Chaparral, toxicity

Clark, F., and D. R. Reed. Chaparral-induced toxic hepatitis. California and Texas, 1992. MMWR Morbid Mortal Wkly Rep 1992 41(43) 812-814. Anon. From the Food and Drug Administration. Public Warning about herbal product Chaparral . J Amer Med Ass 1993 269(3) 328. 

Fig. 29.15 Chronic toxic hepatitis after 10 months chaparral ( creosote bush ) automedication. Laparoscopy marked acinar structure, irregular chagreen-like surface (splintered light reflex) and extremely fine fibrosis histology single cell necrosis, slight inflammatory infiltrations and moderate steatosis...

Clark, F. and Reed, R. (1992) Chaparral-induced toxic hepatitis-Califomia and Texas, 1992. Morbidity and Mortality Weekly Reports. 41, 812-814. 

Several cases of hepatotoxicity associated with chaparral use have been described (see Section 16.5). The mechanism of chaparral-associated hepatotoxicity is unknown. It is not known if chaparral is an intrinsic hepatotoxin (i.e., toxic to everyone if the dose is sufficient) or an idiosyncratic hepatotoxin (i.e., toxic only to those who have certain genetically aberrant metabolic pathways or immune system defects). Proposed mechanisms of chaparral-associated hepatotoxicity include (1) inhibition of cyclooxygenase or cytochrome P-450, (2) an immune-mediated reaction, (3) formation of a toxic metabolite, (4) impairment of liver function by phytoestrogens found in chaparral, and (5) cholestatic mechanisms causing impairment of bile formation or excretion. There is likely overlap between the two categories and the various mechanisms. In addition, toxicity may be influenced by age, weight, nutritional status, exposure to other drugs and chemicals, cumulative dose, and preparation (i.e., tea, dried plant parts, etc.) (Sheikh et al., 1997). 

Chaparral has also been associated with cystic renal disease in rats (Grice et al., 1968 Goodman et al., 1970 Evan et al., 1979) and humans (Smith et al., 1994 see Section 16.5). Toxicity studies revealed that cystic nephropathy could be reliably induced in rats fed a 2% by wt concentration of NDGA for 6 wk (Evan et al., 1979). Renal toxicity may stem from the accumulation of theo-quinone metabolite. NDGA is converted to this metabolite in the rat ileum and cecum, absorbed into the bloodstream, and excreted by the kidney, where it is reabsorbed by the epithelial cells of the proximal convoluted tubules. In the rat, tubular changes are thus confined to the tubules in the outer cortex (i.e., the proximal convoluted tubules) (Grice et al., 1968). 

Anonymous. Chaparral-induced toxic hepatitis—California and Texas, 1992. Morbid Mortal Wkly Rep 1992 41 812-4. 

On December 10, 1992, FDA issued a nationwide warning to consumers (FDA Press Release, P92-38) about chaparral, an herbal product derived from the leaves of the creosote bush, because of reports of acute toxic hepatitis after its use. The press release can be found at the FDA Web site, http //www.fda.gov. 

Exposure to wood creosotes appears to be confined to ingestion of plant extracts and dermal contact with the plants. Most of the toxicity data for oral exposure to wood creosotes comes from reports of individuals who ingested plant extracts such as chaparral, an herbal extract prepared by grinding leaves of the creosote bush, or seirogan , a Japanese folk remedy made with wood creosote that is typically taken for stomachaches. 

Hepatic Effects. Icterus, jaundice, abdominal pain, liver failure, acute toxic hepatitis, and elevated serum liver enzymes were among the effects reported in four individuals who repeatedly ingested chaparral capsules (160-1,500 mg chaparral/day) over a period ranging from 6 weeks to 10 months. 

Creosote Bush. Acute toxic hepatitis has been attributed to ingestion of chaparral, an herbal nutritional supplement product derived from the leaves of the creosote bush (Clark and Reed 1992). A 42-year-old man had icterus and jaundice after consuming three 500 mg capsules of chaparral a day for 6 weeks. Serum chemistry tests showed elevated bilirubin, gamma glutamyltranspeptidase (GGT), AST, and lactate dehydrogenase. His illness was diagnosed as hepatic dysfunction secondary to chaparral ingestion. 

Creosote Bush. A 45-year-old woman developed pruritus, probably secondary to chaparral-induced toxic hepatitis, after taking 160 mg/kg/day chaparral for around 2 months (Alderman et al. 1994). 

Creosote Bush. A 45-year-old woman developed fatigue and anorexia after taking 160 mg/kg/day chaparral for around 2 months (Alderman et al. 1994). The patient was diagnosed with chaparral-induced toxic hepatitis. In another report, a 60-year-old woman was hospitalized with a 1-week history of upper quadrant abdominal pain, anorexia, and jaundice (Gordon et al. 1995). The patient had been taking 1-2 capsules of chaparral daily for the past 10 months. The patient developed "flulike syndrome" and increased her chaparral intake to 6 capsules per day 3 weeks before admission. On admission, she was confused her encephalopathy worsened, and she developed seizure activity. The patient was diagnosed with toxic hepatitis secondary to chaparral ingestion. 

Prichard FD, Obermeyer W, Bradlaw J, et al. 1994. Primary rat hepatocyte cultures aid in the chemical identification of toxic chaparral (larreatridentata). In Vitro Cell Develop Biol 30A(3 PT 2) 91-92. 

Reports of acute liver toxicity associated with consumption of chaparral surfaced from 1990 through 1997, leading to the issuance of a warning by the FDA to cease consumption of chaparral (FDA 1992). The American Herbal Products Association (AHPA) initiated a review of four cases (Watt et al. 1994) and found the reported toxicity to be due to idiosyncratic reactions in persons with preexisting liver conditions. The authors concluded, and AHPA recommended in 1995, that products containing chaparral should be labeled with the following cautionary statement Seek advice from... 

Case reports have indicated a correlation between chaparral consumption and liver damage. Amounts of chaparral taken range from 0.3 to 6 g daily, and the duration of use has been from 20 days to "many years," with chaparral being taken as capsules or tablets in most of the cases. The product taken was analyzed in only one case. Although one patient with toxic liver damage required a liver transplant, other cases resolved on cessation of chaparral (lOM 2001). A review of those case reports and associated toxicity studies noted that the severity of liver damage was not related to the dose or duration of chaparral use (lOM 2001). 

Toxic liver damage with elevated aminotransferase levels and joint stiffness in the right hand were reported in a 38-year-old woman who had taken 400 mg chaparral daily for "many years." The patient had a history of drug abuse, alcohol use, and previous exposure to hepatitis C. The reporting authors indicated that chaparral might have potentiated or exacerbated underlying liver disease. The patient eventually required a liver transplant (Sheikh et al. 1997). 

Toxic liver damage with jaundice and abdominal pain was reported in a 41-year-old woman who had taken tablets containing 259 mg/day of chaparral over an 11-week period. The patient retuned to normal after discontinuation of chaparral (Clark and Reed 1992 Sheikh et al. 1997). 

Toxic liver damage with fatigue, jaundice, and dark urine was reported in a 25-year-old man who consumed 3830 mg chaparral capsules daily for 2 to 3 weeks, then 5760 mg daily for 10 weeks. After cessation of chaparral, the patient recovered within 2 weeks (Sheikh et al. 1997). 

Toxic liver damage, confirmed by liver biopsy, with fatigue, jaundice, abdominal pain, light stools, and pruritus was reported in a 57-year-old woman who had consumed 480 mg of chaparral daily for 8 weeks. The woman had used conjugated estrogens in the past (a possible hepato-toxin with persistent effects, but noted as unlikely as the causative agent in the case) (lOM 2001 Sheikh et al. 1997). 

Jaundice with possible toxic liver damage was reported in a 71-year-old man who had been taking an unspecified amount of chaparral capsules daily for an unspecified amount of time. Symptoms of flu-like illness, ascites, and jaundice abated 2 months after cessation of chaparral. The man had a history of alcohol use (14 oz wine daily). One month after restarting chaparral use, the man developed jaundice, ascites, scleral icterus, and nausea. Liver biopsy indicated diffuse necrosis with inflammation, portal tract expansion, mild cholestasis, and mild fibrous septation. A biopsy 3 months later indicated marked improvement (Batchelor et al. 1995). 

Batchelor, W.B., J. Heathcole, and I.R. Wanless. 1995. Chaparral-induced hepatic injury. Am.. Gastroenterol. 90(5) 831-833. Clark, F., and R. Reed. 1992. Chaparral-induced toxic hepatitis California and Texas, 1992. /. Am. Med. Assoc. 268 3295-3298. De Smet, RA.G.M. 1993. Adverse effects of herbal drugs, Volume 2. Berlin Springer. 

Grice, H.C., G. Becking, and T. Goodman. 1968. Toxic properties of nordihydroguaiaretic acid. Food Chem. Toxicol. 6(2) 155. Heron, S., and E. Yamell. 2001. The safety of low-dose Larrea tridentata (DC.) CoviUe (creosote bush or chaparral) A retrospective clinical study. /. Altern. Complement. Afed. 7(2) 175-185. 

---