Abstract
Cytarabine, an anti-metabolite drug, remains the mainstay of treatment for hematological malignancies. It causes various toxic effects including teratogenicity. Alpha lipoic acid (ALA) is a natural antioxidant reported to offer protection against hepatotoxicity induced by various pathological conditions, drugs, or chemicals. We investigated the protective effect of ALA against prenatal cytarabine exposure-induced hepatotoxicity in rat female neonates. A total of 30 dams were randomly assigned to five groups and received normal saline, ALA 200 mg/kg, cytarabine 12.5 mg/kg, cytarabine 25 mg/kg, and cytarabine 25 mg/kg + ALA 200 mg/kg, respectively, from gestational day (GD)8 to GD21. Cytarabine and ALA were administered via intraperitoneal and oral (gavage) routes, respectively. On postnatal day (PND)1, all the live female neonates (pups) were collected and weighed. The blood and liver from pups were carefully collected and used for histopathological, and biochemical evaluations. A significant and dose-dependent decrease in maternal food intake and weight gain was observed in the pregnant rats (dams) of the cytarabine groups as compared to the dams of the control group. The pups exposed to cytarabine showed a significant and dose-dependent (a) decrease in body weight, liver weight, hepatosomatic index, catalase, superoxide dismutase, glutathione, glutathione peroxidase, serum albumin levels and (b) increase in malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, AST/ALT ratio, and histopathological anomalies. Maternal co-administration of ALA ameliorated these biochemical changes and histopathological abnormalities by combating oxidative stress. Future studies are warranted to explore the molecular mechanisms involved in the ALA’s protective effects against prenatal cytarabine-induced hepatotoxicity.
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We would like to acknowledge Bhaskar Medical College, Hyderabad, and Bhaskar Pharmacy College, Hyderabad, for providing facilities and Vivo Bio Tech Ltd., Pregnapur, Telangana, for the support in technological aspects.
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RN and KNC were involved in conceiving the concept and designing the study; analyzing and interpreting data; reviewing and editing of manuscript; and approval of the manuscript. RN contributed to the literature search, carried out the experiment, and wrote the manuscript. KNC supervised the study. Both authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Namoju, R., Chilaka, K.N. Protective effect of alpha‑lipoic acid against in utero cytarabine exposure-induced hepatotoxicity in rat female neonates. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03036-4
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DOI: https://doi.org/10.1007/s00210-024-03036-4