Safety studies of Nexrutine, bark extract of Phellodendron amurense through repeated oral exposure to rats for 28 days.

Nexrutine (NX), a marketable herbal extract from a traditional Chinese herbal plant, Phellodendron amurense, is majorly used for the resolution of inflammation, gastroenteritis, and some tissue-specific cancer. Strategies for the identification of the safety of anticancer solutions of plant origin are an important area of study. The present investigation assesses the single and repeated dose (28 days) toxicity of NX following OECD guidelines 425 and 407, respectively. Briefly, to identify acute toxic properties of NX, a dose of 2000 mg/kg b. wt was administered once orally. Simultaneously, repeated dose toxicity was evaluated through daily administration of the three different doses (250, 500, 750 mg/kg b. wt) of NX for 28days. The single administration of NX showed no signs of toxicity and morbidity, suggesting LD50 of NX more than 2000 mg/kg b. wt. Furthermore, repeated dose exposure of NX for 28 days did not show any sign of toxicity. Hematology, serum biochemistry, and histopathological analysis also did not show any significant abnormalities. However, a marginal decrease in triglyceride, cholesterol, and glucose levels along with mild tubular degeneration in the kidney was also noticed in the high dose NX treatment group. Overall, the findings of the study suggest that NX is safe for use up to 500 mg/kg b.wt.

Argemone oil, an edible oil adulterant, induces systemic immunosuppression in Balb/c mice in an oral 28 days repeated dose toxicity study.

Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2). At the functional level, AO exposure significantly abrogated the mixed lymphocyte reaction and mitogen-stimulated lymphoproliferative activity of T and B cells, which is reflective of profound lymphocyte dysfunction upon antigen exposure. In concordance with the loss in functional activity of lymphocytes in AO exposed animals, it was found the AO altered the relative percentage of CD3+, CD4+, and CD28 + T cells. Further, there was a marked decrease in the relative distribution of cells with prominent MHC I and CD1d expression in AO exposed splenocytes. Moreover, reduced levels of immune stimulatory cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-6), and increased levels of immunosuppressive cytokine IL-10 were detected in the serum of AO treated mice. Along with T and B cells, AO exposure also affected the phenotype and activation status of macrophages suggesting the inclination towards "alternative activation of macrophages". Altogether, these functional changes in the immune cells are contributing factors in AO induced immunosuppression.

Evaluation and physiological correlation of plasma proteomic fingerprints for deltamethrin-induced hepatotoxicity in Wistar rats.

AIMS: Uprising reports towards deltamethrin (DLM)-induced toxicity in non-target species including mammals have raised a worldwide concern. Moreover, in the absence of any identified marker, the prediction of DLM elicited early toxic manifestations in non-targets remains elusive. MAIN METHODS: Comprehensive approach of proteome profiling along with conventional toxico-physiological correlation analysis was performed to classify novel protein based markers in the plasma of DLM exposed Wistar rats. Animals were exposed orally to DLM (low dose: 2.56mg/kg b.wt. and high dose: 5.12mg/kg b.wt.) up to seven consecutive days. KEY FINDINGS: The UPLC-MS/MS analysis revealed a dose-dependent dissemination of DLM and its primary metabolite (3-Phenoxy benzoic acid) in rat plasma. Through 2-DE-MS/MS plasma profiling and subsequent verification at the transcriptional level, we found that 6 liver emanated acute phase proteins (Apolipoprotein-AIV, Apolipoprotein E, Haptoglobin, Hemopexin, Vitamin D Binding protein, and Fibrinogen gamma chain) were significantly (p<0.05) modulated in DLM treated groups in a dose-dependent manner. Accordingly, DLM exposure resulted in adverse effects on body growth (body weight & relative organ weight), serum profile, liver function and histology, inflammatory changes (enhanced TNF-ɑ, TGF-ß and IL6 level), and oxidative stress. Moreover, these toxic manifestations were suppressed upon N-acetyl cysteine (NAC) supplementation in DLM treated animals. Thus, DLM-induced inflammatory response and subsequent oxidative injury to liver grounds the altered expression of identified acute phase proteins. SIGNIFICANCE: In conclusion, we proposed these six liver emanated plasma proteins as novel candidate markers to assess the early DLM-induced hepatotoxicity in non-target species with a minimal invasive mean.