Is “Preparation for Oxidative Stress” a Case of Physiological Conditioning Hormesis?

Oliveira, Marcus F.; Geihs, Márcio Alberto; França, Thiago F. A.; Moreira, Daniel C.; Hermes‐Lima, Marcelo

doi:10.3389/fphys.2018.00945

Cited by 68 publications

(45 citation statements)

References 64 publications

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“…Moreover, we observed a positive correlation between the ORAC levels and animal body size across the treatments indicating a possible primary mechanism behind the observed effects being a hormetic shifting of redox environment by the pro-oxidative Ciprofloxacin, antioxidant response and the resulting beneficial effects on growth. Such effects are in agreement with a concept of physiological conditional hormesis [55] and suggest a possible mechanism for the direct response of Daphnia magna to Ciprofloxacin exposure at environmentally relevant concentrations. An important caveat is that hormesis, also shown to occur in several microbes' response to quinolones and fluoroquinolones (the so-called paradoxical effect) [56] might be universal and thus Ciprofloxacin may be a suboptimal choice for the uncomplicated study on microbiome involvement in dose-response relationships with the host.…”

Section: Effects Of Ciprofloxacin On Life History Traits and Antioxidsupporting

confidence: 86%

Disparate effects of antibiotic-induced microbiome change and enhanced fitness in Daphnia magna

et al. 2020

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It is a common view that an organism's microbiota has a profound influence on host fitness; however, supporting evidence is lacking in many organisms. We manipulated the gut microbiome of Daphnia magna by chronic exposure to different concentrations of the antibiotic Ciprofloxacin (0.01-1 mg L-1), and evaluated whether this affected the animals fitness and antioxidant capacity. In line with our expectations, antibiotic exposure altered the microbiome in a concentration-dependent manner. However, contrary to these expectations, the reduced diversity of gut bacteria was not associated with any fitness detriment. Moreover, the growth-related parameters correlated negatively with microbial diversity; and, in the daphnids exposed to the lowest Ciprofloxacin concentrations, the antioxidant capacity, growth, and fecundity were even higher than in control animals. These findings suggest that Ciprofloxacin exerts direct stimulatory effects on growth and reproduction in the host, while microbiome-mediated effects are of lesser importance. Thus, although microbiome profiling of Daphnia may be a sensitive tool to identify early effects of antibiotic exposure, disentangling direct and microbiome-mediated effects on the host fitness is not straightforward.

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Section: Effects Of Ciprofloxacin On Life History Traits and Antioxidsupporting

confidence: 86%

Disparate effects of antibiotic-induced microbiome change and enhanced fitness in Daphnia magna

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Moreover, we observed a positive correlation between the ORAC levels and animal body size across the treatments indicating a possible primary mechanism behind the observed effects being a hormetic shifting of redox environment by pro-oxidative ciprofloxacin, antioxidant response and the resulting beneficial effects on growth. Such effects are in agreement with a concept of physiological conditional hormesis (55) and suggest a possible mechanism for the direct response of Daphnia magna to Ciprofloxacin exposure at environmentally relevant concentrations. An important caveat is that hormesis, also shown to occur in several microbes’ response to quinolones and fluoroquinolones (the so-called paradoxical effect) (56) might be universal and thus ciprofloxacin may be suboptimal for the uncomplicated study on microbiome involvement following dose-response relationships.…”

Section: Discussionsupporting

confidence: 86%

Disparate effects of antibiotic-induced microbiome change and enhanced fitness inDaphnia magna

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Brindefalk

Ogonowski

et al. 2019

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13It is a common view that an organism's microbiota has a profound influence on host fitness; 14 however, supporting evidence is lacking in many organisms. We manipulated the gut 15 microbiome of Daphnia magna by chronic exposure to different concentrations of the 16 antibiotic Ciprofloxacin (0.01 -1 mg L -1 ), and evaluated whether this affected the animals' 17 fitness and antioxidant capacity. In line with our expectations, antibiotic exposure altered the 18 microbiome in a concentration-dependent manner. However, contrary to these expectations, 19 the reduced diversity of gut bacteria was not associated with any fitness detriment. Moreover, 20 the growth-related parameters correlated negatively with diversity indices; and, in the 21 daphnids exposed to the lowest ciprofloxacin concentrations, the antioxidant capacity, 22 growth, and fecundity were even higher than in control animals. These findings suggest that 23 ciprofloxacin exerts direct stimulatory effects on growth and reproduction in Daphnia, while 24 microbiome-mediated effects are of lesser importance. Thus, although microbiome profiling 25 of Daphnia may be a sensitive tool to identify early effects of antibiotic exposure, 26 disentangling direct and microbiome-mediated effects on host fitness is not straightforward. 27 68 sequencing (22 , 23). Regardless of the sequencing platform, origin of specimens, and culture 69 conditions, the core microbiome appears relatively stable, mainly comprised of 70 Betaproteobacteria, Gammaproteobacteria and facultative anaerobic Bacteroidetes species. 71At the genus level, Limnohabitans has been reported as one of the most stable and dominant 72 members in Daphnia gut, and variations in its abundance have been tied to the animal 73 fecundity (22). Although some studies have addressed the dependence of Daphnia on its 74 microbiota (9) and some short-term effects on fitness following exposure to antibiotics have 75 been observed in Daphnia magna (25, 13), the relationship between microflora perturbation 76 and host fitness is still unclear, as is the involvement and modulating role of antioxidants in 77 these relationships. 78In this study, the relationship between antibiotic-mediated gut microbiome modulation and 79 host fitness were addressed experimentally using a model cladoceran Daphnia magna. We 80 monitored changes in the gut microbiome, host longevity, growth, and reproduction, as well 81 as antioxidant levels in the exposed animals following ciprofloxacin exposure. We 82 hypothesized that the diversity and abundance of the gut-associated microflora would 83 decrease with increasing concentration of antibiotics. Furthermore, we expected longer 84 exposure time and higher antibiotic concentrations to have negative effects on somatic 85 growth, reproductive output, and antioxidant capacity. These reductions we expected would 86 be due to reduced bacterial diversity in particular, and to some extent, an altered community 87 composition. These hypotheses were tested by combining (1) long-term (21 d) exposure...

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“…We hypothesize that CBD, similar to other stressors, may protect neurons via this increased stress response and thereby confer tolerance to additional oxidant insults. This phenomenon is called "preparation for oxidative stress" [53], and explains the mechanism underlying the protective conditioning effects. CBD has been shown to act as neuroprotective agent against stressful conditions in several in-vivo and in-vitro models [7][8][9][54][55][56][57], possessing antioxidant and anti-inflammatory activity [58].…”

Section: Experimental Models To Study Neurodegeneration and The Mechamentioning

confidence: 99%

Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin

et al. 2020

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Phytocannabinoids protect neurons against stressful conditions, possibly via the heme oxygenase (HO) system. In cultures of primary mesencephalic neurons and neuroblastoma cells, we determined the capability of cannabidiol (CBD) and tetrahydrocannabinol (THC) to counteract effects elicited by complex I-inhibitor rotenone by analyzing neuron viability, morphology, gene expression of IL6, CHOP, XBP1, HO-1 (stress response), and HO-2, and in vitro HO activity. Incubation with rotenone led to a moderate stress response but massive degeneration of dopaminergic neurons (DN) in primary mesencephalic cultures. Both phytocannabinoids inhibited in-vitro HO activity, with CBD being more potent. Inhibition of the enzyme reaction was not restricted to neuronal cells and occurred in a non-competitive manner. Although CBD itself decreased viability of the DNs (from 100 to 78%), in combination with rotenone, it moderately increased survival from 28.6 to 42.4%. When the heme degradation product bilirubin (BR) was added together with CBD, rotenone-mediated degeneration of DN was completely abolished, resulting in approximately the number of DN determined with CBD alone (77.5%). Using N18TG2 neuroblastoma cells, we explored the neuroprotective mechanism underlying the combined action of CBD and BR. CBD triggered the expression of HO-1 and other cell stress markers. Co-treatment with rotenone resulted in the super-induction of HO-1 and an increased in-vitro HO-activity. Co-application of BR completely mitigated the rotenone-induced stress response. Our findings indicate that CBD induces HO-1 and increases the cellular capacity to convert heme when stressful conditions are met. Our data further suggest that CBD via HO may confer full protection against (oxidative) stress when endogenous levels of BR are sufficiently high.

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Is “Preparation for Oxidative Stress” a Case of Physiological Conditioning Hormesis?

Cited by 68 publications

References 64 publications

Disparate effects of antibiotic-induced microbiome change and enhanced fitness in Daphnia magna

Disparate effects of antibiotic-induced microbiome change and enhanced fitness in Daphnia magna

Disparate effects of antibiotic-induced microbiome change and enhanced fitness inDaphnia magna

Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin

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