Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice

Abstract

Carvacrol is a compound isolated from some essential oils. It has been reported to possess anthelmintic activity. Acetylation of this monoterpene has been proposed as a potential way to reduce the toxicity and enhance the pharmacological effects of carvacrol. This study aimed to evaluate the effect of carvacryl acetate (CA) using in vitro and in vivo assays with gastrointestinal nematodes of small ruminants. The egg hatching test (EHT), larval development test (LDT) and adult worm motility (AWM) assessment were conducted to evaluate the effect of the acetylated product and pure carvacrol on Haemonchus contortus eggs, larvae and adults. The structural changes induced in adult H. contortus were assessed using scanning electron microscopy (SEM). CA and carvacrol acute toxicity was evaluated in mice. Finally, the efficacy of 250 mg/kg CA and 2.5mg/kg monepantel (positive control) were evaluated in 30 sheep naturally infected with gastrointestinal nematodes by the fecal egg count reduction test (FECRT). In vitro tests were analyzed by analysis of variance (ANOVA) followed by comparison with Tukey's test. The efficacy was calculated by the Boot Street program using the arithmetic average. The number of eggs in feces (epg) of the groups were transformed to log (x+1) and subjected to ANOVA to compare differences among the groups by Tukey's test. The level of significance was P<0.05. CA and carvacrol inhibited larval hatching by 89.3 and 97.7% at doses of 8.0 and 1.0mg/ml, respectively. At the concentration of 2mg/ml, CA and carvacrol inhibited 100% of larval development. At a concentration of 200 μg/ml, CA and carvacrol inhibited the motility of adult worms by 100% and 58.3% at 24h post-exposure, respectively. CA caused cuticle and vulvar flap wrinkling and bubbles to emerge from the tegument. Carvacrol caused more discreet effects on the cuticle and vulvar flap. The LD10 and LD50 of CA were 566.7 mg/kg and 1544.5mg/kg, respectively. The LD10 and LD50 of carvacrol were 546.8 mg/kg and 919 mg/kg, respectively. CA and monepantel reduced the epg of sheep by 65.9 and 96.4%, respectively, at 16 days post-treatment. CA showed in vitro and in vivo anthelmintic activity and was less toxic than carvacrol.

Anthelmintic effect of thymol and thymol acetate on sheep gastrointestinal nematodes and their toxicity in mice

“…Carvacryl acetate (CA), a derivate acetylated from carvacrol, presented lower ovicidal activity than the origin compound , providing evidence that acetylation did not potentiate the ovicidal activity of these monoterpenes. Thymol presented ovicidal activity (EC 50 = 0.1 mg/mL) similar to citral (EC 50 = 0.1 mg/ml) and higher than the compounds isolated from essential oils that exhibit anthelmintic activity, such as carvacrol (EC 50 = 0.17 mg/mL), anethol (EC 50 = 0.6 mg/mL), Terp-4-ol (EC 50 = 0.63 mg/mL), borneol (EC 50 = 1.5 mg/mL), and camphor (EC 50 = 1.8 mg/mL) (CAMURÇA-VASCONCELOS et al, 2007;QI et al, 2015;MACEDO et al, 2015;ANDRE et al, 2016). The ovicidal effect of thymol is probably related to the presence of hydroxyl radical in its chemical structure, considering that thymol acetate presented significantly lower results at the EHT.…”

Kazakh Ziziphora Species as Sources of Bioactive Substances

“…carvacryl acetate) (74) Z. tenuior [94] Anthelmintic Haemonchus contortus [371] Anti-inflammatory effect through inhibition of edema induced by carrageenan, histamine, serotonin or PGE 2 [372] Anxiolytic-like effect probably through acting on the GABAergic system [373,374] Z. tenuior [94] Anthelmintic Haemonchus contortus [371] Anti-inflammatory effect through inhibition of edema induced by carrageenan, histamine, serotonin or PGE2 [372] Anxiolytic-like effect probably through acting on the GABAergic system [373,374] O…”

“…trans-Isopiperitenol) (75) Z. tenuior [94] n.f. Z. tenuior [94] Anthelmintic Haemonchus contortus [371] Anti-inflammatory effect through inhibition of edema induced by carrageenan, histamine, serotonin or PGE2 [372] Anxiolytic-like effect probably through acting on the GABAergic system [373,374] O…”

“…cumaldehyde) (78) Z. clinopodioides subsp. rigida (0.8%) [21] Tyrosinase inhibitory activity [377] Suppression of melanin formation in cultured murine B16-F10 melanoma cells [378] O H Z. tenuior [94] Anthelmintic Haemonchus contortus [371] Anti-inflammatory effect through inhibition of edema induced by carrageenan, histamine, serotonin or PGE2 [372] Anxiolytic-like effect probably through acting on the GABAergic system [373,374] O O Antibacterial (multi-drug resistant E. coli) [329] Insecticidal activity (against Lasioderma serricorne) [351] GABAA receptor modulation [322] Repellent activity against Anopheles gambiae [375] Anti-ischemic and anti-inflammatory activity [376] OH trans-Verbenol (77) Z. clinopodioides subsp. rigida (0.1%) [21] Antibacterial (multi-drug resistant E. coli) [329] GABAA receptor modulation [322] OH Cuminyl aldehyde (syn.…”

“…cumaldehyde) (78) Z. clinopodioides subsp. rigida (0.8%) [21] Tyrosinase inhibitory activity [377] Suppression of melanin formation in cultured murine B16-F10 melanoma cells [378] O H Z. clinopodioides (0.12%-0.24%) [15] Ziziphoroside A (79) Z. clinopodioides [4] Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] O O Glc Z. tenuior [94] Anthelmintic Haemonchus contortus [371] Anti-inflammatory effect through inhibition of edema induced by carrageenan, histamine, serotonin or PGE2 [372] Anxiolytic-like effect probably through acting on the GABAergic system [373,374] O…”