Fish feed can show genotoxic damage.

The present study was carried out to evaluate the genotoxic potential of nutritional quality of feed, using erythrocytic nuclear abnormalities assay in Nile tilapia and its correlation with available nutrients and common fish growth biomarkers. For this, ten feeds commercialized in Brazil were assessed on digestibility and performance assays with triplicate groups. Venipuncture of the caudal vein for abnormalities analyzed was performed 102 days after the fish were fed with the commercial feed twice a day, to apparent satiation. Nuclear abnormalities were analyzed in blood smears. Principal component analysis and correlation matrix were used to carry out an exploratory analysis of correlation between frequency of abnormalities and performance parameters or available nutrients. The frequency of abnormalities in erythrocytes of Nile tilapia, fish performance, and digestibility were feed-dependent. It was observed correlations between the frequency of most abnormalities and performance parameters or content of nutrients. The frequency of kidney-shaped (6.23 ± 4.14), bud nuclei (2.99 ± 1.95), bridge nuclei (0.53 ± 0.50), and binuclei (0.43 ± 0.59) was the highest in fish that also presented the worst performance among all treatments and correlated with digestible methionine. Micronucleus frequency (0.33 ± 0.49) was higher in fish from the same group that presented depressed feed intake and lower available zinc. Only one group presented vacuolated nuclei and the frequency of this abnormality was correlated with available phosphorus. The frequency of abnormalities in erythrocytes is a fish sensitive indicator of health and plays an important role as a complementary tool in the assessment of fish feeding. The variation in the frequency of nuclear abnormalities in erythrocytes obtained among fish fed with the different feeds allows the assertion that they contained genotoxic factors.

Identification of the plant steroid α-spinasterol as a novel transient receptor potential vanilloid 1 antagonist with antinociceptive properties.

The transient receptor potential vanilloid 1 (TRPV1) receptor is relevant to the perception of noxious information and has been studied as a therapeutic target for the development of new analgesics. The goal of this study was to perform in vivo and in vitro screens to identify novel, efficacious, and safe TRPV1 antagonists isolated from leaves of the medicinal plant Vernonia tweedieana Baker. All of the fractions and the hydroalcoholic extract produced antinociception in mice during the capsaicin test, but the dichloromethane fraction also had antioedematogenic effect. Among the compounds isolated from the dichloromethane fraction, only α-spinasterol reduced the nociception and edema induced by capsaicin injection. Moreover, α-spinasterol demonstrated good oral absorption and high penetration into the brain and spinal cord of mice. α-Spinasterol was able to displace [3H]resiniferatoxin binding and diminish calcium influx mediated by capsaicin. Oral administration of the dichloromethane fraction and α-spinasterol also produced antinociceptive effect in the noxious heat-induced nociception test; however, they did not change the mechanical threshold of naive mice. The treatment with α-spinasterol did not produce antinociceptive effect in mice systemically pretreated with resiniferatoxin. In addition, α-spinasterol and the dichloromethane fraction reduced the edema, mechanical, and heat hyperalgesia elicited by complete Freund's adjuvant paw injection. The dichloromethane fraction and α-spinasterol did not affect body temperature or locomotor activity. In conclusion, α-spinasterol is a novel efficacious and safe antagonist of the TRPV1 receptor with antinociceptive effect.

Eriodictyol: a flavonoid antagonist of the TRPV1 receptor with antioxidant activity.

The transient potential vanilloid 1 receptor (TRPV1) is a calcium-permeable channel responsible for the transduction and modulation of acute and chronic pain signaling. As such, this receptor is a potential target for the treatment of a number of pain disorders. However, AMG517, a TRPV1 antagonist, presents several clinical limitations that include the induction of severe hyperthermia. The aim of this study was to investigate the possible interaction of the flavonoid eriodictyol with the TRPV1 receptor and to determine its putative antinociceptive and hyperthermic effects. Eriodictyol was able to displace [(3)H]-resiniferatoxin binding (IC(50)=47; 21-119nM) and to inhibit calcium influx mediated by capsaicin (IC(50)=44; 16-125nM), suggesting that eriodictyol acts as a TRPV1 antagonist. Moreover, eriodictyol induced antinociception in the intraplantar capsaicin test, with maximal inhibition of 49±10 and 64±4% for oral (ID(50)=2.3; 1.1-5.7mg/kg) and intrathecal (ID(50)=2.2; 1.7-2.9nmol/site) administration, respectively. Eriodictyol did not induce any change in body temperature or locomotor activity. Orally administered eriodictyol (4.5mg/kg) prevented the nociception induced by intrathecal injections of capsaicin, as well as the non-protein thiol loss and 3-nitrotyrosine (3-NT) formation induced by capsaicin in spinal cord. Eriodictyol also reduced the thermal hyperalgesia and mechanical allodynia elicited by complete Freund's adjuvant (CFA) paw injection. In conclusion, eriodictyol acts as an antagonist of the TRPV1 receptor and as an antioxidant; it induces antinociception without some of the side effects and limitations such as hyperthermia that are expected for TRPV1 antagonists.