As shown in Fig. 6C and D, there was an increase in the oxidative damage score after incubation with Fpg and Endo III, indicating the presence of oxidized purines and pyrimidines. As the levels of ordinary and oxidatively generated DNA adducts were similar (mainly between 6 and 12 h), the majority of the DNA damage observed in the kidneys was likely due to oxidative insult (Fig. 6B–D). Since the administration of antilonomic serum (ALS) is the only specific
treatment actually available for L. obliqua envenomation, we decided to test its efficacy in neutralizing biochemical and coagulation abnormalities using our experimental model. For this purpose, ALS was intravenously administered at 2 or 6 h post-LOBE injection (1 mg/kg, s.c.). After 24 h of envenomation, different biochemical Fluorouracil nmr markers and coagulation parameters were determined ( Table 3). Generally, treatment with ALS is able to neutralize LOBE-induced biochemical alterations only if administered within the first 2 h of envenomation.
For example, animals treated with ALS at 2 h had a decrease of 3.6- and 2.5-fold in the levels of serum creatinine and urea, respectively, when compared with the group treated 6 h after LOBE injection. In addition, both the creatinine and urea levels of the envenomed animals that had been treated at 2 h with ALS were not significantly different from the values observed Duvelisib purchase in non-envenomed rats that had been treated with PBS or ALS, indicating Morin Hydrate that these levels had returned
to control values. Similar results were obtained for other parameters, such as CK, CK-MB, AST and ALT, which became normalized only in envenomed rats that had received ALS within the first 2 h. Likewise, plasma hemoglobin levels were also decreased in envenomed rats when ALS was injected at 2 h. However, this reduction was not statistically significant in comparison to envenomed animals that had been treated with PBS instead of ALS. Thus, ALS was not able to completely reverse intravascular hemolysis, even if given early after envenomation. As expected, envenomed animals that were treated with PBS developed consumptive coagulopathy, with lower levels of fibrinogen and prolonged activated partial thromboplastin time (Table 3). In this case, the treatment with ALS both at 2 or 6 h after venom injection normalized the coagulation parameters. The macroscopic and histological signs of hemorrhage were also absent in the envenomed groups that had received ALS injections at 2 or 6 h (results not shown). In the present study, we used an experimental model in rats to investigate the acute physiopathological effects of L. obliqua venom. This model allowed for the broad characterization of venom-induced tissue damage, including biochemical, hematological, histopathological, myotoxic, cardiotoxic and genotoxic alterations.