Determination of in vivo toxicity and in vitro cytotoxicity of venom from the Cypriot blunt-nosed viper Macrovipera lebetina lebetina and antivenom production

The venomous Levantine viper, Macrovipera lebetina lebetina is endemic to Cyprus. The objective of this study was to investigate in vitro cytotoxicity, in vivo lethality, and antivenom production followed by a re-immunization schedule in mice against Macrovipera lebetina lebetina venom. The LD50 value was estimated as 7.58 mg/kg within 24 hours by different venom doses administrated intraperitoneally in mice. Freund's complete and incomplete adjuvants were used for first and second immunization of mice in antivenom production. A cell-based assay was performed to determine the effects of Macrovipera lebetina lebetina venom and antivenom neutralizing potency on L929 cell viability. The snake venom toxicity and cytotoxicity were examined and comparison of results showed good correlation, the LD50 value was tenfold higher than the IC50 value. The IC50 value was 0.62 ± 0.18 mL after 48 hours treatment while the calculated value was 1.62 ± 0.25 mL for the culture media totally refreshed after two hours treatment with venom. The in vitro efficacy of antivenom against Macrovipera lebetina lebetina venom was found to be low. This is the first report that describes the in vivo and in vitro toxic effects of Macrovipera lebetina lebetina venom and antivenom production against this species.(AU)

Effects of Pinus brutia bark extract and Pycnogenol in a rat model of carrageenan induced inflammation.

The present study was conducted to explore the anti-inflammatory activities of Pinus brutia bark extract and Pycnogenol in a rat model of carrageenan-induced inflammation. Firstly, the compositions of both samples were determined using HPLC. Then, carrageenan-induced paw edema was used to assess anti-inflammatory activity in mice. Paw volume was measured before and 1, 2, 3, 4, 5 and 6h after the injection of carrageenan. Intraperitoneal administration of both the extract and Pycnogenol inhibited paw swelling dose-dependently at 2, 3, 4, 5 and 6h after carrageenan injection. Both samples exhibited significant anti-inflammatory activities at doses of 75 and 100 mg/kg body wt. between 2 and 4 hours after administration (p<0.05), respectively. Additionally, P. brutia bark extract showed significantly better activity at doses of 75 and 100mg/kg body wt. than indomethacine at the dose of 10mg/kg body wt. (p<0.05). No acute toxicity was identified in intraplantar injection of the extract at a dose of 2000 mg/kg body wt.. Therefore, P. brutia bark extract possessing 3.3-fold more total catechins and 9.8-fold more taxifolin than Pycnogenol can be utilized as an anti-inflammatory agent.