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Indian Journal of Pharmacology, Vol. 36, No. 3, June, 2004, pp. 176-177 Research Letter Histomorphological changes induced by Vitex negundo in albino rats Tandon Vishal, Gupta RK Post Graduate Department of Pharmacology & Therapeutics, GMC, Jammu (J&K) - 180 001 Code Number: ph04059 Sir, Vitex negundo Linn. (VN) has been investigated extensively for its antiinflammatory[1],[2] and analgesic[1],[2] activities but it was only Telang et al (1999)[1] who noticed the inhibitory activity of the extract on prostaglandin biosynthesis and confirmed NSAID-like activity. But the type of cyclooxygenase inhibition produced by the extract is yet to be explored. Moreover, there are only a few studies[2] regarding acute toxicity and very little is known about the histomorphological changes produced in various vital organs by toxic doses of VN. Therefore, the present study was undertaken to evaluate the histomorphological changes produced in various organs and to ascertain the type of cyclooxygenase inhibition produced. The plant VN was collected from the local area of Sevagram, Dist. Wardha, Maharashtra and authenticated by an expert. The fresh leaves were shade-dried and powdered. The powder was macerated for 24 h in 70% v/v ethanol. Then it was subjected to percolation by using 70% v/v ethanol as solvent. The menstrum collected was again shade-dried and dissolved in distilled water to prepare an aqueous solution in the desired concentration just before use. Albino rats of either sex (weight 125-180 g) of Wistar strain were procured from the National Institution of Nutrition, Hyderabad. The study was cleared by the Ethics Committee constituted for the purpose. The animals were housed at 25 ± 2°C in polypropylene cages (4 per cage) with dust-free rice husk as bedding material and were provided with food and water ad libitum and were acclimatized for one week to laboratory conditions. The rats were fasted for 24 h before the experiment. The acute toxicity study was carried out by administering VN leaf extract orally in graded doses (1-10 g/kg, body weight) to seven groups of animals each consisting of six animals. LD50 of the extract was determined by graphical method[3] and the histomorphological changes in vital organs were studied. The rats were observed continuously for two hours, then occasionally for a further four hours for any mortality onset and for the severity of any toxic sign. Finally, overnight mortality was recorded. The specimens of the stomach, liver, heart and lung from animals in which mortality was observed and of those which were sacrificed after 24 h were sent for histopathological examination to the department of pathology. The groups were compared using Z test and a P value <0.05 was considered significant. The results are shown in [Table - 1]. The present study indicated that oral LD50 dose of VN leaf extract is 7.58 g/kg, b.wt of rats. The LD50 falls practically in the non-toxic dose range for a given compound as mentioned by Ghosh (1984).[3] These findings are in agreement with those of Ravishankar et al. (1985).[2] The stomach showed no histomorphological changes in any of the doses of the extract. These findings were contrary to the earlier study which proposed inhibition of prostaglandin biosynthesis.[1] Prostaglandins are known to have cytoprotectant properties which help maintain the integrity of gastric mucosa, and NSAIDs with greater selectivity for COX-2 inhibition have lesser ulcerogenic potential.[4] VN which is known to act by prostaglandin inhibition, may be expected to cause gastric damage but on the contrary it produced no histomorphological changes in the stomach even in toxic doses. This may be due to a selective COX-2 inhibition that might be responsible for the NSAID-like activity.[1] Dose-dependent histomorphological changes were observed in the specimens of the heart, liver and lung. Toxic effect on myocardium was noticed with lower and higher doses. The specimens of the heart appeared thickened and hyperemic grossly, and showed vascular dilatation and hemorrhage significantly (P<0.05) in 2.5 and 5 g/kg, wt. doses and (P<0.01) in 7.5 and 10 g/kg, wt. doses of VN extract, microscopically. istomorphological changes were observed in the liver with intermediate and higher doses. Although the specimens of the liver appeared apparently normal on gross examination, they showed non-specific portal dilatation significantly (P<0.05) in doses of 7.5 and 10 g/kg, wt. of the extract, microscopically. Whereas changes in the lung was observed with a higher dose (10 g/kg, wt.) only. The lungs showed edema and congestion on gross examination and significant (P<0.01) vascular dilatation and congestion microscopically. From the histomorphological examination it seems that the major toxic assault of VN was on the heart. The major cause of mortality seems to be cardiopulmonary arrest as non-reversible severe dyspnoea was noticed mostly after twelve hours of the administration of the extract. This occurred in only those animals from various groups in which mortality was observed. The appearance of dyspnoea could not have been due to lung injury as a toxic change in the lung was seen only in a higher dose of VN extract. Therefore, the dyspnoea is likely to have been caused by cardiac toxicity in the form of vascular dilatation and hemorrhage which seems to be major cause of mortality in the present study. ACKNOWLEDGEMENTS The authors are grateful to Dr. N. Gagnae (Professor, Department of Pathology, MGIMS, Sevagram (Wardha), Maharashtra for helping us to undertake histopathological work in the department for the present study.REFERENCES
Copyright 2004 - Indian Journal of Pharmacology The following images related to this document are available:Photo images[ph04059t1.jpg] |
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