Investigation of the protective effect of protocatechuic acid against cisplatin-induced neurotoxicity in rats

Cisplatin is a chemotherapeutic agent widely used in the treatment of various malignant tumors. The aim of this study is to determine the potential protective effects of protocathechic acid, which has mainly antioxidant and anti-inflammatory properties, on the brain in neurotoxicity induced by cisplatin in rats. Forty rats were divided into four groups. 1-Control group: Physiological saline (0.9 %) was given orally for 5 weeks. 2- Protocatechuic acid (PCA) group: Protocatechuic acid was administered orally at a dose of 100 mg / kg / day for 5 weeks. 3-Cisplatin (CIS) group: 5 mg / kg / week of cisplatin was administered intraperiteonally once a week starting from the second week for 5 weeks. 4- Protocatechuic acid + Cisplatin (PCA + CIS) group: The rats were given protocatechuic acid orally (at a dose of 100 mg / kg / day) daily for 5 weeks and additionally, cisplatin i.p. (at a dose of 5 mg / kg / week) once a week starting from the second week. At the end of the experiment, the brain tissues of the animals sacrificed by decaptation were removed from the skull and the brain was divided into two as sagittal. One half was used for histopathological examinations and the other half was used for TAC, TOS, TNF-α, IL-6, IL-1β, acetylcholinesterase, glutamate, GABA, dopamine analyzes in ELISA. WBC, RBC, hemoglobin and hematocrit levels were measured as hematological parameters in the blood with anticoagulants. PCA + CIS group compared to CIS group TOS (p <0.001), TNF-α (p <0.001), IL-6 (p <0.001), IL-1β (p <0.001), acetylcholinesterase (p <0.001), glutamate ( p <0.01), WBC (p <0.001) levels decreased significantly, while TAC (p <0.001) and GABA (p <0.001) levels increased statistically significant. With this study, protocatechuic acid corrected the deterioration in the oxidant / antioxidant status in the brain against cisplatin-induced neurotoxicity, suppressed neuro-inflammation, decreased acetylcholinesterase activity, which increased with neurotoxicity, partially normalized neurotransmitters, and decreased the increased WBC count. Necrosis seen in the CIS group in histopathological examinations was never seen in the PCA + CIS group. As conclusion; protocatechuic acid may provide therapeutic benefit when used in conjunction with cisplatin.