Humoral signalling compounds in remote ischaemic preconditioning of the kidney, a role for the opioid receptor.

Item does not contain fulltextBACKGROUND: Renal ischaemia-reperfusion injury (IRI) is a common clinical problem associated with significant mortality and morbidity. One strategy to reduce this damage is remote ischaemic preconditioning (RIPC), in which brief ischaemia of a limb protects the kidney against a prolonged ischaemic insult. The mechanism of renal RIPC has not yet been elucidated. Here, we address the gap in our understanding of renal RIPC signalling, using a rat model of renal IRI and RIPC by brief hind limb ischaemia. METHODS: Rats were treated with either no RIPC, RIPC + vehicle or RIPC+ an inhibitor or antagonist of one of the following candidate signalling molecules: noradrenalin, cannabinoids, glucocorticoids, inducible nitric oxide synthase, calcitonin gene-related peptide, ganglion-mediated signalling, haem oxygenase and free radicals. Subsequently, the animals underwent 25 min of renal ischaemia and 2 days of reperfusion, after which renal function and damage were assessed. RESULTS: RIPC by three 4 min cycles of hind limb ischaemia effectively reduced renal IRI. Pre-treatment with the opioid receptor antagonist naloxone completely blocked this protective effect, when compared with animals treated with RIPC + vehicle; serum creatinine and urea increased (307.8 +/- 43.7 versus 169.5 +/- 16.7 micromol/L and 42.2 +/- 4.9 versus 27.6 +/- 2.2 mmol/L, respectively), as did the renal histological damage (score 4.2 +/- 0.7 versus 2.8 +/- 0.5) and expression of kidney injury molecule-1 (KIM-1; relative-fold increase in mRNA expression 164 +/- 18 versus 304 +/- 33). All other antagonists were without effect. CONCLUSIONS: Renal RIPC by brief hind limb ischaemia may be the result of endorphin release from the hind limb. The importance of opioid signalling in renal RIPC provides vital clues for its successful translation to the clinical setting.1 juli 201

Assessment of safety/risk vs. Public health concerns: Aflatoxins and hepatocarcinoma

Hepatocellular carcinoma, (HCC) is a serious health problem. It is prevalent in certain parts of the world where food contamination with aflatoxin is common. Aflatoxin, especially AFB1, has been shown to induce HCC in many species of laboratory and wild animals, including subhuman primates. Carcinogenesis studies have demonstrated that AFB1 is a potent genotoxic carcinogen. After bioactivation it may covalently bind with protein and with DNA. The former reaction is positively correlated with AFB1 exposure, and the latter signifies initiation of the carcinogenesis process