Effects of Mikania glomerata Leaf Extract on Experimental Bothropoides jararaca Envenomation in Wistar Rats

Abstract

Background: Bothropic envenomation represents the most common ophidic accident worldwide, compared to other snakebites of medical interest. Bothropic venom has proteolytic, vasculotoxic, clotting and/or hemorrhagic actions in animals and humans. Mikania glomerata is a plant found in the Brazilian Atlantic Forest with interesting medical properties that may be useful in ameliorating the effects of ophidic venom, and thus, improving response and outcome. Although Mikania is known to act through inhibition of cytolysins in the venom, there is a lack of consistent research data. The aim of this study was to evaluate the effect of M. glomerata in bothropic envenomation treatment. Materials, Methods & Results: Clinical, hematological, biochemical, and histopathological evaluations were performed following Bothropoides jararaca experimental envenomation in three groups of 18 Wistar rats each. Group VS was inoculated in the pelvic limb via intramuscular injection of bothropic venom and received specific anti-venom serum via intraperitoneal injection. Group VSM was similarly inoculated; it received anti-venom serum and a 10% aqueous extract of the Mikania glomerata plant orally. Group C was the control group and received saline solution alone. Evaluations were performed at 0.5 h (M1), 6 h (M2), and 24 h (M3) after venom inoculation. Animals from both inoculated groups (VS and VSM) showed significant clinical alterations (P < 0.05) manifested as discomfort, uneasiness, pain, and severe edema compared to control animals. Animals from inoculated groups also exhibited statistically significant leukocytosis with neutrophilia, and elevation of blood urea nitrogen and creatine kinase until 6 h after inoculation (P < 0.05 compared to control animals). An acute drop in body temperature was observed 6 h after inoculation (P < 0.05). High levels of creatinine were observed at 6 and 24 h, and plasma protein reduction at almost all evaluation time points (P < 0.05) in both groups compared to that in control. Histopathological evaluation of venom-inoculated animals (groups VS and VSM) showed significant renal hydropic degeneration, acute tubular necrosis, congestion, and hemorrhage (P < 0.05 compared to control). In contrast, animals administered plant extract in addition to anti-venom (group VSM) showed milder muscular fiber regeneration and absence of hemorrhage in the inoculated limb, compared to those that received anti-venom alone (group VS). Overall, there were no statistically significant differences between the inoculated groups (P > 0.05) in terms of edema reduction, pain relief, hematological, biochemical, or histopathological alterations. Discussion: Clinical envenomation symptoms can be explained based on previous reports of bothropic events, where cytolysins such as hyaluronidase, phospholipase A2, and esterases are associated with alterations in cell membrane permeability and release of vasoactive agents. Rhabdomyolysis and muscular necrosis are the main causes of muscular and renal alterations in inoculated grou...

Creolin® administered by different pathways in rats experimentally poisoned with Bothrops jararaca venom

“…The extremity of the limb was not affected. This change persisted until the end of the clinical evaluation (hour eight), corroborating the local effects reported in the natural and experimental cases of bothropic venom inoculation in animals (YAMASHITA, 2013;GOMES et al, 2016;MOTTA et al, 2017). The animals of the imC and imBj + C groups did not present hemorrhagic or necrotic changes, only progressive edema of the inoculated region until the end of the evaluation.…”

“…With regard to the hematological findings, there was a significant difference in the leukocyte values of the groups that received the bothropic venom and treatment when compared to those of Control and Bj groups (Table 3); these results corroborate those from the studies on the hematological effects of the bothropic venom, which also demonstrated leukocytosis (MOTTA et al, 2017). Control: sterile saline solution; Bj: only intramuscular bothropic venom; imC: only intramuscular Creolin ® ; Bj+voC: bothropic venom followed by oral Creolin ® treatment; Bj+vtC: bothropic venom followed by topical Creolin ® treatment; Bj+imC: bothropic venom and followed by intramuscular injection of Creolin ® ; imBj+C:intramuscular injection ofa mixture of Creolin ® and bothropic venom.…”

“…The thrombocytopenia caused by the venom is temporary, yet its action on the mechanisms that involve aggregation is lingering (SANTORO et al, 2004;YAMASHITA, 2013). In this experiment, the animals that had contact with the venom and were treated with Creolin ® had a significantly lower platelet count when compared to the values of the Control, imC and imBj+C groups (Table 3), in addition to the presence of aggregation in all samples, similar to the effects of bothropic venom reported in the literature (MOTTA et al, 2017).…”

“…After inoculation (hour zero), the animals were evaluated clinically at each hour for eight hours (hour eight) by adapting the evaluation model used by MOTTA et al (2017). After the end of the clinical evaluation, all animals were anesthetized with a mixture of xylazine (10 mg/kg) and ketamine (75 mg/kg) intraperitoneally and blood samples were collected by cardiocentesis, as advocated by CONCEA (2015).…”

“…Therefore, several substances of animal, vegetal, or mineral origin are commonly used as antiophidics, in an attempt to deliver alternative treatments of low cost that can effectively reverse the symptomatology caused by the venom (GOMES et al, 2016;MOTTA et al, 2017).…”