Abstract
In this study we screened various crude fractions of Cannabis sativa indigenous to Pakistan against cisplatin-induced vomiting in pigeon and to find the involvement of gastrointestinal (GIT) motility and gastric emptying in said complication. Cannabis sativa hexane (CS-HexFr 5, 10 and 15 mg/kg), n-butanol (CS-ButFr 5 and 10 mg/kg) and methanol fractions (CS-MetFr 10 and 15 mg/kg) were examined against cisplatin-induced vomiting and their possible effects on GIT motility/gastric emptying in pigeon by charcoal propulsion method. Standard prokinetic drugs metoclopramide (MCP, 30 mg/kg) and carbachol (0.1 mg/kg) were screened in combination with CS-HexFr to estimate the involvement of gastric emptying and GIT motility in cisplatin-induced vomiting. CS-HexFr at the dose of 10 mg/kg once and twice daily attenuated cisplatin-induced vomiting up to 55.45 and 68.86% (P < 0.01), respectively. CS-MetFr and CS-ButFr failed to reduce cisplatin-induced vomiting (P > 0.05). CS-HexFr 10 mg/kg caused up to 26.62% suppression in GIT motility as compared to vehicle treatment group. MCP (30 mg/kg) and carbachol (0.1 mg/kg) completely antagonized the suppression caused by CS-HexFr 10 mg and in combination enhanced the antiemetic profile at 12 to 24 h, while no enhanced activity was observed at 0 to 12 h. The findings suggest that the decrease in GIT motility/gastric emptying is playing a role at least in part in the vomiting induced by cisplatin commencing just after the peak vomiting response of acute phase in pigeon. Key words: Cisplatin, vomiting, gastrointestinal motility, Cannabis sativa, carbachol.
Highlights
Cisplatin is one of the broad spectrum anti-cancer agents indicated for various carcinomas including ovarian, testicular, lungs, head and neck, bladder and breast carcinomas (Jarve and Aggarwal, 1997)
The findings suggest that the decrease in GIT motility/gastric emptying is playing a role at least in part in the vomiting induced by cisplatin commencing just after the peak vomiting response of acute phase in pigeon
Cisplatin at the dose of 7 mg/kg induced vomiting in all of the pigeons tested without lethality with a mean latency, vomiting episodes and jerks of 69 ± 3.7, 44 ± 3.1 and 595 ± 70.0, respectively (Table 1)
Summary
Cisplatin is one of the broad spectrum anti-cancer agents indicated for various carcinomas including ovarian, testicular, lungs, head and neck, bladder and breast carcinomas (Jarve and Aggarwal, 1997). Aside from its useful broad spectrum anti-cancer activity, it has a lot of adverse reactions as well including oxidative stress (Sodhi and Gupta, 1986), lipid peroxidation (Sugihara et al, 1987), hypocalcemia, hypomagnesia (Hodgkinson et al, 2006; Lajer and Daugaard, 1999; Martin et al, 1992), nausea and vomiting (Qiu-hai et al, 2010), ototoxicity (Rybak et al, 2007), stomach distention and nephrotoxicity (Aggarwal et al, 1994). The acute phase last up to 24 h in humans (Tavorath and Hesketh, 1996) and it is mediated by 5HT3 receptors as 5-HT3 receptor antagonists are proving themselves to be effective, while delayed phase last up to several days (Kris et al, 1998) and is poorly controlled even by using combination regimen of currently available antiemetics.
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