Mechanism of hepatotoxicity due to black cohosh (Cimicifuga racemosa): Histological, immunohistochemical and electron microscopy analysis of two liver biopsies with clinical correlation

Troxis necrosis, a novel mechanism for drug-induced hepatitis secondary to immunomodulatory therapy

“…Through immunohistochemistry and electron microscopy, we have previously demonstrated that there is an infiltration of lymphocytes in the liver parenchyma simulating lobular hepatitis (Wang et al, 2001; French & Enbom, 2014; Enbom et al, 2014; Chen et al, 2010). Ultra structurally, the lymphocytes and hepatocytes formed focal synaptic connections on the cell membrane.…”

“…Cases of acute liver injury mediated by troxis necrosis have been reported in patients with Hepatitis B and C, non-alcoholic steatohepatitis (NASH), primary biliary cirrhosis (PBC), and autoimmune hepatitis (Wang et al, 2001; French & Enbom, 2014; Enbom et al, 2014; Chen et al, 2010). In drug-implicated troxis necrosis, some of the reported cases to date have been linked to the consumption of herbal supplement such as Hydroxycut and Herbalife products (Enbom et al, 2014; Chen et al, 2010).…”

“…In drug-implicated troxis necrosis, some of the reported cases to date have been linked to the consumption of herbal supplement such as Hydroxycut and Herbalife products (Enbom et al, 2014; Chen et al, 2010). Literature search yielded 7 previously reported cases of drug-induced hepatitis mediated by troxis necrosis (Wang et al, 2001; Enbom et al, 2014; Chen et al, 2010). In this report, the implicated drugs are three immune modulatory medications used to treat systemic lupus erythematosus, including the experimental drug anti-TWEAK monoclonal antibody.…”

Pre-clinical in vitro and in vivo safety evaluation of Cimicifuga heracleifolia

“…A North American species, C. racemosa has long been used to treat female reproductive disorders both in Asia and Europe . Along with significant elevations of ALT, liver biopsies of female patients who developed acute submassive liver necrosis following consumption of C. racemosa showed heavy lymphocytic infiltration of the portal tracts and hepatocytes (Enbom et al, 2014). Interestingly, the hepatotoxic potential of the CH extract (serum ALT activity rise and increased liver weight) in the 13-week repeat-dose oral toxicity study using rats was found only in females although the incidences of moderate focal inflammations in liver tissues of female rats following the treatment of the CH extract at doses of 667 (3/10) and 2000 mg/kg (1/10) showed very slight difference in comparison to the controls (0/10) in the present study.…”

“…It has been reported that C. racemosa induced the acute liver injury (Enbom et al, 2014;Muqeet Adnan et al, 2014;NIDDK, 2015). However, the CH extract also had little comprehensive toxicological information from the toxicity studies that have been carried out under the Good Laboratory Practice (GLP) regulations.…”