Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

British Journal of Pharmacology

Volumn 162, Issue 7, 2011, Pages 1650-1658

  Avraham, Y ^a   Grigoriadis, N C ^b   Poutahidis, T ^c   Vorobiev, L ^a   Magen, I ^a   Ilan, Y ^d   Mechoulam, R ^e   Berry, E M ^a  

^a HEBREW UNIVERSITY   (Israel)

^b AHEPA UNIVERSITY HOSPITAL   (Greece)

^c ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^d HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^e HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

cannabidiol; cognition; hepatic encephalopathy; liver enzymes; thioacetamide

Indexed keywords

ALANINE AMINOTRANSFERASE; AMMONIA; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; CANNABIDIOL; SEROTONIN 1A RECEPTOR; SODIUM CHLORIDE; THIOACETAMIDE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; AMMONIA BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; BRAIN FUNCTION; COGNITION; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; FULMINANT HEPATIC FAILURE; HEPATIC ENCEPHALOPATHY; HISTOPATHOLOGY; LIVER FUNCTION; MOTOR ACTIVITY; MOUSE; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; SEROTONIN BLOOD LEVEL; SINGLE DRUG DOSE;

AMMONIA; ANIMALS; BILIRUBIN; BRAIN; CANNABIDIOL; COGNITION; FEMALE; HEPATIC ENCEPHALOPATHY; LIVER; LIVER FAILURE, ACUTE; MICE; MOTOR ACTIVITY; RANDOM ALLOCATION; RECEPTORS, SEROTONIN; THIOACETAMIDE;

EID: 79952378224     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.01179.x     Document Type: Article

References (45)

1. Albrecht J, Hilgier W, Januszewski S, Quack G, (1996). Contrasting effects of thioacetamide-induced liver damage on the brain uptake indices of ornithine, arginine and lysine: modulation by treatment with ornithine aspartate. Metab Brain Dis 11: 229-237. (Pubitemid 126738977)
2. rd edition (2008 revision). Br J Pharmacol 153 (Suppl. 2): S1-S209.
3. Avraham Y, Israeli E, Gabbay E, Okun A, Zolotarev O, Silberman I, et al. (2006). Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol Dis 21: 237-245. (Pubitemid 41817322)
4. Avraham Y, Zolotarev O, Grigoriadis NC, Poutahidis T, Magen I, Vorobiav L, et al. (2008a). Cannabinoids and Capsaicin improve liver function following Thioacetamide-induced acute injury in mice. Am J Gastroenterol 103: 3047-3056.
5. Avraham Y, Magen I, Zolotarev O, Vorobiav L, Pappo O, Ilan Y, et al. (2008b). 2-arachidonoylglycerol, an endogenous cannabinoid receptor agonist, in various rat tissues during the eveloution of experimental cholestatic liver disease. Prostaglandins Leukot Essent Fatty Acids 79: 35-40.
6. Avraham Y, Grigoriadis N, Pautahidis T, Magen I, Vorobiav L, Zolotarev O, et al. (2009). Capsaicin affects brain function in a model of hepatic encephalopathy associated with fulminant hepatic failure in mice. Br J Pharmacol 158: 896-906.
7. Ben-Shabat S, Hanuš LO, Katzavian G, Gallily R, (2006). New cannabidiol derivatives: synthesis, binding to cannabinoid receptor, and evaluation of their antiinflammatory activity. J Med Chem 49: 1113-1117. (Pubitemid 43221657)
8. Butterworth RF, (2010). Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy. Neurochem Int 57: 383-388.
9. Carrier EJ, Auchampach JA, Hillard CJ, (2006). Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci USA 103: 7895-7900.
10. Cauli O, Rodrigo R, Piedrafita B, Llansola M, Mansouri MT, Felipo V, et al. (2009). Neuroinflammation contributes to hypokinesia in rats with hepatic encephalopathy: ibuprofen restores its motor activity. J Neurosci Res 87: 1369-1374.
11. Chen Y, Constantini S, Trembovler V, Weinstock M, Shohami E, (1996). An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J Neurotrauma 13: 557-568. (Pubitemid 26377854)
12. Durst R, Danenberg H, Gallily R, Mechoulam R, Meir K, Grad E, et al. (2007). Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Physiol 293: H3602-H3607. (Pubitemid 350230905)
13. Ferenci P, (1995). Hepatic encephalopathy. In:, Haubrich WS, Schaffner F, Berk JE, (eds). Bockus Gastroenterology, 5th edn. WB Saunders: Philadelphia, PA, pp. 1998-2003.
14. Fernández-Martínez A, Callejas NA, Casado M, Boscá L, Martín-Sanz P, (2004). Thioacetamide-induced liver regeneration involves the expression of cyclooxygenase 2 and nitric oxide synthase 2 in hepatocytes. J Hepatol 40: 963-970. (Pubitemid 38670130)
15. Fride E, Mechoulam R, (1993). Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol 231: 313-314. (Pubitemid 23050919)
16. Gaoni Y, Mechoulam R, (1971). The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. J Am Chem Soc 93: 217-224.
17. Hao S, Avraham Y, Bonne O, Berry EM, (2001). Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine. Pharmacol Biochem Behav 68: 273-281. (Pubitemid 32231189)
18. Häussinger D, Görg B, (2010). Interaction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity. Curr Opin Clin Nutr Metab Care 13: 87-92.
19. Honda H, Ikejima K, Hirose M, Yoshikawa M, Lang T, Enomoto N, et al. (2002). Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver. Hepatology 36: 12-21. (Pubitemid 34700757)
20. Invernizzi R, Carli M, Di Clemente A, Samanin R, (1991). Administration of 8-hydroxy-2-(Di-n-propylamino)tetralin in raphe nuclei dorsalis and medianus reduces serotonin synthesis in the rat brain: differences in potency and regional sensitivity. J Neurochem 56: 243-247. (Pubitemid 21901955)
21. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R, (2009). Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 30: 515-527. Review.
22. Jover R, Rodrigo R, Felipo V, Insausti R, Sáez-Valero J, García-Ayllõn MS, et al. (2006). Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: a model of hepatic encephalopathy in cirrhosis. Hepatology 43: 1257-1266. (Pubitemid 43980104)
23. Kerfoot SM, D'Mello C, Nguyen H, Ajuebor MN, Kubes P, Le T, et al. (2006). TNF-α secreting monocytes are recruited into the brain of cholestatic mice. Hepatology 43: 154-162. (Pubitemid 43733602)
24. van Leeuwen SD, Bonne OB, Avraham Y, Berry EM, (1997). Separation as a new animal model for self-induced weight loss. Physiol Behav 62: 77-81. (Pubitemid 27303767)
25. Magen I, Avraham Y, Berry EM, Mechoulam R, (2008). Endocannabinoids in liver disease and hepatic encephalopathy. Curr Pharm Des 14: 2362-2369. Review.
26. Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM, (2009). Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation. J Hepatol 51: 528-534.
27. 1A receptor activation. Br J Pharmacol 159: 950-957.
28. Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, et al. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 97: 9561-9566. (Pubitemid 30650815)
29. Mallat A, Lotersztajn S, (2008). Cannabinoid receptors as therapeutic targets in the management of liver diseases. Drug News Perspect 21: 363-368. Review.
30. Mazer C, Muneyyirci J, Taheny K, Raio N, Borella A, Whitaker-Azmitia P, (1997). Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible model of neuro developmental disorders with cognitive deficits. Brain Res 760: 68-73. (Pubitemid 27304137)
31. Olton DS, Samuelson RJ, (1976). Remembrance of places passed: spatial memory in rats. J Exp Psychol Anim Behav Process 2: 97-116.
32. Pertwee RG, (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 156: 397-411.
33. Pick CG, Yanai J, (1983). Eight arm maze for mice. Int J Neurosci 21: 63-66. (Pubitemid 14231514)
34. Riggio O, Efrati C, Catalano C, Pediconi F, Mecarelli O, Accornero N, et al. (2005). High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study. Hepatology 42: 1158-1165. (Pubitemid 43112683)
35. 1A receptors. Neurochem Res 30: 1037-1043. (Pubitemid 41570039)
36. Schnur J, Oláh J, Szepesi A, Nagy P, Thorgeirsson SS, (2004). Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice. Eur J Gastroenterol Hepatol 16: 127-133. (Pubitemid 39049647)
37. Shawcross D, Jalan R, (2005). The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci 62: 2295-2304. Review. (Pubitemid 41500545)
38. Shawcross DL, Davies NA, Williams R, Jalan R, (2004). Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40: 247-254. (Pubitemid 38115829)
39. Solter PF, (2005). Clinical pathology approaches to hepatic injury. Toxicol Pathol 33: 9-16. (Pubitemid 40216799)
40. Stahl J, (1963). Studies of the blood ammonia in liver disease. Its diagnostic, prognostic, and therapeutic significance. Ann Intern Med 58: 1-24.
41. Wright G, Jalan R, (2007). Ammonia and inflammation in the pathogenesis of hepatic encephalopathy: pandora's box? Hepatology 46: 291-294. (Pubitemid 47344761)
42. Wu P, Shen Q, Dong S, Xu Z, Tsien JZ, Hu Y, (2008). Calorie restriction ameliorates neurodegenerative phenotypes in forebrain-specific presenilin-1 and presenilin-2 double knockout mice. Neurobiol Aging 29: 1502-1511.
43. Yurdaydin C, Hörtnagl H, Steindl P, Zimmermann C, Pifl C, Singer EA, et al. (1990). Increased serotonergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide-induced acute liver failure. Hepatology 12: 695-700. (Pubitemid 20349253)
44. Yurdaydin C, Herneth AM, Püspök A, Steindl P, Singer E, Ferenci P, (1996). Modulation of hepatic encephalopathy in rats with thioacetamide-induced acute liver failure by serotonin antagonists. Eur J Gastroenterol Hepatol 8: 667-671. (Pubitemid 26241596)
45. Zimmermann C, Ferenci P, Pifl C, Yurdaydin C, Ebner J, Lassmann H, et al. (1989). Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of amino acid-ergic neurotransmission. Hepatology 9: 594-601. (Pubitemid 19094584)