Future Ecological Risk Assessment: “Status Humana,” Man as the Measure

The current environmental paradigm of attempting to maintain, to the extent possible, the “status quo” is intellectually dishonest and untenable. Man has long been at least implicitly recognized as “the measure of all things.” Ecological risk assessments (ERAs) need to be based on the reality that humans have primacy in nature and are a major evolutionary force, albeit a selfish one: the “status humana” paradigm. A variety of facts are set out in support of this paradigm and to demonstrate both its relevance and its value. Examples of applications of this paradigm include hormesis, chemicals, food production and biodiversity, socioeconomic and environmental issues, ecotoxicology and bioavailability, introduced species, and environmental relevance.     

Ultraviolet irradiation increases size of the first clutch but decreases longevity in a marine copepod

An important component of life history theory is understanding how natural variation arises in populations. Both endogenous and exogenous factors contribute to organism survival and reproduction, and therefore, it is important to understand how such factors are both beneficial and detrimental to population dynamics. One ecologically relevant factor that influences the life history of aquatic organisms is ultraviolet (UV) radiation. While the majority of research has focused on the potentially detrimental effects that UV radiation has on aquatic organisms, few studies have evaluated hormetic responses stimulated by radiation under select conditions. The goal of this study was to evaluate the impact of UV‐A/B irradiation on life history characteristics in Tigriopus californicus copepods. After exposing copepods to UV‐A/B irradiation (control, 1‐, and 3‐hr UV treatments at 0.5 W/m²), we measured the impact of exposure on fecundity, reproductive effort, and longevity. We found that UV irradiation increased the size of the first clutch among all reproducing females in both the 1‐ and 3‐hr experimental groups and decreased longevity among all females that mated in the 1‐hr treatment. UV irradiation had no effect on the number of clutches females produced. These findings indicate a potential benefit of UV irradiation on reproductive performance early in life, although the same exposure came at a cost to longevity.     

HORMESIS RESULTS IN TRADE‐OFFS WITH IMMUNITY

Many have argued that we may be able to extend life and improve human health through hormesis, the beneficial effects of low‐level toxins and other stressors. But, studies of hormesis in model systems have not yet established whether stress‐induced benefits are cost free, artifacts of inbreeding, or come with deleterious side effects. Here, we provide evidence that hormesis results in trade‐offs with immunity. We find that a single topical dose of dead spores of the entomopathogenic fungus, Metarhizium robertsii, increases the longevity of the fruit fly, Drosophila melanogaster, without significant decreases in fecundity. We find that hormetic benefits of pathogen challenge are greater in lines that lack key components of antifungal immunity (Dif and Turandot M). And, in outbred fly lines, we find that topical pathogen challenge enhances both survival and fecundity, but reduces ability to fight off live infections. The results provide evidence that hormesis is manifested by stress‐induced trade‐offs with immunity, not cost‐free benefits or artifacts of inbreeding. Our findings illuminate mechanisms underlying pathogen‐induced life‐history trade‐offs, and indicate that reduced immune function may be an ironic side effect of the “elixirs of life.”     

Optimal conditions of LDR to protect the kidney from diabetes: Exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes

Aims

We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes.

Main methods

Male C57BL/6J mice with type 1 diabetes were induced with multiple injections of low-dose streptozotocin. Diabetic mice received whole body X-irradiation at a dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th weeks of the study.

Key findings

Diabetes induced renal dysfunction is shown by the decreased creatinine and increased microalbumin in the urine. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best protective effect on the kidney of diabetic mice.

Significance

Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes.     

The Concept of Hormesis in Developmental Toxicology

Animal bioassay experiments are frequently conducted to assess the toxicity of chemicals on the developing fetus. Experiments are normally conducted at dosage levels that are much higher than human exposure levels to elicit the toxic reproductive effect of the chemical in a limited number of litters. Recently there has been much discussion on the fact that some chemicals may have beneficial effects at low doses and become toxic at high doses. This concept, known as chemical hormesis, has been the focus of attention in many investigations. Here, we consider the prevalence of hormesis in developmental toxicology and show that current design of developmental toxicity testing does not accommodate the study of hormesis. If it can be proved that some developmental toxicants may have stimulatory low dose effects, then design and analysis of developmental toxicity experiments need to be revised by the scientific community and the regulatory agencies. Using a thorough analysis of an experimental data set, we further demonstrate that in order to establish the possible hormetic effects of a chemical in reproduction, often a multiple replication of the experiment may be necessary to examine such effects. Using a trend test, we illustrate that while it is possible that one replicate of a developmental toxicity experiment with a known teratogen shows strong evidence of hormesis, other replicates may show no sign of beneficial effects at low doses.     

The effect of pH onBrachionus calyciflorus Pallas (Rotifera)

Cohorts of the rotiferBrachionus calyciflorus were grown in media with pH of between 2.5 and 11.5 in increments of 1 unit. pH was shown to exert a major influence on the growth rate and reproductive capacity of theB. calyciflorus. At pH 2.5 theB. calyciflorus showed a negative capacity for population increase (r _c). Ther _c values of the cohorts reared at pH 3.5 and 4.5 were positive and these cohorts showed high net reproductive rates (R₀). Ther _c's of cohorts reared at pH of 5.5 and 6.5 were negative, while those of cohorts reared at pH 7.5 to 10.5 were positive with a peak in theR ₀ and cohort generation time (T _c) at pH 8.5 and 9.5. Total mortality occurred in less that 24 h at pH 11.5.Successive generations of the progeny from the cohort held at pH 3.5 were reared under the same conditions. Although ther _c of the F₁ and F₂ cohorts increased, the organism was unable to maintain the increased population growth rate, and the F₄ generation showed anr _c of almost 0.     

Cold pre-conditioning neuroprotection depends on TNF-α and is enhanced by blockade of interleukin-11

Cold pre-conditioning reduces subsequent brain injury in small animals but the underlying mechanisms remain undefined. As hypothermia triggers systemic macrophage tumor necrosis factor alpha (TNF-α) production and other neural pre-conditioning stimuli depend on this cytokine, we reasoned that microglia and TNF-α would be similarly involved with cold pre-conditioning neuroprotection. Also, as slice cultures closely approximate their in vivo counterpart and include quiescent microglia, we used rat hippocampal slice cultures to confirm this hypothesis. Furthermore, inflammatory cytokine gene screening with subsequent PCR and immunostaining confirmation of targeted mRNA and related protein changes showed that cold pre-conditioning triggered a significant rise in TNF-α that localized to microglia and a significant rise in interleukin (IL)-11 that localized mainly to hippocampal pyramidal neurons and, more rarely, astrocytes. Importantly, co-stimulation with cold and IL-11, an anti-inflammatory cytokine that inhibits TNF-α expression, abrogated the otherwise evident protection. Instead, cold pre-conditioning coupled with blockade of IL-11 signaling further enhanced neuroprotection from that seen with cold pre-conditioning alone. Thus, physiological activation of brain pro-inflammatory cytokine signaling, and its amplification by inhibition of coincident anti-inflammatory cytokine signaling, may be opportune targets for the development of novel therapeutics that can mimic the protection seen in cold pre-conditioning.     

Endocannabinoids in neuroendopsychology: multiphasic control of mitochondrial function

The endocannabinoid system (ECS) is a construct based on the discovery of receptors that are modulated by the plant compound tetrahydrocannabinol and the subsequent identification of a family of nascent ligands, the ‘endocannabinoids’. The function of the ECS is thus defined by modulation of these receptors—in particular, by two of the best-described ligands (2-arachidonyl glycerol and anandamide), and by their metabolic pathways. Endocannabinoids are released by cell stress, and promote both cell survival and death according to concentration. The ECS appears to shift the immune system towards a type 2 response, while maintaining a positive energy balance and reducing anxiety. It may therefore be important in resolution of injury and inflammation. Data suggest that the ECS could potentially modulate mitochondrial function by several different pathways; this may help explain its actions in the central nervous system. Dose-related control of mitochondrial function could therefore provide an insight into its role in health and disease, and why it might have its own pathology, and possibly, new therapeutic directions.