SUMMARY Cadmium (Cd) is a heavy metal found as an environmental contaminant, both through natural occurrence and from industrial and agricultural sources. Foodstuffs are the main source of cadmium exposure for the non-smoking general population. Cadmium absorption after dietary exposure in humans is relatively low (3–5 %) but cadmium is efficiently retained in the kidney and liver in the human body, with a very long biological half-life ranging from 10 to 30 years. Cadmium is primarily toxic to the kidney, especially to the proximal tubular cells where it accumulates over time and may cause renal dysfunction. Cadmium can also cause bone demineralisation, either through direct bone damage or indirectly as a result of renal dysfunction. After prolonged and/or high exposure the tubular damage may progress to decreased glomerular filtration rate, and eventually to renal failure. The International Agency for Research on Cancer has classified cadmium as a human carcinogen (Group 1) on the basis of occupational studies. Newer data on human exposure to cadmium in the general population have been statistically associated with increased risk of cancer such as in the lung, endometrium, bladder, and breast. Cadmium bioavailability, retention and consequently toxicity are affected by several factors such as nutritional status (low body iron stores) and multiple pregnancies, preexisting health conditions or diseases. A health based guidance value for cadmium of 7 μg/kg body weight (b.w.) per week (Provisional Tolerable Weekly Intake (PTWI)) was established previously by the Joint 1 For citation purposes: Scientific Opinion of the Panel on Contaminants in the Food Chain on a request from the European

/pdf/scientific-opinion-of-the-panel-on-contaminants-in-the-food-4g58bdunry.pdf

Scientific Opinion of the Panel on Contaminants in the Food Chain

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/S0014-5793%2803%2901447-9

Microcystin-LR and okadaic acid-induced cellular effects: a dualistic response

https://kops.uni-konstanz.de/bitstream/handle/123456789/8246/Microcystin_LR_Toxicodynamics.pdf;sequence=1

Microcystin-LR toxicodynamics, induced pathology, and immunohistochemical localization in livers of blue-green algae exposed rainbow trout (oncorhynchus mykiss).

The protein phosphatase (PP) inhibitors nodularin and microcystin-LR induced apoptosis with unprecedented rapidity, more than 50% of primary hepatocytes showing extensive surface budding and shrinkage of cytoplasm and nucleoplasm within 2 min. The apoptosis was retarded by the general caspase inhibitor Z-VAD.fmk. To circumvent the inefficient uptake of microcystin and nodularin into nonhepatocytes, toxins were microinjected into 293 cells, Swiss 3T3 fibroblasts, promyelocytic IPC-81 cells, and NRK cells. All cells started to undergo budding typical of apoptosis within 0.5–3 min after injection. This was accompanied by cytoplasmic and nuclear shrinkage and externalization of phosphatidylserine. Overexpression of Bcl-2 did not delay apoptosis. Apoptosis induction was slower and Z-VAD.fmk independent in caspase-3 deficient MCF-7 cells. MCF-7 cells stably transfected with caspase-3 showed a more rapid and Z-VAD.fmk dependent apoptotic response to nodularin. Rapid apoptosis induction required inhibition of both PP1 and PP2A, and the apoptosis was preceded by increased phosphorylation of several proteins, including myosin light chain. The protein phosphorylation occurred even in the presence of apoptosis-blocking concentrations of Z-VAD.fmk, indicating that it occurred upstream of caspase activation. It is suggested that phosphatase-inhibiting toxins can induce caspase-3 dependent apoptosis in an ultrarapid manner by altering protein phosphorylation.

/pdf/ultrarapid-caspase-3-dependent-apoptosis-induction-by-serine-5e7fd36a8x.pdf

Ultrarapid caspase-3 dependent apoptosis induction by serine/threonine phosphatase inhibitors

Aqueous extracts and organic solvent extracts of isolated marine cyanobacteria strains were tested for antimicrobial activity against a fungus, Gram-positive and Gram-negative bacteria and for cytotoxic activity against primary rat hepatocytes and HL-60 cells. Antimicrobial activity was based on the agar diffusion assay. Cytotoxic activity was measured by apoptotic cell death scored by cell surface evaluation and nuclear morphology. A high percentage of apoptotic cells were observed for HL-60 cells when treated with cyanobacterial organic extracts. Slight apoptotic effects were observed in primary rat hepatocytes when exposed to aqueous cyanobacterial extracts. Nine cyanobacteria strains were found to have antibiotic activity against two Gram-positive bacteria, Clavibacter michiganensis subsp. insidiosum and Cellulomonas uda. No inhibitory effects were found against the fungus Candida albicans and Gram-negative bacteria. Marine Synechocystis and Synechococcus extracts induce apoptosis in eukaryotic cells and cause inhibition of Gram-positive bacteria. The different activity in different extracts suggests different compounds with different polarities.

/pdf/antimicrobial-and-cytotoxic-assessment-of-marine-2woa6okbrc.pdf

Nina Lied Larsen

Papers

Sensitive detection of apoptogenic toxins in suspension cultures of rat and salmon hepatocytes