Activity-guided chemo toxic profiling of Cassia occidentalis (CO) seeds: detection of toxic compounds in body fluids of CO-exposed patients and experimental rats.
Our prior studies have shown an association between the deaths of children and consumption of Cassia occidentalis (CO) seeds. However, the chemicals responsible for the CO poisoning are not known. Therefore, the present study was designed to identify the key moieties in CO seeds and their cytotoxicity in rat primary hepatocytes and HepG2 cells. Activity-guided sequential extraction and fractionation of the seeds followed by GC-MS analysis identified the toxic compounds in the CO seeds. These identified compounds were subsequently detected and quantified in blood and urine samples from CO-exposed rats and CO poisoning human study cases. GC-MS analysis of different fractions of methanol extracts of CO seeds revealed the presence of five anthraquinones (AQs), viz. physcion, emodin, rhein, aloe-emodin, and chrysophanol. Interestingly, these AQs were detected in serum and urine samples from the study cases and CO-exposed rats. Cytotoxicity analysis of the above AQs in rat primary hepatocytes and HepG2 cells revealed that rhein is the most toxic moiety, followed by emodin, aloe-emodin, physcion, and chrysophanol. These studies indicate that AQ aglycones are responsible for producing toxicity, which may be associated with symptoms of hepatomyoencephalopathy in CO poisoning cases.
†Food, Drug and Chemical Toxicology Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Post Box 80, Lucknow 226001, India.|∥Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi 110062, India.
Gati Krushna
GK
Panigrahi
‡Analytical Chemistry Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Post Box 80, Lucknow 226001, India.
Ratnasekhar
R
Ch
‡Analytical Chemistry Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Post Box 80, Lucknow 226001, India.
Mohana K R
MK
Mudiam
§Mangla Hospital and Research Centre, Bijnor 246701, Uttar Pradesh India.
Vipin M
VM
Vashishtha
∥Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi 110062, India.
S
S
Raisuddin
†Food, Drug and Chemical Toxicology Group, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, Post Box 80, Lucknow 226001, India.
Mukul
M
Das
D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000737:chemistry* / Q000633:toxicity* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry* / Q000633:toxicity*; D029846:Senna Plant / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship
D010936:Plant Extracts