The ovaries of ivermectin-resistant Rhipicephalus microplus strains display proteomic adaptations involving the induction of xenobiotic detoxification and structural remodeling mechanisms.

Controlling Rhipicephalus microplus is among the most significant challenges for livestock production worldwide. The indiscriminate use of acaricides stimulates the selection of resistant tick populations and is therefore ineffective. Understanding the molecular foundations of resistance could help inform the search for new alternatives for tick control. Although the ovary has been suggested as a relevant target organ for tick control, there are few existing studies that focus on tick ovarian tissue. Therefore, we conducted a comparative proteomic analysis on ovaries of R. microplus strains with differential resistance to ivermectin. In resistant ticks, we observed the over-accumulation of proteins involved in several biological processes, including translation, proteolysis, transport, cellular organization, differentiation, and xenobiotic detoxification. We also observed the accumulation of many structural and extracellular proteins such as papilin-like protein, which glycosylation increase its stability-based molecular modeling. Therefore, we propose that ovaries of ivermectin-resistant ticks overcome the negative impact of ivermectin through the activation of detoxification mechanisms and structural proteins associated with the remodeling of the ovary's extracellular matrix. SIGNIFICANCE: Understanding the molecular foundation of ivermectin resistance in Rhipicephalus microplus represents an essential step in cattle farming, which could provide clues and alternatives for tick control. Excessive use of chemicals like ivermectin allows the generation of resistant tick strains in different countries. However, limited molecular information is available concerning the tick's resistance to ivermectin. Detailed proteomics scrutiny in various tick organs will provide more comprehensive molecular information. Thus, we conducted an ovary comparative proteomic-based TMT-SPS-MS3 approach. We highlight in ivermectin-resistant ticks the over-accumulation of structural proteins and enzymes connected to detoxification mechanisms.

Comparative proteome analysis of the midgut of Rhipicephalus microplus (Acari: Ixodidae) strains with contrasting resistance to ivermectin reveals the activation of proteins involved in the detoxification metabolism.

Rhipicephalus microplus is the most serious tick parasite for the livestock industry in tropical and subtropical regions. A cost-effective control method to manage the infestation of this parasite involves the use of chemicals such as ivermectin. However, massive overuse of ivermectin over recent decades has selected for ivermectin-resistant populations of R. microplus. Here, we carried out a comparative proteomic analysis of the midgut of ivermectin-susceptible versus ivermectin-resistant ticks using tandem mass tags coupled to synchronous precursor selection. In susceptible ticks, there was an over-representation of proteins associated with blood digestion and anticoagulation. In contrast, resistant ticks exhibited an over-accumulation of proteins involved in phase I and phase II of the detoxification metabolism, including cytochrome P450, glutathione-S-transferase, and ABC transporters, as well as many ribosomal and other translation-related proteins. This information provides new clues about the mechanisms of ivermectin resistance in R. microplus as well as suggesting potential novel molecular targets to cope with ivermectin-resistant populations of R. microplus. SIGNIFICANCE: Cattle farming is an important primary economic activity for food production all over the globe. However, this activity also has detrimental environmental impacts, including the overuse of ivermectin and other chemicals used to control parasite infestations. The overuse of ivermectin selected for parasites with resistance to this chemical, including tick species like R. microplus. There has been extensive to understand the mechanisms that mediate ivermectin resistance in arthropods, but many gaps remain for the full comprehension of this phenomenon. Understanding the biochemistry behind ivermectin resistance could provide new alternatives to fight these parasites. We therefore consider that determining the metabolic mechanisms involved in ivermectin resistance is of great relevance. The comparative proteomic analysis here reported shows the relevance of the active detoxifying metabolism in the midgut of resistant ticks, which may be key for the development of novel control methods.

Effect of Hibiscus sabdariffa on obesity in MSG mice.

The aim of the present investigation was determine whether a standardized Hibiscus sabdariffa calyces aqueous extract has an effect on body weight in an obese animal model induced by the administration of monosodium glutamate. Hibiscus sabdariffa aqueous extract, containing 33.64 mg of total anthocyanins per each 120 mg of extract, was orally administered (120 mg/kg/day) for 60 days to healthy and obese mice, and body weight gain, food and liquid intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and triglycerides levels were measured. Hibiscus sabdariffa administration significantly reduced body weight gain in obese mice and increased liquid intake in healthy and obese mice. ALT levels were significantly increased on the 15th and 45th days in obese mice, but AST levels did not show significant changes. Mortality was not observed in the Hibiscus sabdariffa treated groups. Triglycerides and cholesterol levels showed non-significant reductions in animals treated with Hibiscus sabdariffa. Our data confirm the anti-obesity effect of Hibiscus sabdariffa reported by the Mexican population.