Post-treatment with maropitant reduces oxidative stress, endoplasmic reticulum stress and neuroinflammation on peripheral nerve injury in rats.

OBJECTIVE: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: 98 male Wistar rats. METHODS: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant. The effect on inflammatory mediators (IL10, TNFα), oxidative stress (GPx, CAT, SOD), microglial (IBA-1) and neuronal (NeuN, TACR1) markers was evaluated though immunohistochemistry and expression levels of markers of hypoxia (HIF1α, Nrf2), antioxidant enzymes (Catalse, Sod1 and GPx1), and endoplasmic reticulum stress mediators (GRP78, CHOP and PERK) through qRT-PCR. RESULTS: Intraperitoneal injection (IP) of maropitant inhibited nociception with ID50 values of 4,1 mg/kg (5,85-19,36) in a neuropathic pain model through CCI. A dose of 30 mg/kg/24q was significantly effective in reducing mechanical allodynia 1 to 4h after treatment with nociception inhibition (145,83%). A reduction in the expression of hypoxia factors (HIF1α, Nrf2) was observed, along with an increase in antioxidant activity (CAT, SOD and GPX). Additionally, there was a reduction in inflammatory markes (IL10, TNFα), microglial (IBA-1), and neuronal markers (NeuN, TACR1). CONCLUSION AND CLINICAL RELEVANCE: These findings demonstrate that the determined dose, administered daily for seven days, had an antinociceptive effect, as well as anti-inflammatory and antioxidant activity.

The use of tear ferning test in cats for evaluation of ocular surface.

BACKGROUND: The tear film is a trilaminar fluid composed mainly of lipids, electrolytes, proteins and water. It is responsible for lubrication, nutrition and protection against microbial and toxic agents. Disruption of any these components may weaken the ocular surface, making it more susceptible to disease. Increasing evidence suggests that qualitative tear film deficiencies are an important predisposing factor or cause of some of the most common and challenging ocular diseases in cats, including conjunctivitis, corneal ulcer, spontaneous chronic corneal epithelial defects (SCCED), pigmentary keratitis, corneal sequestrum and dry eye syndrome. The aim of this study was to describe the tear ferning test in healthy cats and to compare the results by using two grading scales for humans. Tear samples were collected using Schirmer tear test (STT) strips from 60 healthy cats, and, after centrifuging the strips to obtain the samples, the aliquot was placed on clean microscope glass until it dried and the tear ferning patterns were observed under a polarized light microscope and classified according to the Rolando and Masmali grading scales. RESULTS: Ferning patterns in the lower grades showed full crystallization with high density, without gaps between the ferns and branches, forming several nuclei that were easily distinguished. According to the Rolando scale, 50% (60/120), 46.6% (56/120) and 3.4% (4/120) of eyes showed type I, II and III patterns, respectively. According to the Masmali scale, 15% (18/120), 56.6% (68/120 eyes) and 28.4% (34/120) of eyes showed grade 0, 1 and 2 patterns, respectively. No difference was observed between the right and left eyes for both Rolando (P = 0.225) and Masmali (P = 0.683) scales. CONCLUSIONS: The tear ferning test is a qualitative test that can be used in cats as a complementary evaluation of the ocular surface. While the Rolando scale showed an increased prevalence of types I and II, the Masmali scale showed an increased prevalence of grades 1 and 2. This can be attributed to the species-specific differences between human and feline tear film. So Masmali grade 2 can be considered a normal tear pattern for the species, because all the cats used in study were clinically healthy. For this reason, future complementary studies are necessary for comparing healthy eyes and eyes with different ocular surface disease in cats. Both scales can be feasible options for grading tear crystallization in cats, but as Rolando scale included 96.6% of the samples in the 2 types that are considered normal for humans, we think that this scale seemed to be more precise to classify crystallization pattern in cats. The crystallization patterns observed in this study can form the basis for standardizing ocular surface parameters in cats.