Hydroxychloroquine ameliorates dasatinib-induced liver injury via decrease in hepatic lymphocytes infiltration

Abstract

Dasatinib is an effective treatment for chronic myeloid leukemia. However, cases of idiosyncratic hepatotoxicity were reported. This study was conducted to investigate the chemopreventive effects of hydroxychloroquine against dasatinib-induced hepatotoxicity. Balb/c mice were randomly assigned into four groups; vehicle control (5% DMSO, i.p., n = 6), dasatinib (50 mg/kg; i.p., n = 6), hydroxychloroquine (10 mg/kg, i.p., n = 6), and hydroxychloroquine + dasatinib (10 mg/kg + 50 mg/kg; i.p., n = 6). Treatments were given once every 2 days for 14 days. Serum and histopathological assessments of liver architecture and fibrosis were performed using H&E, Masson’s trichrome, and reticulin staining. The infiltration of lymphocytes was assessed using immunohistochemistry. The gene expression of antioxidant enzymes (CAT, SOD-2, GPX-1) was assessed using real-time quantitative PCR. Dasatinib showed a significant increase in liver injury biomarkers (AST and ALT) with higher lymphocytes infiltration (as indicated by CD3+, CD4+, CD8+, and CD20+ immunohistochemistry). Hepatic tissue of Dasatinib group exhibited significant downregulation in the gene expression of antioxidant enzymes (CAT, SOD-2, and GPX-1) compared to the control group. However, the combination of hydroxychloroquine with dasatinib showed a slight increase in AST and ALT. Also, hydroxychloroquine + dasatinib treated mice showed a significant reduction in lymphocytes infiltration as compared to dasatinib. The results showed that dasatinib induces an immune response leading to an increase in lymphocytes infiltration which promotes hepatocyte destruction and persistent liver injury. The results also suggest that hydroxychloroquine ameliorates dasatinib-induced hepatotoxicity via reduction in hepatic infiltration of T and B immune cells.

Hydroxychloroquine and Zinc ameliorate interleukin-6 associated hepato-renal toxicity induced byAspergillus fumigatusin experimental models

“…Research indicates that IL-6 may substantially impact B cell hyperactivity and could even directly impact tissue harm [23]. However, results show that HCQ was able to ameliorate Aspergillosis-induced hepatoxicity through concomitant reduction of IL-6 levels and decreased polymorphonuclear infiltrates [24]. Although zinc supplement has not been shown to result in higher expression of , the results from this study revealed higher expression of IL-10 when HCQ and zinc are simultaneously administered to experimental models.…”

Hydroxychloroquine and zinc ameliorate interleukin-6 associated hepato-renal toxicity induced by <i>Aspergillus fumigatus</i> in experimental rat models

“…Research indicates that IL-6 may substantially impact B cell hyperactivity and directly impact tissue harm (26). However, other research showed that HCQ was able to ameliorate aspergillosis-induced hepatoxicity through concomitant reduction of IL-6 levels and decreased polymorphonuclear infiltrates (27). Although zinc supplements have not been shown to result in higher expression of IL-10 (28), the results from our study revealed higher expression of IL-10 when HCQ and zinc were simultaneously administered to the experimental rats.…”