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Effect of Policosanol on Carbon Tetrachloride-Induced Acute Liver Damage in Sprague-Dawley Rats

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Abstract

Background: Policosanol is a cholesterol-lowering drug purified from sugarcane (Saccharum officinarum, L.) wax. Beneficial pleiotropic effects of policosanol, such as inhibition of the susceptibility of low density lipoprotein to lipid peroxidation, have been shown. Policosanol has a good safety profile and well tolerated and, to date, no drug-related adverse effects have been demonstrated. Specifically, policosanol has not been shown to affect liver function or to increase liver enzyme levels in experimental or clinical studies.

Aim: This study was conducted to determine whether policosanol prevents liver damage induced by carbon tetrachloride (CCl4) in rats, since this model has been associated with an increased rate of lipid peroxidation.

Methods: Male Sprague-Dawley rats were randomised to four experimental groups: negative controls (no CCl4 or policosanol, group 1); positive controls (CCl4 but no policosanol, group 2); policosanol 25 mg/kg (group 3) and policosanol 100 mg/kg (group 4). Acute liver injury was induced in groups 2, 3 and 4 by CCl4 suspended in olive oil and administered at a dose of 1590 mg/kg via intraperitoneal injection. Eighteen hours after CCl4 dosing, the rats were anaesthetised and their livers removed for histopathological studies.

Results: Policosanol 25 and 100 mg/kg dose dependently and significantly (p < 0.01) decreased the percentage of ballooned cells and hepatocytes with lipid inclusions and increased the percentage of normal hepatocytes compared with positive controls. The percentage inhibition of the occurrence of ballooned cells and hepatocytes with lipids was marked, reaching 71 and 49%, respectively, with the higher dose (100 mg/kg). The percentage of swollen hepatocytes was unchanged by policosanol compared with positive controls. No histological alterations in liver sections were found in the negative control group. Necrotic areas and inflammatory infiltrates were observed in the liver of seven of eight (87.5%) animals in the positive control group. However, only one of eight (12.5%) animals treated with policosanol 25 mg/kg and none (0%) treated with the higher dose (100 mg/kg) showed such a pattern.

Conclusions: Policosanol protected against the histological changes characteristic of CCl4-induced hepatic injury in rats, a model of hepatotoxicity in which the process of lipid peroxidation plays a role. Further studies aimed at demonstrating the connection between such hepatoprotective and antioxidant effects of policosanol must be initiated.

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References

  1. Plaa GL, Hewitt WR. Detection and evaluation of chemically induced liver injury. In: Wallace Hayes A, editor. Principles and methods of toxicology. 2nd ed. 1989; New York, Raven Press, Ltd: 599–628

    Google Scholar 

  2. Recknagel RO, Glende EA, Waller RL, Lowry K. Lipid peroxidation: biochemistry, measurement, and significance in liver cell injury. In: Plaa G, Hewitt WR, editors. Toxicology of the liver. New York: Raven Press, 1982: 213–241

    Google Scholar 

  3. Wendel A. Measurement of in vivo lipid peroxidation and toxicological significance. Free Radic Biol Med 1987; 3: 355–8

    Article  PubMed  CAS  Google Scholar 

  4. Menéndez R, Fraga V, Sotolongo V, et al. Efecto de la administración oral del policosanol sobre el metabolismo lipídico de ratas normocolesterolémicas. Rev Mex Cien Farm 1993; 24: 16–8

    Google Scholar 

  5. Menéndez R, Fernández SI, Del Rio A, et al. Policosanol inhibits cholesterol biosynthesis and enhances LDL processing in cultured human fibroblasts. Biol Res 1994; 27: 199–203

    Article  PubMed  Google Scholar 

  6. Menéndez R, Arruzazabala ML, Más R, et al. Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolemia induced by a wheat starch-casein diet. Br J Nutr 1997; 77: 923–32

    Article  PubMed  Google Scholar 

  7. Menéndez R, Amor A, Rodeiro I, et al. Policosanol modulates HMGCoA reductase activity in cultured fibroblasts. Arch Med Res 2001; 32: 8–12

    Article  PubMed  Google Scholar 

  8. Castaño G, Canetti M, Morera M, et al. Efficacy and tolerability of policosanol in elderly patients with type II hypercholesterolemia: a 12 months study. Curr Ther Res 1993; 56: 819–28

    Article  Google Scholar 

  9. Pons P, Rodríguez M, Robaina C, et al. Effects of successive dose increases of policosanol on the lipid profile of patients with type II hypercholesterolemia and tolerability to treatment. Int J Clin Pharmacol Res 1994; XIV: 27–33

    Google Scholar 

  10. Aneiros E, Más R, Calderón B, et al. Effect of policosanol in lowering-cholesterol levels in patients with type II hypercholesterolemia. Curr Ther Res 1995; 56: 176–82

    Article  Google Scholar 

  11. Canetti M, Morera M, Illnait J, et al. One year study on the effect of policosanol (5mg-twice-a-day) on lipid profile in patients with type II hypercholesterolemia. Adv Ther 1995; 12: 245–54

    Google Scholar 

  12. Castaño G, Tula L, Canetti M, et al. Effects of policosanol in hypertensive patients with type II hypercholesterolemia. Curr Ther Res 1996; 57: 691–9

    Article  Google Scholar 

  13. Zardoya R, Tula L, Castaño G, et al. Effects of policosanol on hypercholesterolemic patients with disturbances on serum biochemical indicators of hepatic function. Curr Ther Res 1996; 57: 568–77

    Article  CAS  Google Scholar 

  14. Ortensi G, Gladstein H, Valli H, et al. A comparative study of policosanol versus simvastatin in elderly patients with hypercholesterolemia. Curr Ther Res 1997; 58: 390–401

    Article  CAS  Google Scholar 

  15. Canetti M, Morera MS, Más R, et al. Effects of policosanol on primary hypercholesterolemia: a 3 year open follow-up. Curr Ther Res 1997; 58: 868–75

    Article  CAS  Google Scholar 

  16. Más R, Castaño G, Illnait J, et al. Effects of policosanol on patients with type II hypercholesterolemia and additional coronary risk factors. Clin Pharmacol Ther 1999; 65: 439–47

    Article  PubMed  Google Scholar 

  17. Castaño G, Más R, Fernández JC, et al. A long-term open study of the efficacy and tolerability of policosanol in patients with high global coronary risk. Curr Ther Res 1999; 60: 379–91

    Article  Google Scholar 

  18. Castaño G, Más R, Arruzazabala ML, et al. Effects of policosanol, pravastatin on lipid profile, platelet aggregation, endothelemia in older hypercholesterolemic patients. Int J Clin Pharm Res 1999; 19: 105–16

    Google Scholar 

  19. Castaño G, Más R, Fernández JC, et al. Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk. J Gerontol A Biol Sci Med Sci 2001; 56: M186–92

    Article  PubMed  Google Scholar 

  20. Torres O, Agramonte AJ, Illnait J, et al. Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care 1995; 18: 393–7

    Article  PubMed  CAS  Google Scholar 

  21. Crespo N, Alvarez R, Más R, et al. Effect of policosanol on patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia: a pilot study. Curr Ther Res 1997; 58: 44–51

    Article  CAS  Google Scholar 

  22. Crespo N, Illnait J, Mas R, et al. Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and non insulin dependent diabetes mellitus. Int J Clin Pharmacol Res 1999; 19: 105–16

    Google Scholar 

  23. Mas R. Policosanol. Drugs Fut 2000; 25: 569–86

    Article  CAS  Google Scholar 

  24. Arruzazabala ML, Carbajal D, Más R, et al. Effects of policosanol on platelet aggregation in rats. Thromb Res 1993; 69: 321–7

    Article  PubMed  CAS  Google Scholar 

  25. Arruzazabala ML, Carbajal D, Molina V, et al. Effect of policosanol on cerebral ischemia in mongolian gerbils: role of prostacyclin and thromboxane A2. Prostaglandins Leukot Essent Fatty Acids 1993; 49: 695–7

    Article  PubMed  CAS  Google Scholar 

  26. Carbajal D, Arruzazabala ML, Valdés S, et al. Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers. Prostaglandins Leukot Essent Fatty Acids 1998; 58: 61–4

    Article  PubMed  CAS  Google Scholar 

  27. Menéndez R, Fraga V, Amor AM, et al. Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation. Physiol Behav 1999; 67: 1–7

    Article  PubMed  Google Scholar 

  28. Menéndez R, Más R, Amor AM, et al. Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro. Br J Clin Pharmacol 2000; 50: 225–62

    Google Scholar 

  29. Menéndez R, Más R, Amor A, et al. Effects of policosanol on the low density lipoprotein (LDL) isolated on hypercholesterolemic patients at high coronary risk to in vitro copper-mediated lipid peroxidation: a randomised, doubleblinded pilot study. Curr Ther Res 2000; 61: 609–20

    Article  Google Scholar 

  30. Alemán CL, Más R, Hernández C, et al. Acute, subchronic and chronic toxicity of policosanol in rats [abstract]. Toxicol Lett 1992; 2: 248

    Google Scholar 

  31. Alemán C, Más R, Hernández C, et al. A 12 months study of policosanol oral toxicity in Sprague-Dawley rats. Toxicol Lett 1994; 70: 77–87

    Article  PubMed  Google Scholar 

  32. Gámez R, Alemán CL, Mas R, et al. A 6-month study on the toxicity of high doses of policosanol orally administered to Sprague-Dawley rats. J Med Food 2001; 4: 57–66

    Article  PubMed  Google Scholar 

  33. Alemán CL, Más R, Noa M, et al. Carcinogenicity of policosanol in Sprague Dawley rats: a 24 month study. Teratog Carcinog Mutag 1994; 14: 239–49

    Article  Google Scholar 

  34. Alemán C, Puig MN, Elías EC, et al. Carcinogenicity of policosanol in mice: an 18-month study. Food Chem Toxicol 1995; 33: 573–8

    Article  PubMed  Google Scholar 

  35. Coro RM, Borrajero I. DIGIPAT. Un sistema cubano para morfometría de imágenes. Rev Latinoam Patol 1996; 39: 9–10

    Google Scholar 

  36. Charbonneau M, Iijima M, Coté MG, et al. Temporal analysis of rat liver injury following potentiation of carbon tetrachloride hepatotoxicity with ketonic or ketogenic compounds. Toxicology 1985; 32: 95–112

    Article  Google Scholar 

  37. Martínez-Calva A, Campos-Apáez E, Rosales-Vega E, et al. Vitamin E improves membrane lipid alterations induced by CCl4 intoxication. J Appl Toxicol 1984; 4: 270–2

    Article  PubMed  Google Scholar 

  38. Muriel P, Mourelle M. Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J Appl Toxicol 1990; 10: 275–9

    Article  PubMed  CAS  Google Scholar 

  39. Rodeiro I, Alemán CL, Más R, et al. Efectos del policosanol sobre las enzimas microsomales hepáticas en ratas S.D. Revista CENIC Cien Biol 2000; 31: 113–6

    CAS  Google Scholar 

  40. Pérez-Souto N, Acosta PC, Mederos CM, et al. Efecto del policosanol sobre la famacocinética de la antipirina. Rev CENIC Cien Biol 1991; 22: 77–8

    Google Scholar 

  41. Nagai H, Aoki M, Shimazawa T, et al. Effect of Oky-046 and ONO-3708 on liver injury in mice. Jpn J Pharmacol 1989; 51: 191–7

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was sponsored through a research grant approved by the Scientific Technical Council of the Havana City West Scientific Organization.

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Correspondence to Miriam Noa.

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Noa, M., Mendoza, S., Más, R. et al. Effect of Policosanol on Carbon Tetrachloride-Induced Acute Liver Damage in Sprague-Dawley Rats. Drugs in R&D 4, 29–35 (2003). https://doi.org/10.2165/00126839-200304010-00003

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