Marjan Diricx - Academia.edu (original) (raw)

Papers by Marjan Diricx

Clinical use of doxorubicin (Dox) is limited by cumulative myeloand cardiotoxicity. This research... more Clinical use of doxorubicin (Dox) is limited by cumulative myeloand cardiotoxicity. This research focuses on the detailed characterization of PhAc-ALGP-Dox, a targeted tetrapeptide prodrug with a unique dual-step activation mechanism, designed to circumvent Dox-related toxicities and is ready for upcoming clinical investigation. Coupling Dox to a phosphonoacetyl (PhAc)-capped tetrapeptide forms the cell-impermeable, inactive compound, PhAc-ALGP-Dox. After extracellular cleavage by tumor-enriched thimet oligopeptidase-1 (THOP1), a cell-permeable but still biologically inactive dipeptide-conjugate is formed (GP-Dox), which is further processed intracellularly to Dox by fibroblast activation proteinalpha (FAPa) and/or dipeptidyl peptidase-4 (DPP4). In vitro, PhAc-ALGP-Dox is effective in various 2D-and 3D-cancer models, while showing improved safety toward normal epithelium, hematopoietic progenitors, and cardiomyocytes. In vivo, these results translate into a 10-fold higher tolerability and 5-fold greater retention of Dox in the tumor microenvironment compared with the parental drug. PhAc-ALGP-Dox demonstrates 63% to 96% tumor growth inhibition in preclinical models, an 8-fold improvement in efficacy in patient-derived xenograft (PDX) models, and reduced metastatic burden in a murine model of experimental lung metastasis, improving survival by 30%. The current findings highlight the potential clinical benefit of PhAc-ALGP-Dox, a targeted drugconjugate with broad applicability, favorable tissue biodistribution, significantly improved tolerability, and tumor growth inhibition at primary and metastatic sites in numerous solid tumor models.

Clinical use of doxorubicin (Dox) is limited by cumulative myelo- and cardiotoxicity. This resear... more Clinical use of doxorubicin (Dox) is limited by cumulative myelo- and cardiotoxicity. This research focuses on the detailed characterization of PhAc-ALGP-Dox, a targeted tetrapeptide prodrug with a unique dual-step activation mechanism, designed to circumvent Dox-related toxicities and is ready for upcoming clinical investigation. Coupling Dox to a phosphonoacetyl (PhAc)-capped tetrapeptide forms the cell-impermeable, inactive compound, PhAc-ALGP-Dox. After extracellular cleavage by tumor-enriched thimet oligopeptidase-1 (THOP1), a cell-permeable but still biologically inactive dipeptide-conjugate is formed (GP-Dox), which is further processed intracellularly to Dox by fibroblast activation protein-alpha (FAPα) and/or dipeptidyl peptidase-4 (DPP4). In vitro, PhAc-ALGP-Dox is effective in various 2D- and 3D-cancer models, while showing improved safety toward normal epithelium, hematopoietic progenitors, and cardiomyocytes. In vivo, these results translate into a 10-fold higher tolera...

Investigative ophthalmology & visual science, Mar 1, 2017

The purpose of this study was to evaluate the dispersion of intravitreally injected solutions and... more The purpose of this study was to evaluate the dispersion of intravitreally injected solutions and investigate the influence of varying injection techniques. This was a prospective study using enucleated porcine eyes and ultra-high-resolution computed tomography (UHRCT) scanning to visualize iomeprol intravitreal dispersion. Sixty eyes were divided over 12 different groups according to the injection procedure: fast (2 seconds) or slow (10 seconds) injection speed and needle tip location (6- and 12-mm needle shaft insertion or premacular tip placement verified by indirect ophthalmoscopy). For each of these combinations, eyes were either injected with the combination of V20I (which is an analogue of ocriplasmin) and iomeprol or iomeprol alone. Distance to the macula and volume measurements were performed at 1, 2, 3, and 5 hours after injection. The measured contrast bolus volume increases slowly over time to an average of 0.70 (P = 0.03), 1.04 (P = 0.006), and 0.79 (P = 0.0001) cm3 5 h...

Aquatic Toxicology, Jun 1, 2012

Due to eutrophication, high environmental ammonia (HEA) has become a frequent problem in aquatic ... more Due to eutrophication, high environmental ammonia (HEA) has become a frequent problem in aquatic environments, especially in agricultural or densely populated areas. During certain periods, e.g. winter, feed deprivation may occur simultaneously in natural waters. Additionally, under such stressful circumstances, fish may be enforced to swim at a high speed in order to catch prey, avoid predators and so on. Consequently, fish need to cope with all these stressors by altering physiological processes which in turn are controlled by genes expression. Therefore, in the present study, ammonia toxicity was tested in function of nutrient status (fed versus starved) and swimming performance activity (routine versus exhaustive). Goldfish, a relatively tolerant cyprinid, were exposed to HEA (1 mg/L; Flemish water quality guideline for surface water) for a period of 3 h, 12 h, 1 day, 4 days, 10 days, 21 days and 28 days and were either fed (2% body weight) or starved (kept unfed for 7 days prior to sampling). Results showed that the activity of Na + /K +-ATPase in the gills was stimulated by HEA and disturbance in ion balance was obvious with increases in plasma [Na + ], [Cl − ] and [Ca 2+ ] after prolonged exposure. Additionally, osmoregulation and metabolism controlling hormones like cortisol and thyroid hormones (T3 and T4) were investigated to understand adaptive responses. The expression kinetics of growth, stress and osmo-regulatory representative genes such as Insulin-like growth factor 1 (IGF-I), growth hormone receptor (GHR), thyroid hormone receptor ␤ (THR␤), prolactin receptor (PRLR), cortisol receptor (CR) and Na + /K +-ATPase ␣ 3 were examined. Overall effect of HEA was evident since Na + /K +-ATPase activity, plasma cortisol, Na + and Ca 2+ concentration, expression level of CR and Na + /K +-ATPase ␣ 3 mRNA in fed and starved fish were increased. On the contrary, transcript level of PRLR was reduced after 4 days of HEA; additionally T3 level and expression of GHR, IGF-I and THR␤ genes were decreased following 10-21 days of HEA. Starvation, the additional challenge in the present study, significantly increased plasma cortisol level and CR transcript level under HEA compared to the fed exposed and control fish. Furthermore, a remarkable reduction in T3 and mRNA levels of THR␤, IGF-I and GHR genes was observed under starvation. The toxic effects in both feeding treatments were exacerbated when imposed to exhaustive swimming with more pronounced effects in starved fish. This confirms that starvation makes fish more vulnerable to external ammonia, especially during exercise.

Aquatic Toxicology, Oct 1, 2012

Waterborne ammonia has become a persistent pollutant of aquatic habitats. During certain periods ... more Waterborne ammonia has become a persistent pollutant of aquatic habitats. During certain periods (e.g. winter), food deprivation may occur simultaneously in natural water. Additionally, under such stressful circumstances, fish may be enforced to swim at a high speed in order to catch prey, avoid predators and so on. Consequently, fish need to cope with all these stressors by altering physiological processes which in turn are controlled by their genes. In this present study, toxicogenomic analyses using real time PCR was used to characterize expression patterns of potential biomarker genes controlling growth, ion regulation and stress responses in common carp subjected to elevated ammonia (1 mg/L; Flemish water quality guideline for surface water) following periods of feeding (2% body weight) and fasting (unfed for 7 days prior to sampling). Both feeding groups of fish were exposed to high environment ammonia (HEA) for 0 h (control), 3 h, 12 h, 1 day, 4 days, 10 days, 21 days and 28 days, and were sampled after performing swimming at different speeds (routine versus exhaustive). Results show that the activity and expression of Na + /K +-ATPase, an important branchial ion regulatory enzyme, was increased after 4-10 days of exposure. Effect of HEA was also evident on expression patterns of other ion-regulatory hormone and receptor genes; prolactin and cortisol receptor mRNA level(s) were down-regulated and up-regulated respectively after 4, 10 and 21 days. Starvation and exhaustive swimming, the additional challenges in present study significantly further enhanced the HEA effect on the expression of these two genes. mRNA transcript of growth regulating hormone and receptor genes such as Insulin-like growth factor I, growth hormone receptor, and the thyroid hormone receptor were reduced in response to HEA and the effect of ammonia was exacerbated in starved fish, with levels that were remarkably reduced compared to fed exposed fish. However, the expression of the growth hormone gene itself was up-regulated under the same conditions. Expression of somatolactin remained unaltered. Stress representative genes, cytochrome oxidase subunit 1 showed an up-regulation in response to HEA and starvation while the mRNA level of heat shock protein 70 was increased in response to all the three stressors. The expression kinetics of the studied genes could permit to develop a "molecular biomarker system" to identify the underlying physiological processes and impact of these stressors before effects at population level occur.

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2015

Q2 Since hypoxia is a common event in aquatic environments, oxygen has been a major driving force... more Q2 Since hypoxia is a common event in aquatic environments, oxygen has been a major driving force in the evolution of fish. When fish are simultaneously faced with food deprivation in their natural habitat, this poses an even greater challenge to energy and ion homeostasis. In the present study, the combined effects of hypoxia and nutritional status (fed versus fasted) were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8 mg O 2 L −1 , 16-19% saturation at 18°C) at or slightly above their critical oxygen concentration (1.4 mg O 2 L −1 , 16.5% saturation at 20°C) during 1, 3 or 7 days followed by a 7 day recovery period. Fasted fish had lower ventilation frequencies than fed fish but under both feeding regimes, ventilation initially increased during hypoxia. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite its higher ventilation rates). However, during the recovery phase compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous breakdown of liver glycogen indicating increased energy use, while fasting fish seemed to economize energy and recycle decreasing plasma lactate levels into increasing liver glycogen levels (Cori cycle). Protein was used under both feeding regimes during hypoxia and subsequent recovery: protein levels reduced mainly in liver for fed fish and in muscle for fasting fish. Overall, nutritional status had a greater impact on energy reserves than the lack of oxygen with a lower hepatosomatic index and lower glycogen stores in fasted fish. Fasting fish transiently increased Na + /K +-ATPase activity under hypoxia, but in general ionoregulatory balance proved to be only slightly disturbed, showing that sufficient energy was left for ion regulation.

Aquatic Toxicology, Mar 1, 2012

The interactive effects of ammonia exposure, nutritional status and exercise on metabolic and phy... more The interactive effects of ammonia exposure, nutritional status and exercise on metabolic and physiological responses in gold fish (Carassius auratus L.

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, May 1, 2013

Feeding and swimming can influence ion balance in fish. Therefore we investigated their impact on... more Feeding and swimming can influence ion balance in fish. Therefore we investigated their impact on ionoregulation and its hormonal control in goldfish and common carp. As expected due to the osmorespiratory compromise, exhaustive swimming induced increases in gill Na(+)/K(+) ATPase (NKA) activity in both species, resulting in stable levels of plasma ions. In contrast to our expectations, this only occurred in fed fish and feeding itself increased NKA activity, especially in carp. Fasting fish were able to maintain ion balance without increasing NKA activity, we propose that the increase in NKA activity is related to ammonia excretion rather than ion uptake per se. In goldfish, this increase in NKA activity coincided with a cortisol elevation whilst no significant change was found in carp. In goldfish, high conversion of plasma T4 to T3 was found in both fed and fasted fish resulting in low T4/T3 ratios, which increased slightly due to exhaustive swimming. In starved carp the conversion seemed much less efficient, and high T4/T3 ratios were observed. We propose that thyroid hormone regulation in carp was more related to its role in energy metabolism rather than ionoregulation. The present research showed that both species, whether fed or fasted, are able to sufficiently adapt their osmorepiratory strategy to minimise ions losses whilst maintaining gas exchange under exhaustive swimming.

Contamination by heavy metals in aquatic environments is a serious concern due to increasing huma... more Contamination by heavy metals in aquatic environments is a serious concern due to increasing human activities over the last decades. Moreover, productive areas such as estuaries have even been more affected because of the complex interaction between fluvial and marine processes, creating a stressful environment with gradients of salinity and other important parameters which can intensify negative effects of pollutants on biota such as euryhaline fish. (Oliva et al., 2012; Mieiro et al 2012). European sea bass (Dicentrarchus labrax l.) is a euryhaline species able to withstand a large variation in salinity and is considered as a bioindicador due to both economic and ecological importance (Joseph., et al 2011; Loizeau, 2001). Copper as essential micronutrient has important roles in cellular, enzymatical and protein mechanisms but is potentially toxic when its concentration increases above a certain threshold (Blanchard & Grosell, 2005; Grosell et al., 2007), and can even be more toxic...

Exposure to trace metals in toxicity tests is mainly performed at high concentrations, where the ... more Exposure to trace metals in toxicity tests is mainly performed at high concentrations, where the bioaccumulation in tissues and organs are abnormal, while a chronic and long-term exposure, might resembles the field conditions where the organisms usually adapt to this new condition. D. labrax individuals were acutely exposed to Cd concentrations of 1226, 9811 and 12264 μM and Cu concentration of 945, 2269 and 2410 μM over a 10-day period, and to chronically Cd concentration of 997 μM and a Cu concentration of 323 μM over a short period (SEP) of 10-d and long period (LEP) of 28-d, both experiments were conducted at 20‰. Survival time and tissue [Cu] did not show a clear relationship, in contrast, the tissue [Cd] in survivors were about of 5 to 18-fold less accumulated in liver, 10-30-fold in kidney, 12-30-fold in gill and 2-28-fold in intestine than in dead individuals, it appears to be the cause of survival. Liver, kidney, gill and intestine showed significantly higher Cd accumulatio...

Cadmium and copper are constituents of industrial and urban wastes that are considered a concern ... more Cadmium and copper are constituents of industrial and urban wastes that are considered a concern because its environmental levels have risen steadily worldwide (Goering et al., 1995). European sea bass, Dicentrarchus labrax, is an estuary and marine water (EMW) fish that is able to withstand gradients in many physical and chemical variables, including salinity, pH, dissolved oxygen, temperature, nutrients among others. In estuaries, the salinity is the controlling factor for the partitioning of contaminants, trace metals such as cadmium and copper change bioavailability and toxicity by complexation (Riba et al., 2003). Therefore, the effect of salinity on the bioaccumulation and toxicity of copper and cadmium in D. labrax was determined at different exposure concentrations of Cu from 0 to 5100 μg L-1 and Cd from 0 to 20000 μg L-1 over a salinity range of 1, 2.5, 5, 10, 20, 28, 35‰ in juvenile individuals during a period of 10 days. The results showed a relationship between bioaccumu...

Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 2015

In the present study, the combined effects of hypoxia and nutritional status were examined in com... more In the present study, the combined effects of hypoxia and nutritional status were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8mg O2L(-1)) at or slightly above their critical oxygen concentration during 1, 3 or 7days followed by a 7day recovery period. Ventilation initially increased during hypoxia, but fasted fish had lower ventilation frequencies than fed fish. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite higher ventilation rates). However, during recovery, compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous b...

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2013

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2012

Fish need to balance their energy use between digestion and other activities, and different metab... more Fish need to balance their energy use between digestion and other activities, and different metabolic compromises can be pursued. We examined the effects of fasting (7 days) on metabolic strategies in goldfish and common carp at different swimming levels. Fasting had no significant effect on swimming performance (U crit) of either species. Feeding and swimming profoundly elevated total ammonia (T amm) excretion in both species. In fed goldfish, this resulted in increased ammonia quotients (AQ), and additionally plasma and tissue ammonia levels increased with swimming reflecting the importance of protein contribution for aerobic metabolism. In carp, AQ did not change since oxygen consumption (MO 2) and T amm excretion followed the same trend. Plasma ammonia did not increase with swimming suggesting a balance between production and excretion rate except for fasted carp at U crit. While both species relied on anaerobic metabolism during exhaustive swimming, carp also showed increased lactate levels during routine swimming. Fasting almost completely depleted glycogen stores in carp, but not in goldfish. Both species used liver protein for basal metabolism during fasting and muscle lipid during swimming. In goldfish, feeding metabolism was sacrificed to support swimming metabolism with similar MO 2 and U crit between fasted and fed fish, whereas in common carp feeding increased MO 2 at U crit to sustain feeding and swimming independently.

Molecular Cancer Therapeutics, 2022

Fish need to balance their energy use between digestion and other activities, and different metab... more Fish need to balance their energy use between digestion and other activities, and different metabolic compromises can be pursued. We examined the effects of fasting (7 days) on metabolic strategies in goldfish and common carp at different swimming levels. Fasting had no significant effect on swimming performance (U crit ) of either species. Feeding and swimming profoundly elevated total ammonia (T amm ) excretion in both species. In fed goldfish, this resulted in increased ammonia quotients (AQ), and additionally plasma and tissue ammonia levels increased with swimming reflecting the importance of protein contribution for aerobic metabolism. In carp, AQ did not change since oxygen consumption (MO 2 ) and T amm excretion followed the same trend. Plasma ammonia did not increase with swimming suggesting a balance between production and excretion rate except for fasted carp at U crit . While both species relied on anaerobic metabolism during exhaustive swimming, carp also showed increased lactate levels during routine swimming. Fasting almost completely depleted glycogen stores in carp, but not in goldfish. Both species used liver protein for basal metabolism during fasting and muscle lipid during swimming. In goldfish, feeding metabolism was sacrificed to support swimming metabolism with similar MO 2 and U crit between fasted and fed fish, whereas in common carp feeding increased MO 2 at U crit to sustain feeding and swimming independently.

Aquatic toxicology (Amsterdam, Netherlands), 2012

This study aimed to elucidate the physiological effects of high environmental ammonia (HEA) follo... more This study aimed to elucidate the physiological effects of high environmental ammonia (HEA) following periods of feeding (2% body weight) and starvation (unfed for 7 days prior to sampling) in gold fish (Carassius auratus). Both groups of fish were exposed to HEA (1 mg/L; Flemish water quality guideline) for 0 h (control), 3 h, 12 h, 1 day, 4 days, 10 days, 21 days and 28 days. Measurements of weight gain (%), oxygen consumption (MO2), ammonia excretion rate, ammonia quotient (AQ), critical swimming speeds (Ucrit), plasma and muscle ammonia accumulation, plasma lactate, liver and muscle glycogen, lipid and protein content were done at various time intervals during the experimental periods. Overall, ammonia excretion rates, plasma ammonia accumulation and AQ were significantly affected by food regime in ammonia free water. HEA, the additional challenge in the present study, significantly altered all the studied parameters among fed and starved groups in days-dependent manner. Results...

Aquatic toxicology (Amsterdam, Netherlands), Jan 15, 2013

Ammonia is an environmental pollutant that is toxic to all aquatic animals. The toxic effects of ... more Ammonia is an environmental pollutant that is toxic to all aquatic animals. The toxic effects of ammonia can be modulated by other physiological processes such as feeding and swimming. In this study, we wanted to examine these modulating effects in common carp (Cyprinus carpio). Fish were either fed (2% body weight) or starved (unfed for seven days prior to the sampling), and swimming at a sustainable, routine swimming speed or swum to exhaustion, while being exposed chronically (up to 28 days) to high environmental ammonia (HEA, 1 mg/L ~58.8 μmol/L as NH4Cl at pH 7.9). Swimming performance (critical swimming speed, Ucrit) and metabolic responses such as oxygen consumption rate (MO2), ammonia excretion rate (Jamm), ammonia quotient, liver and muscle energy budget (glycogen, lipid and protein), plasma ammonia and lactate, as well as plasma ion concentrations (Na(+), Cl(-), K(+) and Ca(2+)) were investigated in order to understand metabolic and iono-regulatory consequences of the expe...

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2013

Feeding and swimming can influence ion balance in fish. Therefore we investigated their impact on... more Feeding and swimming can influence ion balance in fish. Therefore we investigated their impact on ionoregulation and its hormonal control in goldfish and common carp. As expected due to the osmorespiratory compromise, exhaustive swimming induced increases in gill Na + /K + ATPase (NKA) activity in both species, resulting in stable levels of plasma ions. In contrast to our expectations, this only occurred in fed fish and feeding itself increased NKA activity, especially in carp. Fasting fish were able to maintain ion balance without increasing NKA activity, we propose that the increase in NKA activity is related to ammonia excretion rather than ion uptake per se. In goldfish, this increase in NKA activity coincided with a cortisol elevation whilst no significant change was found in carp. In goldfish, high conversion of plasma T 4 to T 3 was found in both fed and fasted fish resulting in low T 4 /T 3 ratios, which increased slightly due to exhaustive swimming. In starved carp the conversion seemed much less efficient, and high T 4 /T 3 ratios were observed. We propose that thyroid hormone regulation in carp was more related to its role in energy metabolism rather than ionoregulation. The present research showed that both species, whether fed or fasted, are able to sufficiently adapt their osmorepiratory strategy to minimise ions losses whilst maintaining gas exchange under exhaustive swimming.

Investigative ophthalmology & visual science, Mar 1, 2017

Aquatic Toxicology, Jun 1, 2012

Aquatic Toxicology, Oct 1, 2012

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2015

Aquatic Toxicology, Mar 1, 2012

Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, May 1, 2013

Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 2015

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2013

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2012

Molecular Cancer Therapeutics, 2022

Fish need to balance their energy use between digestion and other activities, and different metab... more Fish need to balance their energy use between digestion and other activities, and different metabolic compromises can be pursued. We examined the effects of fasting (7 days) on metabolic strategies in goldfish and common carp at different swimming levels. Fasting had no significant effect on swimming performance (U crit ) of either species. Feeding and swimming profoundly elevated total ammonia (T amm ) excretion in both species. In fed goldfish, this resulted in increased ammonia quotients (AQ), and additionally plasma and tissue ammonia levels increased with swimming reflecting the importance of protein contribution for aerobic metabolism. In carp, AQ did not change since oxygen consumption (MO 2 ) and T amm excretion followed the same trend. Plasma ammonia did not increase with swimming suggesting a balance between production and excretion rate except for fasted carp at U crit . While both species relied on anaerobic metabolism during exhaustive swimming, carp also showed increased lactate levels during routine swimming. Fasting almost completely depleted glycogen stores in carp, but not in goldfish. Both species used liver protein for basal metabolism during fasting and muscle lipid during swimming. In goldfish, feeding metabolism was sacrificed to support swimming metabolism with similar MO 2 and U crit between fasted and fed fish, whereas in common carp feeding increased MO 2 at U crit to sustain feeding and swimming independently.

Aquatic toxicology (Amsterdam, Netherlands), 2012

Aquatic toxicology (Amsterdam, Netherlands), Jan 15, 2013

Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2013

Feeding and swimming can influence ion balance in fish. Therefore we investigated their impact on... more Feeding and swimming can influence ion balance in fish. Therefore we investigated their impact on ionoregulation and its hormonal control in goldfish and common carp. As expected due to the osmorespiratory compromise, exhaustive swimming induced increases in gill Na + /K + ATPase (NKA) activity in both species, resulting in stable levels of plasma ions. In contrast to our expectations, this only occurred in fed fish and feeding itself increased NKA activity, especially in carp. Fasting fish were able to maintain ion balance without increasing NKA activity, we propose that the increase in NKA activity is related to ammonia excretion rather than ion uptake per se. In goldfish, this increase in NKA activity coincided with a cortisol elevation whilst no significant change was found in carp. In goldfish, high conversion of plasma T 4 to T 3 was found in both fed and fasted fish resulting in low T 4 /T 3 ratios, which increased slightly due to exhaustive swimming. In starved carp the conversion seemed much less efficient, and high T 4 /T 3 ratios were observed. We propose that thyroid hormone regulation in carp was more related to its role in energy metabolism rather than ionoregulation. The present research showed that both species, whether fed or fasted, are able to sufficiently adapt their osmorepiratory strategy to minimise ions losses whilst maintaining gas exchange under exhaustive swimming.