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TABLE E Nordihydroguaiaretic Acid (NDGA): Summary of Animal Studies

Species/Study Design

Results and Conclusions

Acute toxicity studies, gavage or oral administration

Toxicity Data






5.5 g/kg

Gavage (Lehman et al., 1951)



4 g/kg

Gavage (Lehman et al., 1951)



0.1–0.8 g/kg

i.p. (Fujii et al., 1970; Kozubik et al., 1993; Madrigal-Bujaidar et al., 1998)


Guinea pig 0.8 g/kg

Gavage (Lehman et al., 1951)

Rats (male, S/D), NDGA (single dose at 25 or 50 mg/kg body weight, gavage), ± indomethacin mucosa (20 mg/kg body weight, gavage), animals were sacrificed 4 hr later

NDGA enhanced indomethacin-induced mast cell degranulation in gastric

NDGA increased prostanoid activity in gastric glandular mucosa

With NDGA pretreatment, indomethacin-induced lesions in the gastric mucosa were more severe; this is a possible cytotoxic effect (Cho and Ogle, 1987)

Acute toxicity studies, other routes of administration

Rats (Wistar Albino), NDGA (1 dose at 10 μg/kg body weight, i.v.)

In a model of ischemia reperfusion injury to the liver, rats were given NDGA 5 min before reperfusion (± iloprost, 25 μg/kg i.v., given just before warm ischemia)

By histopathologic examination, liver damage was more extensive in the rats treated with NDGA compared with the control (saline-injected) animals (Okboy et al., 1992)

Mice (female, CD1), NDGA (50 mg/kg body weight, i.v.)

Pharmacokinetic analysis (using M4NDGA as a standard):

Peak plasma concentration = 14 μg/mL

Exposure (AUC) = 248 μg/mL/min

Clearance = 202 mL/(min/kg)

Volume of distribution = 3.4 L/kg

Half-life in 1st compartment = 30 min

Half-life in 2nd compartment = 135 min

NDGA appears to follow a 2-compartment pharmacokinetic model (Lambert et al., 2001)

Mice (male, CBA), NDGA (2 doses, 2-h apart, 50 mg/kg body weight, i.p.)

At 2 wk after treatments (NDGA, galactosamine, and endotoxin), histological examination of liver showed small foci of necrosis adjacent to areas of infiltration of inflammatory cells; some of this hepatic damage was due to endotoxin administration (Parry, 1993)

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