Abstract
BackgroundSynthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which also possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. In this study, synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period.MethodsEmesis was induced using cisplatin (7.0 mg/kg, i.v). MPG (10, 20, 30 mg/kg), Vit-C (100, 200, 300 mg/kg), GP (50, 100, 150 mg/kg) and BM-ButFr (5, 10, 20 mg/kg) and their combinations were administered i.m., 15 min before cisplatin administration. The number of vomiting bouts, retching, emetic latency and % weight loss were recorded to assess antiemetic potential. Antioxidant activity was evaluated by the DPPH free radical scavenging assay (FRSA).ResultsSignificant attenuation of vomiting bouts, retching, % weight loss along with an increase in latency was produced by all the antioxidants and their combinations compared to cisplatin alone and this is the first report of this activity of GP in pigeons. Low EC50 values in the FRSA for MPG (67.66 μg/mL), Vit-C (69.42 μg/mL), GP (6.498 μg/mL) and BM-ButFr (55.61 μg/mL) compared to BHT standard (98.17 μg/mL) demonstrated their radical scavenging capacity. Correlation between the antioxidant activity and antiemetic efficacy disclosed a high degree of correlation for the tested antioxidants.ConclusionThe selected synthetic and natural antioxidants and their combinations were able to attenuate cisplatin-induced vomiting, which correlated with their potent in vitro antioxidant activity.
Highlights
Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy
Significant reductions in the number of bouts were found with N-(2-mercaptopropionyl) glycine (MPG) [F (3,28) = 10.62, P < 0.0001] (10, 20 mg/kg; 0–8 h, P < 0.001) (Fig. 2a), vitamin C (Vit-C) [F (3,28) = 9.985, P = 0.0001] (100–300 mg/kg; 0–4 h, P < 0.001) (Fig. 2b), grape seed proanthocyanidin (GP) [F (3,28) = 50.97, P < 0.0001] (50–150 mg/kg; 0–8 h, P < 0.001) (Fig. 2c) and Bacopa monnieri n-butanolic fraction (BMButFr) [F (3,28) = 48.28, P < 0.0001] (5–20 mg/kg; 0–8 h and 13–16 h, P < 0.001) (Fig. 2d)
Our results showed that the GP + Vit-C combination yielded an equivalent inhibition of emetic episodes to MPG + Vit-C and BM-ButFr + GP
Summary
Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. Synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period. Nausea and vomiting are the most distressing and commonly occurring side effects of chemotherapeutic agents [1]. Chemotherapy can induce both acute and delayed phases of nausea and vomiting [2]. In pigeons and piglets for instance, the acute phase lasts for 8–16 h while the delayed phase may endure for 48–58 h [3]. In humans, the acute and delayed phases persist for 24 and 7 days, respectively [4].
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