Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo
Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes a...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320723000052 |
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| author | Jiao Mo Hongfei Si Siyang Liu Qingyuan Zeng Minghao Cai Zhendi Liu Jiyu Zhang Jingjing Fang Jili Zhang |
| author_facet | Jiao Mo Hongfei Si Siyang Liu Qingyuan Zeng Minghao Cai Zhendi Liu Jiyu Zhang Jingjing Fang Jili Zhang |
| author_sort | Jiao Mo |
| collection | DOAJ |
| description | Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The in vitro effects of HQNO were determined by plaque assay and qPCR assay. To determine the in vivo effect of HQNO, pharmacokinetic experiments and in vivo infection assays were performed in mice. The changes in tachyzoites after HQNO exposure were examined by transmission electron microscopy (TEM), MitoTracker Red CMXRos staining, ROS detection and ATP detection. HQNO inhibited T. gondii invasion and proliferation with an EC50 of 0.995 μM. Pharmacokinetic experiments showed that the Cmax of HQNO (20 mg/kg·bw) was 3560 ± 1601 ng/mL (13.73 μM) in healthy BALB/c mouse plasma with no toxicity in vivo. Moreover, HQNO induced a significant decrease in the parasite burden load of T. gondii in mouse peritoneum. TEM revealed alterations in the mitochondria of T. gondii. Further assays verified that HQNO also decreased the mitochondrial membrane potential (ΔΨm) and ATP levels and enhanced the level of reactive oxygen species (ROS) in T. gondii. Hence, HQNO exerted anti-T. gondii activity, which may be related to the damage to the mitochondrial electron transport chain (ETC). |
| first_indexed | 2024-04-09T20:20:28Z |
| format | Article |
| id | doaj.art-0523874fcd5745cc9ed0b5a5c9ba6b84 |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-04-09T20:20:28Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-0523874fcd5745cc9ed0b5a5c9ba6b842023-03-31T05:53:20ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072023-04-01217480Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivoJiao Mo0Hongfei Si1Siyang Liu2Qingyuan Zeng3Minghao Cai4Zhendi Liu5Jiyu Zhang6Jingjing Fang7Jili Zhang8School of Medicine, Ningbo University, Ningbo, ChinaCollege of Pharmacy, Jinan University, Guangzhou, ChinaSchool of Medicine, Ningbo University, Ningbo, ChinaSchool of Medicine, Ningbo University, Ningbo, ChinaSchool of Medicine, Ningbo University, Ningbo, ChinaSchool of Medicine, Ningbo University, Ningbo, ChinaLanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Science, ChinaIntensive Care Unit, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, ChinaSchool of Medicine, Ningbo University, Ningbo, China; Intensive Care Unit, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China; Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Science, China; Corresponding author. School of Medicine, Ningbo University, Ningbo, Zhejiang, 315211, China.Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The in vitro effects of HQNO were determined by plaque assay and qPCR assay. To determine the in vivo effect of HQNO, pharmacokinetic experiments and in vivo infection assays were performed in mice. The changes in tachyzoites after HQNO exposure were examined by transmission electron microscopy (TEM), MitoTracker Red CMXRos staining, ROS detection and ATP detection. HQNO inhibited T. gondii invasion and proliferation with an EC50 of 0.995 μM. Pharmacokinetic experiments showed that the Cmax of HQNO (20 mg/kg·bw) was 3560 ± 1601 ng/mL (13.73 μM) in healthy BALB/c mouse plasma with no toxicity in vivo. Moreover, HQNO induced a significant decrease in the parasite burden load of T. gondii in mouse peritoneum. TEM revealed alterations in the mitochondria of T. gondii. Further assays verified that HQNO also decreased the mitochondrial membrane potential (ΔΨm) and ATP levels and enhanced the level of reactive oxygen species (ROS) in T. gondii. Hence, HQNO exerted anti-T. gondii activity, which may be related to the damage to the mitochondrial electron transport chain (ETC).http://www.sciencedirect.com/science/article/pii/S2211320723000052HQNOToxoplasma gondiiInvasionProliferationPharmacokineticsIn vivo |
| spellingShingle | Jiao Mo Hongfei Si Siyang Liu Qingyuan Zeng Minghao Cai Zhendi Liu Jiyu Zhang Jingjing Fang Jili Zhang Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo International Journal for Parasitology: Drugs and Drug Resistance HQNO Toxoplasma gondii Invasion Proliferation Pharmacokinetics In vivo |
| title | Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo |
| title_full | Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo |
| title_fullStr | Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo |
| title_full_unstemmed | Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo |
| title_short | Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo |
| title_sort | effect of the pseudomonas metabolites hqno on the toxoplasma gondii rh strain in vitro and in vivo |
| topic | HQNO Toxoplasma gondii Invasion Proliferation Pharmacokinetics In vivo |
| url | http://www.sciencedirect.com/science/article/pii/S2211320723000052 |
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