28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

Abstract

Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg.

Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis

“…In addition, we did not determine the most effective dose and safe dose range of ATG. Previous studies showed the least observed adverse effect was induced by 12 mg/kg daily ATG exposure for successive 28 days in rats (Tan et al, 2018). In the present study, no mortality and obvious clinical signs of ATG-related toxicity were observed in animals treated with ATG (3 mg/kg/d) alone during the study period (28 days, data shown in Supplementary Figure S1), suggesting that ATG may be safe to treat PQ-induced fibrosis.…”

Toxicological Profile of Nanostructured Bone Substitute Based on Hydroxyapatite and Poly(lactide-co-glycolide) after Subchronic Oral Exposure of Rats

“…Accordingly, the liver is chosen due to its vital role in organism being reflected by its physiological functions, synthesis and detoxification of various metabolites. In other words, any lesions caused by drugs, chemicals, and pathological status could interrupt its functions [27]. The ALT level, which is found primarily in the liver, and is released into the circulation from damaged hepatocytes, was slightly higher in the experimental group, while the AST level, found in the erythrocytes, myocytes, and kidney cells also, was higher in the control, without significant differences [27].…”

“…In other words, any lesions caused by drugs, chemicals, and pathological status could interrupt its functions [27]. The ALT level, which is found primarily in the liver, and is released into the circulation from damaged hepatocytes, was slightly higher in the experimental group, while the AST level, found in the erythrocytes, myocytes, and kidney cells also, was higher in the control, without significant differences [27]. Similar results of biocompatibility investigation of Mg-Zn materials were reported, with the assertion that there was no change in the hepatocyte architecture and morphology of liver lobules [28].…”

Subacute toxicological evaluation of AT‑533 and AT‑533 gel in Sprague‑Dawley rats

“…The hematopoietic system is considered to be the most sensitive target for toxicities, and its index of physiological and pathological status is direct evidence for toxicology studies (32). Hematological analysis data suggested that, except for the WBC, NE and PLT counts, other hematological parameters showed no toxicologically significant differences.…”