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Dose dependent acute toxicity of abrin in Balb/c mice after intraperitoneal administration

Phatak, Pooja, Nagar, Durga Prasad, Saxena, Nandita
Toxicon 2019 v.167 pp. 49-59
Abrus, abrin, acute toxicity, alanine transaminase, alkaline phosphatase, ammonia, antioxidants, bilirubin, bioterrorism, blood serum, death, dose response, erythrocyte count, hemoglobin, hepatotoxicity, histology, inflammation, interferon-gamma, intraperitoneal injection, lipid peroxidation, liver, mice, neutrophils, oxidative stress, ricin, seeds, tumor necrosis factor-alpha
Abrin toxin is one of the most potent and deadly plant toxin obtained from the seeds of Abrus precatorious. It is more toxic than ricin which is classified as Schedule 1 agent by OPCW and Category B bioterrorism agent by Centre for Disease Control (CDC). Dose dependent acute toxicity of abrin is still a matter of investigation. The present study was carried out to assess the toxicity of abrin from sub lethal to supralethal doses (0.5X, 1X, 2X and 5XLD50) after intraperitoneal administration. After 8 and 24h of abrin exposure, hematological, biochemical, inflammatory and oxidative stress associated parameters were analyzed. Liver histology was also done to analyze the effect of abrin. Abrin exerts its toxicity in a dose and time dependent manner. Increases in neutrophil counts, lipid peroxidation with decreased lymphocyte counts, are the initiating factor irrespective of time and dose. At higher doses of abrin there was a decrease in hemoglobin level and RBC count which is reflected by increased levels of serum ammonia and bilirubin. Neutrophil infiltration in the liver and lipid peroxidation cause liver toxicity (increased production of ALT and ALP); oxidative stress (depletion of GSH and total antioxidant status); inflammation (increased production of TNF-α and IFN-γ). Further, at higher doses of abrin, intensity of oxidative stress, inflammation and liver toxicity are more pronounced which may have been maintained by the self-sustaining loop of toxicity leading to death of the animals.