title: Aqueous extract of Senecio candicans DC induce liver and kidney damage in a sub-chronic oral toxicity study in Wistar rats.
abstract: Senecio candicans DC. (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris, district, Tamil Nadu. The present investigation was carried out to evaluate the sub-chronic toxicity of an aqueous extract of Senecio candicans (AESC) plant in Wistar albino rats. The study was conducted in consideration of the OECD 408 study design (Repeated Dose 90-Day Oral Toxicity Study in Rodents) and the extract was administered via gavage at doses of 250, 500 or 750 mg/kg body weight per day for 90-days. Hematological, biochemical parameters were determined on days 0, 30, 60 and 90 of administration. Animals were euthanized after 90 d treatment and its liver and kidney sections were taken for histological study. The results of sub-chronic study showed significant increase (P < 0.05) in serum uric acid, creatinine, aspartate transaminase (AST) and alanine transaminase (ALP) levels. Histological examination of liver showed mild mononuclear infiltration in the portal trait, enlarged nucleus around the central vein and mild loss of hepatocyte architecture in rats treated with 750 mg/kg of AESC. Histological examination of kidney showed focal interstitial fibrosis, crowding of glomeruli and mild hydropic change with hypercellular glomeruli in rats treated with 750 mg/kg of AESC. However, no remarkable histoarchitectural change in hepatocytes and glomeruli were observed in rats treated with lower concentrations (250 and 500 mg/kg b.w.) of AESC compared to control group animals. The no-observed adverse effect level (NOAEL) of AESC in the present study was 500 mg/kg b.w. Signs of toxic effects are evident from the current study. Although AESC contains low concentrations of PA, findings from this study suggest that regular consumers of herbal remedies derived from this plant may develop kidney and liver toxicity. Further studies on the isolation and characterization of PAs are necessary to determine the safe dose level of the extract for therapeutic use in traditional medicine.
authors.affiliation: Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India; Mushroom Research Centre (MRC), Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia. Electronic address: hariprasath80@um.edu.my.
authors.forename: Hariprasath
authors.initials: H
authors.lastname: Lakshmanan
authors.affiliation: Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India; Mushroom Research Centre (MRC), Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Jegadeesh
authors.initials: J
authors.lastname: Raman
authors.affiliation: Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India; Department of Crop Science, Tshwane University of Technology, Pretoria Campus (West), Pretoria, 0001, South Africa.
authors.forename: Arjun
authors.initials: A
authors.lastname: Pandian
authors.affiliation: Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, Tamil Nadu, India.
authors.forename: Kumaresan
authors.initials: K
authors.lastname: Kuppamuthu
authors.affiliation: Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India.
authors.forename: Raaman
authors.initials: R
authors.lastname: Nanjian
authors.affiliation: Mushroom Research Centre (MRC), Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Vikineswary
authors.initials: V
authors.lastname: Sabaratam
authors.affiliation: Mushroom Research Centre (MRC), Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia; Department of Anatomy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Murali
authors.initials: M
authors.lastname: Naidu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D010946:Plants, Medicinal; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D017208:Rats, Wistar; D018570:Risk Assessment; D012674:Senecio / Q000737:chemistry / Q000633:toxicity*; D013997:Time Factors; D059550:Toxicity Tests, Subchronic
chemical_list: D000897:Anti-Ulcer Agents; D015415:Biomarkers; D010936:Plant Extracts; D011763:Pyrrolizidine Alkaloids
keywords: Albino rats; Aqueous extract; Pyrrolizidine alkaloids; Safety evaluation; Senecio candicans; Sub-chronic toxicity