*2.1. Blood Meal and the Fate of Heme within Arthropods*

Blood is an excellent source of nutrients, rich in proteins; it also contains the necessary carbohydrates, salts, and lipids that can supply the needs of the arthropod as well as its embryo development [17–20]. Hemoglobin and albumin, the most abundant proteins in the blood, make up almost 80% of the total proteins of blood and are greatly utilized by hematophagous arthropods and blood-dwelling parasites [21]. When hemoglobin is broken down during hematophagy, it results in the liberation of large amounts of heme. Heme itself is capable of promoting the production of ROS [14,22]. In vivo study demonstrates that most of the heme ingested is not absorbed but readily excreted in the feces through several mechanisms. In hemipterans, the lipid membranes in the gut epithelium catalyze the formation of crystalline heme aggregates known as hemozoin. In the mosquitoes, the heme is trapped in the peritrophic matrix of the gut. Ticks, on the other hand, digest blood intracellularly [23–26], wherein the liberated heme is trapped in hemosomes, specialized organelles in tick-gut cells designated to trap the liberated heme [8,22]. Although the gut of hematophagous arthropods efficiently tends to thwart the absorption of heme, a significant amount of heme is retained within and is capable of inducing oxidative damage at the cellular level and causes lipid peroxidation [12,14]. A mechanism to degrade

heme and reduce its toxic effects is also present within vectors. Although seemingly beneficial, it can cause another problem by releasing highly reactive free Fe2+, which may trigger the Fenton reaction, ultimately resulting in accelerated ROS production, and thus, eventually exacerbating oxidative stress [12]. However, this phenomenon is not observed in ticks since they lack the heme oxygenase gene [27]. In sandflies and *Aedes aegypti*, hemoglobin digestion intermediates also induce oxidative stress upon contact with the gut epithelium [16,28]. Iron is also acquired from the serum from the hosts' ferritin, transferrin, and other iron-binding proteins found in the host blood [13].

Hard ticks are pool feeders, and they attach for a long period that can range for 3–12 days depending on the species and developmental stage of life cycle. Interestingly, the attachment period may extend up to 60 days when they attach to a reptile host [3,5,6,29–31]. During feeding, ROS are also generated from the hosts' eosinophils, neutrophils, and macrophages through the lesion brought about by blood feeding [5,30,32,33]. In bloodfeeding arthropods such as mosquitoes and ticks, the control of oxidative stress from heme and iron toxicity, which includes postprandial downregulation of ROS production in insect cells, matrix peritrophins, heme catabolism, and iron chaperones and shuttling, has already been thoroughly discussed in previous works [12,17,22].
