Induction of Cyto-pathological Alterations in Body by Captopril

Captopril (Brand name: Capoten) is an angiotensin-converting enzyme inhibitor which is used for the treatment of hyper-tension¹ and congestive heart failure, that's why it is also referred as cardio protective drug².

Scientists have done a research on patients which were treated with Captopril in order to study the histopathological response of liver. It is also suggested that patients treated with Captopril are more likely to suffer with hepatic injury and jaundice³. Therefore, a research was done on rats to check the hepatocytic vaculor degeneration. Rats were treated w ith Captopril at dose of 1000 mg kg^-1 over a 3 months toxicity investigation⁴ and hepatocytic vacuolar degeneration was found in dead rats.

On the other hand, Furosemide is a diuretic drug which is used to treat cardiovascular and renal diseases⁵. It is reported that Furosemide causes liver damage and huge hepatic necrosis in mice because of its diuretic action^6,7.

Therefore, an experiment was conducted in order to evaluate the side effects of Captopril on organs including heart, liver and kidney. The purpose of this experiment was also to assess the role of Furosemide whether it inhibits or promotes the side effects of Captopril⁸.

For this purpose, scientists employed 2 dose levels of Captopril; low dose of 0.01 mg for 6 days a week, for the duration of 4 weeks as well as elevated dose of 0.23 mg for 6 days a week, for 4 weeks. Changes produced by Captopril were found to be statistically proportional to the dose utilized⁸.

Afterwards, another 2 groups were investi- gated. One of these groups was subjected to the low Captopril dose only with Furosemide (0.02 mg) and the other received the high Captopril dose only with the same Furosemide dose for the same period of treatment⁸.

Conclusively, Captopril administration at low and high dose induced cyto-pathological alterations in myocardial tissue, liver as well as kidney at the ultra structural level in tested mice. However, Furosemide was found to restrain both the decrease in body weight and mortality rate induced by the administration of Captopril alone. It is suggested that Furosemide is unable to inihibit the cyto- pathological alterations in mice.

REFERENCES

1. Sultana, N., M.S. Arayne and R. Quraish, 2007. In vitro interactions of captopril with H₂-receptor antagonists. Pak. J. Pharmaceut. Sci., 20: 132-139.
2. Khattab, M.M., A. Mostafa and O. Al-Shabanah, 2005. Effects of captopril on cardiac and renal damage and metabolic alterations in the nitric oxide-deficient hypertensive rat. Kidney Blood Press Res., 28: 243-250.
3. Rahmat, J., R.L. Gelfand, M.G. Gelfand, J.F. Winchester, G.E. Schreiner and H.J. Zimmerman, 1985. Captopril-associated cholestatic jaundice. Ann. Internal Med., 102: 50-56.
4. Takase, K., T. Ikuse, H. Aono and A. Okahara, 1995. Toxicity study of the angiotensin converting enzyme inhibitor rentiapril in rats. Arzneimittelforschung, 45: 15-18.
5. Mitchell, J.R., W.L. Nelson, W.Z. Potter, H.A. Sasame and D.J. Jollow, 1976. Metabolic activation of furosemide to a chemically reactive, hepatotoxic metabolite. J. Pharmacol. Exp. Therapeut., 199: 41-52.
6. Mitchell, J.R., W.Z. Potter, J.R. Hinson and D.J. Jollow, 1974. Hepatic necrosis caused by furosemide. Nature, 251: 508-511.
7. Hufnagle, K., S.N. Khan, D. Penn, A. Cacciarelli and P. Williams, 1982. Renal calcifications: A complication of long-term furosemide therapy in preterm infants. Pediatrics, 70: 360-363.
8. Abdelmeguid, N.E., S.S. Hamed and E.A. Ahmed, 2008. Ultrastructural studies on the effect of captopril and furosemide on some organs of albino swiss mice. Asian J. Cell Biol., 3: 1-21.