Impacts of graded doses of pyridoxine on the biomarkers, aspartate aminotransferase, lactate dehydrogenase and total antioxidant capacity in doxorubicin-induced cardiotoxicity in female rats

Abstract EN

Doxorubicin (DOX), one of the anthracycline family; most widely used antineoplastic drugs and highly effective in treating cancer patients.

The intended drug exerted its activity mainly by intercalation with DNA and by this means it inducing damage to the DNA and inhibiting the synthesis of macromolecules that are essential to maintain cell life but their use associated with cardiotoxicity adverse effect.

Pyridoxine (vitamin B6) is one of the water soluble B vitamins; converted into the active form, pyridoxal 5’-phosphate (PLP).

Pyridoxine may have a crucial role in antioxidant mechanism.

The aim of the current study was to investigate the possible protective effect of graded doses (5, 10, and 15mg/kg) of pyridoxine hydrochloride intraperitoneally (IP) injected for four consecutive days against single dose of (15mg/kg) doxorubicin-induced cardiotoxicity in female rats IP injected at the fourth day only.

Fifty-six (56) Wistar albino female rats were utilized weighing 180-200 gm allocated into eight groups, seven rats each; and by utilizing IP injection as route of administration as follows: Group I: distilled water (negative control); Group II: Pyridoxine (5mg/kg); Group III: Pyridoxine (10mg/kg); Group IV: Pyridoxine (15mg/kg); Group V: Doxorubicin (15 mg/kg); Group VI: Pyridoxine (5 mg/kg) prior to doxorubicin (15 mg/kg); Group VII: Pyridoxine (10 mg/kg) prior to doxorubicin (15 mg/kg); Group VIII: Pyridoxine (15 mg/kg) prior to doxorubicin (15 mg/kg).

At the 5th day (after 24 hr from the last treatment), blood was withdrawn and heart tissue homogenate obtained for laboratory evaluation.

DOX caused significant elevations in serum biomarker enzymes of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and significant reduction in heart tissue homogenate content of total antioxidants capacity (TAC).

Treatment with 5mg/kg pyridoxine for four consecutive days prior to a single dose 15mg/kg doxorubicin resulted in a non-significant differences in serum enzymes level of AST, LDH, and TAC heart tissue homogenate contents.

Besides, treatment with 10 or 15mg/kg pyridoxine for four consecutive days prior to a single dose of doxorubicin produced significant increments in TAC heart tissue homogenate level compared to positive control.

Moreover, treatment with 15mg/kg pyridoxine for four consecutive days prior to a single dose 15mg/kg doxorubicin resulted in significant reduction in serum enzymes level of AST and LDH.

In conclusion, pyridoxine supplementation might be a promising adjunctive agent for improving oxidative stress and biological markers for preventing DOX-induced cardiac complications.