Gallic Acid Attenuates Cardiovascular and Hematological Complications in Vincristine Treatment via Hydroxyl Radical Scavenging and Endogenous Antioxidant Stimulation in Male Wistar Rats

Abstract

The menace of cancer and the nightmare of complications of cancer chemotherapy have driven researchers to explore simple but efficient combination therapy that includes antioxidants, in cancer therapy. The ability of gallic acid to correct the toxic complication of Vincristine was investigated. Twenty adult male rats of the Wistar strain were grouped into four, randomly, consisting of five rats each. The untreated control (group A) was given only distilled water, groups B and C 0.025 mg/kg Vincristine sulfate intraperitoneally once a week for two weeks. Group C rats were thereafter administered 100 mg/kg gallic acid daily by gastric gavage for 14 days. At 14 days, blood pressure and ECG were measured in the rats, then blood samples were obtained via the retrorbital venous plexus for determination of haematological parameters and plasma biochemistry. They were then euthanized through cervical dislocation, under ether anaesthesia, and liver, kidneys, heart, and brain samples were collected, weighed, and stored for determination of marker of oxidative stress in the post mitochondrial fractions of each organ. Results of the study showed that rats in group B had hypertension as evidenced by elevated diastolic and systolic as well as mean arterial pressure while QT interval and corrected QT were slightly elongated. They also had lowered RBC, WBC, and granulocyte counts. Markers of oxidative stress, GSH, and SOD were also depleted while H2O2 generation increased in this group, whereas all the observed anomalies were corrected in the group C rats that were administered both Vincristine and gallic acid. This study further showed that Vincristine, at normal recommended therapeutic dosage is toxic, causing anaemia, panleucopenia, and cardiovascular anomalies via oxidative stress and generation of hydroxyl radicals. These were however corrected by concurrent administration of gallic acid