Pub Date : 2025-01-30DOI: 10.1038/s41684-024-01504-1
Hong-Wei Su, Cai-Wei Qiu
This Review evaluates various mouse and rat models of chronic kidney disease (CKD) that result from repeated low-dose cisplatin (RLDC) treatment while also discussing ethical considerations on the topic. Cisplatin can cause nephrotoxicity, and high doses of cisplatin can cause acute kidney injury. The RLDC regimen has been used in the treatment of solid organ cancers and has shown efficacy in reducing the occurrence of acute kidney injury in patients. However, prolonged treatments may lead to CKD. Mouse and rat models that effectively replicate the pathological features of CKD are invaluable for studying the mechanisms of the disease and exploring potential therapeutic interventions. Whereas administration of a single higher dose in some RLDC models may lead to higher mortality rates, a single lower dose may not replicate the fibrotic characteristics of CKD. Here we gathered information on mouse and rat models of RLDC-induced CKD and analyzed the impact of different variables, such as animal age, cisplatin dosage and administration frequency, on success rates, mortality rate and weight loss. Among the different models, weekly intraperitoneal administration of 8 mg/kg or 9 mg/kg of cisplatin for a total of 4 weeks in 12-week-old male C57BL/6 mice showed the most similar clinical characteristics of CKD while adhering to ethical requirements. In this Review, we suggest the best timings for both drug intervention and observation based on the biological traits of the model. Furthermore, given the limited research available on RLDC-induced CKD rat models, it is urgent to focus on developing RLDC methods that can induce detailed characteristics of CKD in rats. This Review assesses murine models of chronic kidney disease caused by low-dose cisplatin treatment, discussing ethical considerations as well as variables’ impact on success, mortality and weight loss. The authors also suggest optimal intervention timings.
{"title":"A comparative review of murine models of repeated low-dose cisplatin-induced chronic kidney disease","authors":"Hong-Wei Su, Cai-Wei Qiu","doi":"10.1038/s41684-024-01504-1","DOIUrl":"10.1038/s41684-024-01504-1","url":null,"abstract":"This Review evaluates various mouse and rat models of chronic kidney disease (CKD) that result from repeated low-dose cisplatin (RLDC) treatment while also discussing ethical considerations on the topic. Cisplatin can cause nephrotoxicity, and high doses of cisplatin can cause acute kidney injury. The RLDC regimen has been used in the treatment of solid organ cancers and has shown efficacy in reducing the occurrence of acute kidney injury in patients. However, prolonged treatments may lead to CKD. Mouse and rat models that effectively replicate the pathological features of CKD are invaluable for studying the mechanisms of the disease and exploring potential therapeutic interventions. Whereas administration of a single higher dose in some RLDC models may lead to higher mortality rates, a single lower dose may not replicate the fibrotic characteristics of CKD. Here we gathered information on mouse and rat models of RLDC-induced CKD and analyzed the impact of different variables, such as animal age, cisplatin dosage and administration frequency, on success rates, mortality rate and weight loss. Among the different models, weekly intraperitoneal administration of 8 mg/kg or 9 mg/kg of cisplatin for a total of 4 weeks in 12-week-old male C57BL/6 mice showed the most similar clinical characteristics of CKD while adhering to ethical requirements. In this Review, we suggest the best timings for both drug intervention and observation based on the biological traits of the model. Furthermore, given the limited research available on RLDC-induced CKD rat models, it is urgent to focus on developing RLDC methods that can induce detailed characteristics of CKD in rats. This Review assesses murine models of chronic kidney disease caused by low-dose cisplatin treatment, discussing ethical considerations as well as variables’ impact on success, mortality and weight loss. The authors also suggest optimal intervention timings.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 2","pages":"42-49"},"PeriodicalIF":5.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-27DOI: 10.1038/s41684-024-01505-0
David-Samuel Burkhardt, Claire Leyden, Carina Thomas, Christian Brysch, Florian Alexander Dehmelt, Aristides B. Arrenberg
Two methods dominate the way that zebrafish larvae are euthanized after experimental procedures: anesthetic overdose and rapid cooling. Although MS-222 is easy to apply, this anesthetic takes about a minute to act and fish show aversive reactions and interindividual differences, limiting its reliability. Rapid cooling kills larvae after several hours and is not listed as an approved method in the relevant European Union directive. Electrical stunning is a promising alternative euthanasia method for zebrafish but has not yet been fully established. Here we characterize both behavioral and neurophysiological effects of electrical stunning in 4-day-old zebrafish larvae. We identified the electric field characteristics and stimulus duration (50 V/cm alternating current for 32 s) that reliably euthanizes free-swimming larvae and agarose-embedded larvae with an easy-to-implement protocol. Behavioral analysis and calcium neurophysiology show that larvae lose consciousness and stop responding to touch and visual stimuli very quickly (<1 s). Electrically stunned larvae no longer show coordinated brain activity. Their brains instead undergo a series of concerted whole-brain calcium waves over the course of many minutes before the cessation of all brain signals. Consistent with the need to implement the 3R at all stages of animal experimentation, the rapid and reliable euthanasia achieved by electrical stunning has potential for refinement of the welfare of more than 5 million zebrafish used annually in biomedical research worldwide. This study explores the use of electrical stunning as a viable alternative to anesthetic overdose and rapid cooling for euthanizing zebrafish larvae, potentially improving the welfare of over 5 million zebrafish in biomedical research.
{"title":"Behavioral and neurophysiological effects of electrical stunning on zebrafish larvae","authors":"David-Samuel Burkhardt, Claire Leyden, Carina Thomas, Christian Brysch, Florian Alexander Dehmelt, Aristides B. Arrenberg","doi":"10.1038/s41684-024-01505-0","DOIUrl":"10.1038/s41684-024-01505-0","url":null,"abstract":"Two methods dominate the way that zebrafish larvae are euthanized after experimental procedures: anesthetic overdose and rapid cooling. Although MS-222 is easy to apply, this anesthetic takes about a minute to act and fish show aversive reactions and interindividual differences, limiting its reliability. Rapid cooling kills larvae after several hours and is not listed as an approved method in the relevant European Union directive. Electrical stunning is a promising alternative euthanasia method for zebrafish but has not yet been fully established. Here we characterize both behavioral and neurophysiological effects of electrical stunning in 4-day-old zebrafish larvae. We identified the electric field characteristics and stimulus duration (50 V/cm alternating current for 32 s) that reliably euthanizes free-swimming larvae and agarose-embedded larvae with an easy-to-implement protocol. Behavioral analysis and calcium neurophysiology show that larvae lose consciousness and stop responding to touch and visual stimuli very quickly (<1 s). Electrically stunned larvae no longer show coordinated brain activity. Their brains instead undergo a series of concerted whole-brain calcium waves over the course of many minutes before the cessation of all brain signals. Consistent with the need to implement the 3R at all stages of animal experimentation, the rapid and reliable euthanasia achieved by electrical stunning has potential for refinement of the welfare of more than 5 million zebrafish used annually in biomedical research worldwide. This study explores the use of electrical stunning as a viable alternative to anesthetic overdose and rapid cooling for euthanizing zebrafish larvae, potentially improving the welfare of over 5 million zebrafish in biomedical research.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 2","pages":"50-58"},"PeriodicalIF":5.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01505-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1038/s41684-024-01495-z
Alexandra Le Bras
{"title":"Glucokinase regulation in zebrafish","authors":"Alexandra Le Bras","doi":"10.1038/s41684-024-01495-z","DOIUrl":"10.1038/s41684-024-01495-z","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 1","pages":"1-1"},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1038/s41684-024-01503-2
Jorge Ferreira
{"title":"Rabbit model of age-related macular degeneration","authors":"Jorge Ferreira","doi":"10.1038/s41684-024-01503-2","DOIUrl":"10.1038/s41684-024-01503-2","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 1","pages":"6-6"},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01503-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-03DOI: 10.1038/s41684-024-01494-0
Alexandra Le Bras
{"title":"Mito-NAD(P)H age clocks in C.elegans","authors":"Alexandra Le Bras","doi":"10.1038/s41684-024-01494-0","DOIUrl":"10.1038/s41684-024-01494-0","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 1","pages":"1-1"},"PeriodicalIF":5.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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