmintics and there is an urgent need for new drugs. Many STHs use an unusual form of anaerobic metabolism to survive the hypoxic conditions of the host gut. This requires rhodoquinone (RQ), a quinone electron carrier. RQ is not made or used by vertebrate hosts making it an excellent therapeutic target. Here we screen 480 structural families of natural products to find compounds that kill Caenorhabditis elegans specifically when they require RQ-dependent metabolism. We identify several classes of compounds including a family of species-selective inhibitors of mitochondrial respiratory complex I. These identified complex I inhibitors have a benzimidazole core and we determine key structural requirements for activity by screening 1,280 related compounds. Finally, we show several of these compounds kill adult STHs. We suggest these species-selective complex I inhibitors are potential anthelmintics.


Subject(s)
Anthelmintics , Caenorhabditis elegans , Electron Transport Complex I , Ubiquinone/analogs & derivatives , Animals , Anthelmintics/pharmacology , Anthelmintics/chemistry , Electron Transport Complex I/antagonists & inhibitors , Electron Transport Complex I/metabolism , Caenorhabditis elegans/metabolism , Benzimidazoles/pharmacology , Benzimidazoles/chemistry , Species Specificity , Quinones/chemistry , Quinones/pharmacology , Quinones/metabolism , Biological Products/pharmacology , Biological Products/chemistry
4.
Article in English | MEDLINE | ID: mdl-38728177

ABSTRACT

Two Gram-stain-negative, rod-shaped bacteria, designated as strains KJ10-1T and KJ40-1T, were isolated from marine brown algae. Both strains were catalase-positive, oxidase-positive, and facultative aerobic. Strain KJ10-1T exhibited optimal growth at 25 °C, pH 7.0, and 3 % NaCl, whereas strain KJ40-1T showed optimal growth at 25 °C, pH 7.0, and 2 % NaCl. The respiratory quinones of strain KJ10-1T were ubiquinone-8, ubiquinone-7, menaquinone-7, and methylated menaquinone-7, while the respiratory quinone of strain KJ40-1T was only ubiquinone-8. As major fatty acids, strain KJ10-1T contained C16 : 0, C17 : 1 ω8c, iso-C15 : 0, and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and strain KJ40-1T contained C16 : 0 and summed features 3 and 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The major polar lipids in strain KJ10-1T were phosphatidylethanolamine, phosphatidylglycerol, and an unidentified aminolipid, whereas those in strain KJ40-1T were phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol. The DNA G+C contents of strains KJ10-1T and KJ40-1T were 42.1 and 40.8 mol%, respectively. Based on 16S rRNA gene sequences, strains KJ10-1T and KJ40-1T exhibited the closest relatedness to Shewanella saliphila MMS16-UL250T (98.6 %) and Vibrio rumoiensis S-1T (95.4 %), respectively. Phylogenetic analyses, based on both 16S rRNA and 92 housekeeping genes, showed that the strains formed distinct phylogenic lineages within the genera Shewanella and Vibrio. Digital DNA-DNA hybridization and orthologous average nucleotide identity values between strain KJ10-1T and other Shewanella species, as well as between strain KJ40-1T and other Vibrio species, were below the thresholds commonly accepted for prokaryotic species delineation. Based on the phenotypic, chemotaxonomic, and phylogenetic data, strains KJ10-1T and KJ40-1T represent novel species of the genera Shewanella and Vibrio, respectively, for which the names Shewanella phaeophyticola sp. nov. and Vibrio algarum sp. nov. are proposed, respectively. The type strains of S. phaeophyticola and V. algarum are KJ10-1T (=KACC 22589T=JCM 35409T) and KJ40-1T (=KACC 22588T=JCM 35410T), respectively.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Phaeophyceae , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Shewanella , Ubiquinone , Vibrio , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Vibrio/genetics , Vibrio/classification , Vibrio/isolation & purification , Ubiquinone/analogs & derivatives , Shewanella/genetics , Shewanella/isolation & purification , Shewanella/classification , Phaeophyceae/microbiology , Vitamin K 2/analogs & derivatives , Phospholipids , Nucleic Acid Hybridization , Seawater/microbiology
5.
Article in English | MEDLINE | ID: mdl-38728178

ABSTRACT

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0-7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Stomach , RNA, Ribosomal, 16S/genetics , Fatty Acids/chemistry , Humans , DNA, Bacterial/genetics , Stomach/microbiology , Nucleic Acid Hybridization , Ubiquinone , Phospholipids/chemistry
6.
Article in English | MEDLINE | ID: mdl-38728208

ABSTRACT

A Gram-stain-negative and rod-shaped bacterium, designated strain CY04T, was isolated from a sediment sample collected from the Yellow Sea. CY04T exhibited the highest 16S rRNA gene sequence similarity of 98.7 % to Zongyanglinia huanghaiensis CY05T, followed by the similarities of 98.6 %, 98.0 and 98.0 % to Zongyanglinia marina DSW4-44T, Parasedimentitalea marina W43T and Parasedimentitalea psychrophila QS115T respectively. Phylogenetic analysis based on 16S rRNA gene and phylogenomic analysis based on genome sequences revealed that CY04T formed a robust cluster with Z. huanghaiensis CY05T, Z. marina DSW4-44T, P. marina W43T and P. psychrophila QS115T. Calculated digital DNA-DNA hybridisation and average nucleotide identity values between CY04T and its closely related species were 22.2-23.7 % and 79.0-81.2 % respectively. Cells of CY04T were strictly aerobic, non-motile and positive for catalase, oxidase and denitrification. CY04T harboured a set of genes encoding the enzymes involved in denitrification. Growth occurred at 10-30 °C (optimum, 20 °C), at pH 6.5-9.5 (optimum, pH 8.0) and with 1-6 % (w/v) (optimum, 2.5 %,) NaCl. The major component of the fatty acids was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The isoprenoid quinone was Q-10. Results of the phenotypic, chemotaxonomic and molecular study indicate that strain CY04T represents a novel species of the genus Parasedimentitalea, for which the name Parasedimentitalea denitrificans sp. nov. is proposed. The type strain is CY04T (=MCCC 1K08635T=KCTC 62199T). It is also proposed that Zongyanglinia huanghaiensis and Zongyanglinia marina should be reclassified as Parasedimentitalea huanghaiensis comb. nov. and Parasedimentitalea maritima nom. nov. An emended description of the genus Parasedimentitalea is also proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Denitrification , Fatty Acids , Geologic Sediments , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Seawater , Sequence Analysis, DNA , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Geologic Sediments/microbiology , China , Seawater/microbiology , Ubiquinone
7.
Article in English | MEDLINE | ID: mdl-38743058

ABSTRACT

Two strictly aerobic and rod-shaped bacteria, labelled as DB1703T and DB2414ST, were obtained from an automobile air conditioning system. Strain DB1703T was Gram-stain-negative, while strain DB2414ST was Gram-stain-positive. Both strains were catalase-positive and oxidase-negative. Strains DB1703T and DB2414ST were able to grow at 18-42 °C. Strain DB1703T grew within a NaCl range of 0-3 % and a pH range of 6.0-8.0; while strain DB2414ST grew at 0-1 % and pH 6.5-8.5. The phylogenetic and 16S rRNA gene sequence analysis indicated that strains DB1703T and DB2414ST belonged to the genera Enterovirga and Knoellia, respectively. Strain DB1703T showed the closest phylogenetic similarity to Enterovirga rhinocerotis YIM 100770T (94.8 %), whereas strain DB2414ST was most closely related to Knoellia remsis ATCC BAA-1496T (97.7 %). The genome sizes of strains DB1703T and DB2414ST were 4 652 148 and 4 282 418 bp, respectively, with DNA G+C contents of 68.8 and 70.5 mol%, respectively. Chemotaxonomic data showed Q-10 as the sole ubiquinone in DB1703T and ML-8 (H4) in DB2414ST. The predominant cellular fatty acid in DB1703T was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), whereas iso-C16 : 0, C17 : 1 ω8c, and iso-C15 : 0 were dominant in DB2414ST. Overall, the polyphasic taxonomic comparisons showed that strains DB1703T and DB2414ST were distinct from their closest taxa and represent novel species within the genera Enterovirga and Knoellia, respectively. Accordingly, we propose the names Enterovirga aerilata sp. nov., with the type strain DB1703T (=KCTC 72724T=NBRC 114759T), and Knoellia koreensis sp. nov., with the type strain DB2414ST (=KCTC 49355T=NBRC 114620T).


Subject(s)
Air Conditioning , Automobiles , Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Ubiquinone , Fatty Acids/analysis , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Republic of Korea
8.
Article in English | MEDLINE | ID: mdl-38747693

ABSTRACT

The use of algae as feedstock for industrial purposes, such as in bioethanol production, is desirable. During a search for new agarolytic marine bacteria, a novel Gram-stain-negative, strictly aerobic, and agarolytic bacterium, designated as TS8T, was isolated from algae in the harbour of the island of Susak, Croatia. The cells were rod-shaped and motile. The G+C content of the sequenced genome was 38.6 mol%. Growth was observed at 11-37 °C, with 0.5-13 % (w/v) NaCl, and at pH 6.0-9.0. The main fatty acids were summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), and C16 : 0. The main respiratory quinone was ubiquinone-8. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Analysis of 16S rRNA gene sequences indicated that the newly isolated strain belongs to the genus Catenovulum. Based on 16S rRNA gene sequence data, strain TS8T is closely related to Catenovulum sediminis D2T (95.7 %), Catenovulum agarivorans YM01T (95.0 %), and Catenovulum maritimum Q1T (93.2 %). Digital DNA-DNA hybridization values between TS8T and the other Catenovulum strains were below 25 %. Based on genotypic, phenotypic, and phylogenetic data, strain TS8T represents a new species of the genus Catenovulum, for which the name Catenovulum adriaticum sp. nov. is proposed. The type strain is TS8T (=DSM 114830T=NCIMB 15451T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Ubiquinone , RNA, Ribosomal, 16S/genetics , Fatty Acids/analysis , Fatty Acids/chemistry , Croatia , DNA, Bacterial/genetics , Phospholipids/chemistry , Phospholipids/analysis , Nucleic Acid Hybridization , Phosphatidylethanolamines
9.
Int J Immunopathol Pharmacol ; 38: 3946320241250286, 2024.
Article in English | MEDLINE | ID: mdl-38764158

ABSTRACT

Background: Aluminum phosphide (AlP) poisoning is prevalent in numerous countries, resulting in high mortality rates. Phosphine gas, the primary agent responsible for AlP poisoning, exerts detrimental effects on various organs, notably the heart, liver and kidneys. Numerous studies have documented the advantageous impact of Coenzyme Q10 (CoQ10) in mitigating hepatic injuries. The objective of this investigation is to explore the potential protective efficacy of CoQ10 against hepatic toxicity arising from AlP poisoning. Method: The study encompassed distinct groups receiving almond oil, normal saline, exclusive CoQ10 (at a dosage of 100 mg/kg), AlP at 12 mg/kg; LD50 (lethal dose for 50%), and four groups subjected to AlP along with CoQ10 administration (post-AlP gavage). CoQ10 was administered at 10, 50, and 100 mg/kg doses via Intraparietal (ip) injections. After 24 h, liver tissue specimens were scrutinized for mitochondrial complex activities, oxidative stress parameters, and apoptosis as well as biomarkers such as aspartate transaminase (AST) and alanine transaminase (ALT). Results: AlP induced a significant decrease in the activity of mitochondrial complexes I and IV, as well as a reduction in catalase activity, Ferric Reducing Antioxidant Power (FRAP), and Thiol levels. Additionally, AlP significantly elevated oxidative stress levels, indicated by elevated reactive oxygen species (ROS) production, and resulted in the increment of hepatic biomarkers such as AST and ALT. Administration of CoQ10 led to a substantial improvement in the aforementioned biochemical markers. Furthermore, phosphine exposure resulted in a significant reduction in viable hepatocytes and an increase in apoptosis. Co-treatment with CoQ10 exhibited a dose-dependent reversal of these observed alterations. Conclusion: CoQ10 preserved mitochondrial function, consequently mitigating oxidative damage. This preventive action impeded the progression of heart cells toward apoptosis.


Subject(s)
Chemical and Drug Induced Liver Injury , Liver , Oxidative Stress , Phosphines , Ubiquinone , Phosphines/poisoning , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquinone/therapeutic use , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/etiology , Animals , Oxidative Stress/drug effects , Male , Liver/drug effects , Liver/metabolism , Liver/pathology , Apoptosis/drug effects , Antioxidants/pharmacology , Antioxidants/therapeutic use , Rats , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/metabolism , Aluminum Compounds/toxicity , Alanine Transaminase/blood , Alanine Transaminase/metabolism , Reactive Oxygen Species/metabolism , Rats, Wistar
11.
Article in English | MEDLINE | ID: mdl-38787363

ABSTRACT

A Gram-negative, rod-shaped, non-motile and strictly aerobic strain, designated NBU2979T, was isolated from a coastal mudflat located on Meishan Island in the East China Sea. Strain NBU2979T grew optimally at 32 °C, with 2.0 % NaCl (w/v) and at pH 7.0-7.5. The predominant fatty acid (>10 %) was iso-C15 : 0. The major polar lipids included phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidyldimethylethanolamine, phosphatidylcholine, an unidentified glycolipid, two unidentified aminophospholipids, an unidentified phospholipid and an unidentified lipid. The only respiratory quinone was ubiquinone-8. Comparative analysis of 16S rRNA gene sequences showed that strain NBU2979T exhibited highest similarity to Marinicella sediminis F2T (98.0 %), Marinicella marina S1101T (97.5 %), Marinicella litoralis KMM 3900T (96.6 %), Marinicella rhabdoformis 3539T (95.5 %), Marinicella pacifica sw153T (95.2 %) and Marinicella gelatinilytica S6413T (94.9 %). Phylogenetic analyses indicated that strain NBU2979T clustered with the genus Marinicella and was closely related to strain M. sediminis F2T. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU2979T and related species of genus Marinicella were well below the threshold limit for prokaryotic species delineation. The DNA G+C content of strain NBU2979T was 51.6 mol%. Based on its phenotypic, chemotaxonomic and genotypic data, strain NBU2979T (=KCTC 82911T=MCCC 1K06402T) is considered to be a representative of a novel species in the genus Marinicella, for which the name Marinicella meishanensis sp. nov. is proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Nucleic Acid Hybridization , Phospholipids , Phylogeny , RNA, Ribosomal, 16S , Seawater , Sequence Analysis, DNA , Ubiquinone , China , RNA, Ribosomal, 16S/genetics , Fatty Acids/chemistry , Geologic Sediments/microbiology , DNA, Bacterial/genetics , Seawater/microbiology , Ubiquinone/analogs & derivatives , Phospholipids/chemistry , Islands , Molecular Sequence Data
12.
Braz J Med Biol Res ; 57: e13474, 2024.
Article in English | MEDLINE | ID: mdl-38716985

ABSTRACT

Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.


Subject(s)
Autophagy , Osteoclasts , Osteogenesis , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RANK Ligand , TOR Serine-Threonine Kinases , Ubiquinone , Animals , Mice , Autophagy/drug effects , Cell Differentiation/drug effects , Cell Survival/drug effects , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Osteoclasts/drug effects , Osteogenesis/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RANK Ligand/metabolism , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology
13.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732133

ABSTRACT

Treating female canine mammary gland tumors is crucial owing to their propensity for rapid progression and metastasis, significantly impacting the overall health and well-being of dogs. Mitoquinone (MitoQ), an antioxidant, has shown promise in inhibiting the migration, invasion, and clonogenicity of human breast cancer cells. Thus, we investigated MitoQ's potential anticancer properties against canine mammary gland tumor cells, CMT-U27 and CF41.Mg. MitoQ markedly suppressed the proliferation and migration of both CMT-U27 and CF41.Mg cells and induced apoptotic cell death in a dose-dependent manner. Furthermore, treatment with MitoQ led to increased levels of pro-apoptotic proteins, including cleaved-caspase3, BAX, and phospho-p53. Cell cycle analysis revealed that MitoQ hindered cell progression in the G1 and S phases in CMT-U27 and CF41.Mg cells. These findings were supported using western blot analysis, demonstrating elevated levels of cleaved caspase-3, a hallmark of apoptosis, and decreased expression of cyclin-dependent kinase (CDK) 2 and cyclin D4, pivotal regulators of the cell cycle. In conclusion, MitoQ exhibits in vitro antitumor effects by inducing apoptosis and arresting the cell cycle in canine mammary gland tumors, suggesting its potential as a preventive or therapeutic agent against canine mammary cancer.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Cycle Checkpoints , Cell Proliferation , Mammary Neoplasms, Animal , Organophosphorus Compounds , Ubiquinone , Animals , Dogs , Apoptosis/drug effects , Mammary Neoplasms, Animal/drug therapy , Mammary Neoplasms, Animal/pathology , Mammary Neoplasms, Animal/metabolism , Female , Cell Line, Tumor , Cell Cycle Checkpoints/drug effects , Antineoplastic Agents/pharmacology , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Organophosphorus Compounds/pharmacology , Cell Proliferation/drug effects , Cell Movement/drug effects
14.
Anim Reprod Sci ; 265: 107487, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723402

ABSTRACT

Cryopreservation of small ruminant's semen is an effective strategy for distributing spermatozoa for reproductive programs, but this process decreases the fertility potential of post-thawed spermatozoa. The aim of this research was to assess the effect of different concentrations of CoQ10 in soybean lecithin (SL)-based extender on buck semen quality during cryopreservation process. Semen samples were collected from five bucks, twice a week, then diluted in the SL-based extender containing different concentrations of CoQ10 as follows: extender containing 0 µM (control, Q0), 0.1 µM (Q0.1), 1 µM (Q1), 10 µM (Q10) and 100 µM (Q100) CoQ10. Motion characteristics, membrane functionality, abnormal morphology, mitochondrial activity, acrosome integrity, viability, apoptotic-like changes, lipid peroxidation, DNA fragmentation and ROS concentration were evaluated after freeze-thawing process. The Q10 resulted in greater (P≤0.05) total motility, progressive motility, average path velocity, membrane integrity, mitochondrial activity, acrosome integrity and viability compared to the other groups. Furthermore, supplementation of freezing extender with 10 µM of CoQ10 presented lower (P≤0.05) apoptotic-like changes, lipid peroxidation, DNA fragmentation and ROS concentration compared to the other groups. Regarding to the protective effect of CoQ10 supplement during cryopreservation process, it could be explored as a potent antioxidant for cryopreservation of buck semen as it preserved the post-thawed buck sperm quality.


Subject(s)
Cryopreservation , Cryoprotective Agents , Goats , Semen Analysis , Semen Preservation , Spermatozoa , Ubiquinone , Ubiquinone/pharmacology , Ubiquinone/analogs & derivatives , Male , Cryopreservation/veterinary , Cryopreservation/methods , Semen Preservation/veterinary , Semen Preservation/methods , Animals , Semen Analysis/veterinary , Cryoprotective Agents/pharmacology , Spermatozoa/drug effects , Spermatozoa/physiology , Goats/physiology , Sperm Motility/drug effects , Glycine max/chemistry
15.
Nat Commun ; 15(1): 4277, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769288

ABSTRACT

Elevated intracellular sodium Nai adversely affects mitochondrial metabolism and is a common feature of heart failure. The reversibility of acute Na induced metabolic changes is evaluated in Langendorff perfused rat hearts using the Na/K ATPase inhibitor ouabain and the myosin-uncoupler para-aminoblebbistatin to maintain constant energetic demand. Elevated Nai decreases Gibb's free energy of ATP hydrolysis, increases the TCA cycle intermediates succinate and fumarate, decreases ETC activity at Complexes I, II and III, and causes a redox shift of CoQ to CoQH2, which are all reversed on lowering Nai to baseline levels. Pseudo hypoxia and stabilization of HIF-1α is observed despite normal tissue oxygenation. Inhibition of mitochondrial Na/Ca-exchange with CGP-37517 or treatment with the mitochondrial ROS scavenger MitoQ prevents the metabolic alterations during Nai elevation. Elevated Nai plays a reversible role in the metabolic and functional changes and is a novel therapeutic target to correct metabolic dysfunction in heart failure.


Subject(s)
Mitochondria, Heart , Sodium , Animals , Rats , Mitochondria, Heart/metabolism , Mitochondria, Heart/drug effects , Sodium/metabolism , Male , Myocardium/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Heart Failure/metabolism , Heart Failure/drug therapy , Adenosine Triphosphate/metabolism , Citric Acid Cycle/drug effects , Rats, Sprague-Dawley , Organophosphorus Compounds/pharmacology , Organophosphorus Compounds/metabolism , Sodium-Calcium Exchanger/metabolism , Ubiquinone/metabolism , Ubiquinone/analogs & derivatives , Sodium-Potassium-Exchanging ATPase/metabolism , Oxidation-Reduction , Succinic Acid/metabolism
16.
Life Sci ; 348: 122688, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38710284

ABSTRACT

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1ß, MCP-1, JNK1, and TGF-ß in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.


Subject(s)
Cadmium , Cardiotoxicity , Inflammasomes , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 Protein , Oxidative Stress , Ubiquinone , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Mice , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Oxidative Stress/drug effects , Cardiotoxicity/drug therapy , Cardiotoxicity/metabolism , Cardiotoxicity/prevention & control , NF-kappa B/metabolism , Inflammasomes/metabolism , Inflammasomes/drug effects , Male , Cadmium/toxicity , Down-Regulation/drug effects , Antioxidants/pharmacology
17.
Article in English | MEDLINE | ID: mdl-38805027

ABSTRACT

Strain S30A2T, isolated from the acid mine drainage sediment of Mengzi Copper Mine, Yunnan, is proposed to represent a novel species of the sulphur-oxidizing genus Acidithiobacillus. Cells were Gram-stain-negative, non-endospore forming, highly motile with one or two monopolar flagella and rod-shaped. The strain was mesophilic, growing at 30-50 °C (optimum, 38 °C), acidophilic, growing at pH 2.0-4.5 (optimum, pH 2.5), and tolerant of 0-4 % (w/v; 684 mol l-1) NaCl. The 16S rRNA gene-based sequence analysis showed that strain S30A2T belongs to the genus Acidithiobacillus and shows the largest similarity of 96.6 % to the type strain Acidithiobacillus caldus KUT. The genomic DNA G+C content of strain S30A2T was 59.25 mol%. The average nucleotide identity ANIb and ANIm values between strain S30A2T and A. caldus KUT were 70.95 and 89.78 %, respectively and the digital DNA-DNA hybridization value was 24.9 %. Strain S30A2T was strictly aerobic and could utilize elementary sulphur and tetrathionate to support chemolithotrophic growth. The major cellular fatty acid of S30A2T was C19 : 1ω7c. The respiratory quinones were ubiquinone-8 and ubiquinone-7. Based upon its phylogenetic, genetic, phenotypic, physiologic and chemotaxonomic characteristics, strain S30A2T is considered to represent a novel species of the genus Acidithiobacillus, for which the name Acidithiobacillus acidisediminis sp. nov. is proposed. The type strain is S30A2T (=CGMCC 1.17059T=KCTC 72580T).


Subject(s)
Acidithiobacillus , Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Geologic Sediments , Mining , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Sulfur , RNA, Ribosomal, 16S/genetics , Sulfur/metabolism , DNA, Bacterial/genetics , Fatty Acids/analysis , Geologic Sediments/microbiology , Acidithiobacillus/classification , Acidithiobacillus/genetics , Acidithiobacillus/isolation & purification , China , Oxidation-Reduction , Chemoautotrophic Growth , Ubiquinone , Copper/metabolism
18.
JBRA Assist Reprod ; 28(2): 276-283, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38775323

ABSTRACT

OBJECTIVE: Cryopreservation has some adverse effects on embryos including cell metabolism reduction, mitochondria and plasma membrane damage, excess production of 'Reactive Oxygen Species' and damage to DNA. In the present study. In this study we assessed the effect of coenzyme Q10 as an exogenous antioxidant on mouse embryos following cryopreservation. METHODS: We collected mice embryos at the morula stage from uterine horns on the third day of gestation. The morulae were divided into 9 groups (1 control, 2 vehicles and 6 experimental), then vitrified. The culture and/or vitrification media of the experimental groups were supplemented by 10 or 30 µM of CoQ10. After one week, the embryos were warmed and then cultured. After 48 hours of embryo culture, the blastocyst rate, total cell number, viability; and after 72 hours of embryo culture, we assessed the hatching rate. RESULTS: Blastocyst rate and hatching rate were significantly reduced in the groups containing 30 µM CoQ10 supplemented culture media compared to other groups (p<0.05). The hatching rate in the groups containing 10 µM CoQ10 supplemented in both culture and vitrification media was significantly higher than in the other groups (p<0.05). In groups containing 10 µM CoQ10 supplemented culture media, the viability was higher than that in the other groups (p<0.05). CONCLUSIONS: It seems that CoQ10 in a dose-dependent manner is able to improve hatching rate and viability following cryopreservation through its antioxidant and anti-apoptotic properties, and through the production of ATP.


Subject(s)
Cryopreservation , Ubiquinone , Animals , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Mice , Female , Embryo Culture Techniques , Embryonic Development/drug effects , Blastocyst/drug effects , Vitrification/drug effects , Embryo, Mammalian/drug effects , Antioxidants/pharmacology , Pregnancy
19.
BMC Med ; 22(1): 191, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714999

ABSTRACT

BACKGROUND: Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL). METHODS: Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses. RESULTS: In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group. CONCLUSIONS: Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.


Subject(s)
Cardiovascular Diseases , Dietary Supplements , Quality of Life , Selenium , Thyroid Hormones , Ubiquinone , Humans , Ubiquinone/analogs & derivatives , Ubiquinone/administration & dosage , Ubiquinone/blood , Selenium/administration & dosage , Selenium/blood , Male , Aged , Female , Thyroid Hormones/blood , Double-Blind Method , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Sweden/epidemiology , Aged, 80 and over , Middle Aged , Placebos/administration & dosage
20.
Cell Rep ; 43(5): 114148, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38697100

ABSTRACT

Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ10. Poor outcomes result from low absorption and bioavailability of CoQ10 and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ10 supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency.


Subject(s)
Disease Models, Animal , Mitochondrial Diseases , Parabens , Ubiquinone , Animals , Mitochondrial Diseases/drug therapy , Mitochondrial Diseases/pathology , Mitochondrial Diseases/metabolism , Parabens/pharmacology , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Ubiquinone/metabolism , Ubiquinone/deficiency , Mice , Mitochondria/metabolism , Mitochondria/drug effects , Humans , Fibroblasts/metabolism , Fibroblasts/drug effects , Mice, Inbred C57BL , Muscle Weakness/drug therapy , Muscle Weakness/metabolism , Muscle Weakness/pathology , Ataxia/drug therapy , Ataxia/pathology , Ataxia/metabolism
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