Abstract
Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.
Highlights
Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors
Kidney health was evaluated by examining serum albumin, creatinine, and blood urea nitrogen (BUN)
The ifosfamide control group A and ifosfamide control group B had the mean values of 3.1 ± 0.08 and 3.5 ± 0.4 g/dL, respectively, which were considerably lower than the saline control group
Summary
Ifosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. Many regenerating tissues (gastrointestinal tract mucosa, bone marrow, etc.) possess high proliferating ability and endure the toxic effects of c hemotherapy[3] These factors escalate the morbidity and mortality of cancer treatment. Ifosfamide (3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H1,3,2-oxazaphosphorine 2-oxide) is a nitrogen mustard and belongs to the oxazaphosphorine class It is an alkylating agent with promising potentials in the treatment of various types of cancer, including lymphoma (Hodgkin and non-Hodgkin) and osteosarcoma, as well as, ovarian, testicular, soft tissue, lung, cervical, and breast cancer[4]. Neurotoxicity is the most widely reported of all and occurs in almost 20% of patients with symptoms of severe hallucinations, confusion or somnolence seizures, and c oma[7] These side effects can range from acute to chronic, reversible to irreversible, trifling to potentially fatal, and their management is of extreme importance because they greatly influence the dose and course of treatment[8]. The maximum therapeutic benefits of ifosfamide requisite an antidote that can attenuate its induced toxicities with synergistic improvement in its efficacy as a chemotherapeutic agent
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